Aim To investigate the effect of icariin(ICA)on chronic ulcerative colitis(UC)in mice.Methods Male SPF-grade C57BL/6J mice were ran-domly divided into the control group,model group,low-dose ICA group,and high-dose ICA group.Except for the control group,the rest of the mice were established as chronic UC models.Expressions of tight junction proteins,inflammatory factors,fibrosis markers,macro-phage markers,and MAPK signaling pathways in the colonic epithelium of each group were determined by Western blot,qPCR,immunohistochemistry;the degree of intestinal damage and fibrosis was detected by HE and Masson staining;the co-localization of different macrophage markers with related factors was examined by immunofluorescence.Results Treatment of ICA significantly improved the general condition of chronic UC mice,decreased the infiltration of M1-type macro-phages and the secretion of pro-inflammatory factors,inhibited the MAPK signaling pathway,reduced the co-localization expression of M1-type macrophages with the MAPK signaling pathway,and downregulated the infiltration of M2-type macrophages and the secretion of pro-fibrotic factors in the colon.Conclusion ICA mitigates the inflammatory damage and fibrosis of colon in chronic UC mice.

Aim To investigate the effect of icariin(ICA)on chronic ulcerative colitis(UC)in mice.Methods Male SPF-grade C57BL/6J mice were ran-domly divided into the control group,model group,low-dose ICA group,and high-dose ICA group.Except for the control group,the rest of the mice were established as chronic UC models.Expressions of tight junction proteins,inflammatory factors,fibrosis markers,macro-phage markers,and MAPK signaling pathways in the colonic epithelium of each group were determined by Western blot,qPCR,immunohistochemistry;the degree of intestinal damage and fibrosis was detected by HE and Masson staining;the co-localization of different macrophage markers with related factors was examined by immunofluorescence.Results Treatment of ICA significantly improved the general condition of chronic UC mice,decreased the infiltration of M1-type macro-phages and the secretion of pro-inflammatory factors,inhibited the MAPK signaling pathway,reduced the co-localization expression of M1-type macrophages with the MAPK signaling pathway,and downregulated the infiltration of M2-type macrophages and the secretion of pro-fibrotic factors in the colon.Conclusion ICA mitigates the inflammatory damage and fibrosis of colon in chronic UC mice.

Adult ; Cesarean Section/statistics & numerical data* ; China/epidemiology* ; Female ; Humans ; Pregnancy ; Pregnancy Outcome/epidemiology* ; Risk Factors ; Trial of Labor ; Young Adult

OBJECTIVE: To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD). METHODS: The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed. RESULTS: Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment. CONCLUSION The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.
Amphotericin B ; Antifungal Agents ; Child ; Hematologic Diseases ; etiology ; Humans ; Invasive Fungal Infections ; complications ; Retrospective Studies

OBJECTIVETo prospectively study the correlation BKV with the occurrence and development of late onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).

METHODSThe clinical data of a total of 276 patients with allo-HSCT in our department between January 1998 and March 2016 were analyzed ratrospectvely. Quantitative Real-time PCR assay was used to prospectively monitor the BKV DNA load of the urine and plasma for 23 patients accepting allo-HSCT from August 2015 to March 2016.

RESULTSLOHC(24.28%) occurred in 67 of 276 cases with allo-HSCT. Univariate analysis showed that age older than 6 years, different diseases, unrelated donor, pretreatment with BU, Ⅲ-Ⅳ aGVHD significantly correlated with LOHC. Multivariate analysis demonstrated that age older than 6 years (P<0.01), pretreatment with BU(P<0.05), and aGVHD of grade Ⅲ-Ⅳ （P= 0.011） were the independent risk factors for LOHC. Among 23 patients after allo-HSTC, 10 of which were positive of urine BKV, and LOHC occurred in 6 cases. The positive rate of urine BKV (85.7%)in group LOHC was significantly higher than that in the group LOHC(25.0%）(χ=5.043, P<0.01). The incidence of LOHC positively correlated with the positive rate of BKV (r=0.564, P<0.01), and the severity of LOHC positively correlated with urinary BKV load (r = 0.502, P<0.01). And 5 of 6 petriatic patients with LOHC had aGVHD. All of them were subject to the strengthened antiviral treatment, and 4 of them accepted intensive immunosuppression therapy.

CONCLUSIONAge ≥6 years old, precenditioning regieme with BU and aGVHD of grade Ⅲ-Ⅳ are independent risk factors for LOHC after allo-HSCT, the positive rate of urine BKV load positively correlates with the severity of LOHC after allo-HSCT.

Child ; Cystitis ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hemorrhage ; Humans ; Incidence ; Risk Factors ; Transplantation, Homologous

OBJECTIVETo study the curative effect and safety of menchymal stem cell infusion in treatment of children with refractory late-onset hemorrhagic cystitis(LOHC) after allogeneic HSCT.

METHODSThirty cases of children with refractory LOHC after allo-HSCT in our department between December 2010 and July 2016 were analyzed retrospectively, out of 30 cases 7 received MSC treatment. The used MSC of all were four-to-five generation MSC from bone marrows of third party donors, and were infused into patients with (1.87±0.456)×10/kg MSCs once a week (1-4 times in total) until the hematuria and odynuria symptoms being improved. To observe whether unfavorable reactions occurred after MSC treatment, the patients accepted daily physical examination and regular assistant examination. The cytokine levels were also measured and dynamically detected in 2 cases before and after MSC treatment.

RESULTSIn 30 children with refractory LOHC, the hematuria difficultly reached the remission after routine hydration, alkalizing and antiviral therapy, Among 25 cases who were received methylprednisolone, MTX and CTX therapy, 7 cases received MSC infusion for 1-4 times with dose of (1.87±0.456)×10/(kg·time) as a result, 7 cases of LOHC were cured. The TNF-α and IL-2R levels in 2 cases progressively decreased after MSC infusion, no occurence of fever, rash, embolism and so on were found in 7 cases received MSC infusion; the BKV detection showed that the viral load did not increase; the leukemia relapse or secondary cancer did not occure.

CONCLUSIONThe MSC treatment is safe and effective for refractory LOHC after allo-HSCT.

Child ; Cystitis ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Mesenchymal Stem Cell Transplantation ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo investigate the efficacy and safety of NOPHO-AML 2004 chemotherapy regimen for treatment of children with acute myelocytic leukemia(non-M3).

METHODSThirty-three patients aged 1-13 with acute myelocytic leukemia (non-M3) were diagnosed from January 2013 to June 2017. FAB typing showed that 1 case in M0, 4 cases in M1, 12 cases in M2, 5 cases in M4, 8 cases in M5, 1 case in M6, and 2 cases in M7; Risk stratification showed that: 19 cases in standard risk, and 14 cases in high risk. All patients were treated with NOPHO-AML 2004 chemotherapy regimen. SPSS 22.0 software was used, the Kaplan-Meier survival analysis method and Cox regression model were used for statistical analysis.

RESULTSIn the first course of treatment (AIET), among 33 child patients there were 27 cases with complete remission, and 5 cases with non-remission, thus the remission rate was 81.8%. Out of the 5 child patients without remission, 4 cases reached to the complete remission after the second course (AM), and 1 case did not remission, thus the total remission rate was 96.9%.9 cases (27.3%) underwent bone marrow recurrence and the median recurrence time was 30 months after complete continuous remission. Univariate analysis showed that age and erythrocyte transfusion frequency were significant factors to affect the early treatment response; the multiple Cox regression analysis showed that: age >7, MRD positive, erythrocyte transfusion >4 times and poor response to early treatment were independent risk factors for recurrence; Allogeneic hematopoietic stem cell transplantation(HSCT) in 8 high-risk children received enhanced chemotherapy had better efficacy as compared with the chemotherapy alone. The 3-year event-free survival rate was 59.9%, and 3-year overall survival rate was 69.2%. 33 children patients experienced varying degrees of infection and myelosuppression, or drug-related gastrointestinal reactions and allergic reactions, patients were tolerable to these side reactions after active symptomatic treatment.

CONCLUSIONNOPHO-AML 2004 chemotherapy regimen has high response rate and good tolerance, early treatment response is an important factor influencing prognosis. Age and repeated red blood cell infusions are the important factors influencing the prognosis, which promote bone marrow recurrence in AML children. For the children suffered from clinical high-risk AML, the NOPHO-AML 2004 chemotherapy regimen combined with HSCT can improve the prognosis of patients.

Adolescent ; Child ; Child, Preschool ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myeloid, Acute ; Prognosis ; Remission Induction ; Treatment Outcome

Discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas (APAs) with distinct clinical presentations and pathological features. Catenin β1 (CTNNB1) mutation in APAs has been recently described and discussed in the literature. However, significant knowledge gaps still remain regarding the prevalence, clinical characteristics, pathophysiology, and outcomes in APA patients harboring CTNNB1 mutations. Aberrant activation of the Wnt/β-catenin signaling pathway will further modulate tumorigenesis. We also discuss the recent knowledge of CTNNB1 mutation in adrenal adenomas.
Adenoma* ; Aldosterone* ; Carcinogenesis ; Humans ; Prevalence

OBJECTIVE To investigate the mechanisms of Triptolide in ER(+) human breast cancer MCF-7 cells from CYP19.METHODS The inhibition of the MCF-7 cells influenced by Triptolide and Letrozole was analyzed respectively by MTT assays.The aromatase levels were measured by Western blot.The CYP19 gene was observed by RT-PCR.The MCF-7 cells of high and low expression CYP19 gene were transfacted.It's CYP-19 and downstream channel gene JNK,p-38 and ERK were observed by Western blot.RESULTS Triptolide displayed a dose-and time-dependent inhibition of the MCF-7 cells.It inhibited the aromatase and CYP19.The expression of CYP19 in MCF-7 cells of low expression CYP19 was significantly decreased.Phosphorylation of JNK,p38 and ERK was inhibited too.CONCLUSION Triptolide inhibit MCF-7 cells not only via inhibition aromatase,but also blocking Ras-Raf-MAPK-ERK enzyme.

The present study was aimed to investigate the role of necroptosis in the pathogenesis of acute respiratory distress syndrome (ARDS). The rat model of ARDS was induced by intravenous injection of oleic acid (OA), and observed for 4 h. The lung injury was evaluated by arterial blood gas, lung wet-dry weight ratio (W/D) and histological analyses. Simultaneously, bronchoalveolar lavage fluid (BALF) was collected for total and differential cell analysis and total protein determination. Tumor necrosis factor alpha (TNF-α) level in BALF was determined with a rat TNF-α ELISA kit. Expressions of receptor interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL) in lung tissue were determined by Western blot and immunohistochemical staining. The interaction between RIPK1 and RIPK3 was explored by immunoprecipitation. The results showed that, compared with those in control group, total white blood cells count (WBC), polymorphonuclear percentage (PMN%), total protein concentration, TNF-α level in BALF, W/D, and the alveolar-arterial oxygen tension difference (P(A-a)O) in OA group were significantly increased at 4 h after OA injection. Western blot and immunostaining further showed remarkably increased expressions of RIPK1, RIPK3 and MLKL in lung tissue from OA group. Additionally, immunoprecipitation results indicated an enforced interaction between RIPK1 and RIPK3 in OA group. Collectively, the TNF-α level in BALF and the RIPK1-RIPK3-MLKL signaling pathway in lung tissue were found to be upregulated and activated with the process of ARDS. These findings implicate that RIPK1/RIPK3-mediated necroptosis plays a possible role in the pathogenesis of ARDS, which may provide a new idea to develop novel drugs for the therapy of ARDS.
Acute Disease ; Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Lung Diseases ; Necrosis ; Oleic Acid ; Rats ; Receptor-Interacting Protein Serine-Threonine Kinases ; Respiration Disorders ; Signal Transduction ; Tumor Necrosis Factor-alpha