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Objective To investigate the effects of Polygonatum kingianum on wound healing and nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in diabetic skin injury rats.Methods Diabetic rat models were established and 48 rats were randomly divided into model group,sitagliptin group(10 mg·kg-1),Polygonatum kingianum water extract low dose group(2 g·kg-1),Polygonatum kingianum water extract high dose group(8 g·kg-1)and Polygonatum Kingianum alcohol extract low and high dose group(2 g·kg-1 and 8 g·kg-1).8 in each group;Another control group was set up.After 4 weeks of intragastric administration,all rats established back skin wounds,and continued to be administered for 14 days after operation.At the end of the experiment,the rats were killed,and blood glucose,glycosylated hemoglobin(GHb),plasma levels of H2O2,MDA,SOD,GSH and wound margin skin tissue T-AOC,SOD,MDA levels were measured.The relative expression of Nrf2 and HO-1 mRNA in wound margin skin tissue was measured by fluorescence quantitative method.Results Compared with the model group,the levels of SOD and GSH in plasma and the relative expressions of Nrf2 and HO-1 mRNA in wound margin skin tissue in the low and high dose groups of ethanol extract of Polygonatum kingianum,and the low and high dose groups of water extract of Polygonatum kingianum were increased(P<0.01,P<0.001).The levels of glycosylated hemoglobin(GHb)in plasma and MDA in wound margin tissue were decreased(P<0.05,P<0.01,P<0.001).The level of T-AOC in the high dose group was increased(P<0.01).The SOD level of skin tissue in the low dose group of Polygonatum kingianum water extract was increased(P<0.01),and the level of H2O2 in the low dose group was decreased(P<0.01).Conclusion Polygonatum canaliculatum can up-regulate Nrf2/HO-1 signaling pathway,regulate excessive oxidative stress,and promote wound healing.
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Objective:To explore the effects of hospital-to-community model-based case management on outcomes and life quality of patients with atrial fibrillation.Methods:By convience sampling method, a total of 90 cases of atrial fibrillation patients admitted to Changzhou Second People′s Hospital from January 2019 to May 2020 were randomly divided into control group and experimental group, with 45 cases in each group. The patients in the control group received routine nursing care, the experimental group implemented hospital-to-community model-based case management. The beliefs about medicine, medication compliance, quality of life and readmissions of cardiovascular events were compared between 2 groups before and 6 months after intervention.Results:Finally, 41 cases were included in the experimental group and 38 cases in the control group. Before intervention, there were no significant differences in various indexes between the two groups ( P>0.05). After 6 months of intervention, the scores of specific-necessity in Beliefs about Medicines Questionnaire-Specific (BMQ-Specific) and Morisky Medication Adherence Scale-8 (MMAS-8) were (16.98 ± 4.22) and (7.15 ± 0.69) points in the experimental group, higher than in the control group (14.95 ± 4.33) and (6.32 ± 1.07) points; the scores of specific-concerns in BMQ-Specific were (6.83 ± 1.91)points in the experimental group, lower than in the control group (8.42 ± 2.73) points. The differences were statistically significant ( t = 2.11, 4.07, 2.98, all P<0.05); the scores of physical function, role-physical, pain, general health, mental health dimensions and total scores in SF-36 were (80.37 ± 3.46), (46.63 ± 14.54), (90.37 ± 5.78), (70.07 ± 9.98), (84.20 ± 8.73) and (584.88 ± 25.71) points in the experimental group, higher than in the control group (70.13 ± 11.20), (37.34 ± 10.25), (83.37 ± 6.89), (59.55 ± 7.98), (77.58 ± 9.09) and (533.87 ± 31.62) points, the differences were statistically significant ( t values were 3.30-7.89, all P<0.05). At 6 months after discharge, the re-admission of cardiovascular events were 5 cases (12.2%) in the experimental group and 12 cases (31.6%) in the control group, the difference was statistically significant ( χ2=4.74, P<0.05). Conclusions:Hospital-to-community model-based case management can effectively promote beliefs about medicine and medication compliance, improve quality of life and decrease re-admission of cardiovascular events of patients with atrial fibrillation.
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Objective:To explore the optimum time of ambulation of atrial fibrillation patients after radiofrequency ablation, to provide basis for patients' early postoperative rehabilitation.Methods:By convenient sampling method, a total of 120 patients with atrial fibrillation after radiofrequency ablation were collected at Yanghu Branch and City Branch of Changzhou Second People's Hospital from January 2020 to May 2021. They were divided into the early group, middle group and late group according to the random number table method, each group were 40 cases. All patients received routine postoperative intervention, the time of ambulation were 4, 6 and 12 h after operation in the early group, middle group and late group, respectively. The complication rate within 24 h after operation was compared among the three groups, and the comfort level of the three groups at 24, 48 and 72 h after operation was evaluated with Comfort Status Scale (GCQ).Results:Finally, 111 patients were included, including 37 in the early group, 38 in the middle group and 36 in the late group. There was no significant difference in the incidence of bleeding or hematoma, urinary retention, lumbago within 24 h after operation among the three groups ( P>0.05). The incidence of postural hypotension within 24 h after operation in the early group was 2.7% (1/37), which was lower than 21.1% (7/38) and 25.0% (9/36) in the middle and late groups, with a statistically significant difference ( χ2=4.86, 7.67, both P<0.05). At 48 and 72 h after operation, the scores of physiological dimension, psychological dimension and the total score of GCQ in the early group were (20.68 ± 3.07), (22.54 ± 3.35), (81.68 ± 6.11) and (22.54 ± 3.73), (24.38 ± 2.49), (84.92 ± 6.37), higher than those in the middle group (19.16 ± 2.19), (21.32 ± 2.27), (78.24 ± 5.58), (20.93 ± 2.85), (22.32 ± 2.04), (81.66 ± 6.56), and those in the late group (18.44 ± 1.50) (21.31 ± 1.99), (78.06 ± 4.32), (20.89 ± 2.25), (21.58 ± 1.86), (80.28 ± 6.44), the differences were statistically significant ( t values were 2.19-4.15, all P<0.05). Conclusions:Ambulation at 4 h after operation does not increase peripheral vascular complications, but can reduce the incidence of postural hypotension and improve the comfort of patients with atrial fibrillation after radiofrequency ablation.
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OBJECTIVES@#To investigate the risk factors as well as their impact on patients' survival of central nervous system (CNS) complications following allogeneic hematopoietic stem cell transplantation (HSCT).@*METHODS@#All relevant clinical data from a total of 323 patients, who underwent allogeneic HSCT in Xiangya Hospital of Central South University from September 2016 to September 2019, were retrospectively reviewed in this study. The complications' occurrence time, common symptoms and some other clinical data of the patients who developed CNS complications were analyzed descriptively. The risk factors for CNS complications following allogeneic HSCT were analyzed through univariate and multivariate analysis. And the survival analysis was conducted as well.@*RESULTS@#Among the 323 patients who underwent allogeneic HSCT, 32 patients developed CNS complications. These complications occurred in these patients at a median of 32 (range from -1 to 584) d after transplantation. Common symptoms were disturbance of consciousness (78.1%), convulsion (59.4%), and headache (12.5%). Univariate analysis showed that there were significant differences in neutrophil engraftment, platelet (PLT) engraftment, serum cytomegalovirus (CMV) DNA positive, combined with acute graft-versus-host disease (aGVHD), donor selection (@*CONCLUSIONS@#The delay or the failure of PLT engraftment and combined with aGVHD are the risk factors for CNS complications. The facts indicate that we should prevent CNS complications when patients who underwent allogeneic HSCT with the delay or the failure of PLT engraftment or aGVHD. Compared with non-CNS complication group, patients who developed CNS complications usually have poor prognosis.
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Humans , Central Nervous System , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Risk FactorsABSTRACT
Chronic graft-versus-host disease (cGVHD) is a major cause for late non-relapse-related death in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and seriously affects their quality of life. cGVHD may involve many systems in the whole body and its clinical manifestations are similar to autoimmune diseases, and the main pathology is fibrosis. The therapeutic regimen based on glucocorticoids remains as the first-line treatment for cGVHD. Since long-term and high-dose application of glucocorticoids result in serious complications, along with the appearance of steroid-resistant and recurrence/refractory cGVHD, conventional immune suppressive agents have limited clinical efficacy. With the progress in understanding of the pathological mechanisms for cGVHD, many treatments, such as depletion of alloreactive T cells, B-cell depletion, preventing B cell differentiation, targeting the B-cell receptor signaling pathway, inhibition of cytokine receptor-mediated signaling, enhancement of Tregs in vivo, adoptive Tregs therapy, facilitating Tregs reconstitution, and anti-fibrosis therapy, have been supported by clinical and preclinical results.
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Humans , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Quality of Life , Transplantation, Homologous , Treatment OutcomeABSTRACT
To study the molecular mechanism for DNA hypomethylation of STAT3 promoter in CD4+ T cells from acute graft-versus-host disease (aGVHD) patients. Methods: We collected CD4+ T cells from peripheral blood of 42 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-identical sibling donors. GADD45A expression level in CD4+ T cells was measured by real-time PCR and Western blot. The binding level between HMGB1 and GADD45A in CD4+ T cells was analyzed by co-immunoprecipitation, while the binding levels of HMGB1/GADD45A with STAT3 promoter were detected by chromatin immunoprecipitation-quantitative real-time PCR (ChIP-qPCR). After overexpression of HMGB1 and knockdown of GADD45A in normal CD4+ T cells, STAT3 expression and DNA methylation were measured by Western blot and bisulfite sequencing PCR, respectively. Results: GADD45A expression was significantly up-regulated in patients with aGVHD compared with that in the patients without aGVHD. More HMGB1-GADD45A complexes were found in CD4+ T cells from patients with aGVHD compared with that in patients without aGVHD. The bindings of HMGB1/GADD45A with STAT3 promoter were significantly increased, and the binding levels of HMGB1/GADD45A were negatively correlated with STAT3 promoter DNA methylation. The expression of STAT3 was significantly reduced and the DNA methylation of STAT3 promoter was significantly increased in CD4+ T cells with overexpression of HMGB1 and knockdown of GADD45A compared with CD4+ T cells only with overexpression of HMGB1. Conclusion: The increased expression of HMGB1/GADD45A plays an importent role in STAT3 promoter DNA hypomethylation, thereby promoting STAT3 expression in CD4+ T cells from aGVHD patients.
Subject(s)
Humans , CD4-Positive T-Lymphocytes , Cell Cycle Proteins , Metabolism , DNA Demethylation , Gene Expression Regulation , Genetics , Graft vs Host Disease , Genetics , HMGB1 Protein , Metabolism , Hematopoietic Stem Cell Transplantation , Nuclear Proteins , Metabolism , Promoter Regions, Genetic , Genetics , STAT3 Transcription Factor , Genetics , MetabolismABSTRACT
To study the relationship between acute graft-versus-host disease (aGVHD) and the SIRT1 expression in peripheral blood CD4+T cells from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: We collected 40 patients who underwent allo-HSCT from human leukocyte antigen (HLA)-identical sibling donors. SIRT1 expression level in CD4+T cells was measured by real-time PCR and Western blot. Acetylation and phosphorylation of STAT3 in CD4+T cells were detected by Western blot. The binding level between SIRT1 and STAT3 in CD4+T cells was analyzed by co-immunoprecipitation and Western blot. Over-expression of SIRT1 in aGVHD CD4+T cells, as well as STAT3 acetylation and phosphorylation were measured by Western blot. The mRNA levels of RORγt, IL-17A, IL-17F related to Th17 were detected by real-time PCR. Results: SIRT1 expression was significantly down-regulated, while STAT3 expression, acetylation and phosphorylation levels were significantly up-regulated in patients with aGVHD compared with patients without aGVHD. The STAT3 acetylation was positively correlated with STAT3 phosphorylation (r=0.69, P<0.01). Less SIRT1-STAT3 complexes were found in CD4+T cells from patients with aGVHD compared with patients without aGVHD. After SIRT1 over-expression in aGVHD CD4+T cells, the STAT3 acetylation and phosphorylation, and the expression of RORγt, IL-17A, and IL-17F related to Th17 were significantly down-regulated (P<0.05). Conclusion: SIRT1 deficiency in CD4+T cells plays a crucial role in up-regulation of STAT3 acetylation and phosphorylation, the increase of Th17 related gene expression, and induction of aGVHD after allogeneic hematopoietic stem cell transplantation.
Subject(s)
Humans , Acute Disease , CD4-Positive T-Lymphocytes , Metabolism , Down-Regulation , Graft vs Host Disease , Metabolism , Hematopoietic Stem Cell Transplantation , Histocompatibility Antigens Class I , Interleukin-17 , Metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3 , Metabolism , STAT3 Transcription Factor , Metabolism , Sirtuin 1 , Metabolism , Transplantation, Homologous , Up-RegulationABSTRACT
Objective:To study the relationship between acute graft versus host disease (aGVHD) and the methylation status of the STAT3 promoter in peripheral blood CD4+ T cells from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:We collected 40 patients who underwent allo-HSCT from HLA-identical sibling donors.Serum IL-10,TGF-β1,IL-17A and IL-17F levels were detected by ELISA.Foxp3 cytotoxic T-lymphocyte-associated protein 4 (CTLA4),IL-10,TG F-β 1,RO Rγt,IL-17A and IL-17F mRNA levels in CD4+ T cells were measured by real-time PCR.STAT3 expression levels were detected by real-time PCR and Western blot,and promoter DNA methylation was analyzed by bisulfite sequencing PCR (BSP).Results:IL-10 and TGF-β1 levels were significantly down-regulated,while IL-17A and IL-17F levels were significantly up-regulated in patients with aGVHD compared with patients without aGVHD.Foxp3,CTLA4,IL-10,TGF-β1 mRNA levels were significantly down-regulated,while RORγt,IL-17A,IL-17F mRNA levels were significantly up-regulated in patients with aGVHD compared with patients without aGVHD.STAT3 expression was increased,while STAT3 promoter DNA was hypomethylated in patients with aGVHD compared with those without aGVHD.The STAT3 mRNA level was negatively correlated with STAT3 promoter DNA methylation.Conclusion:The imbalance of Treg/fh17 in CD4+ T cells from patients after allo-HSCT is a key factor for triggering aGVHD,and the DNA hypomethylation of STAT3 promoter could promote its expression in CD4+ T cells and contribute to the imbalance.
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OBJECTIVE@#To screen aptamers binding CD33+/CD34- cells from patients with acute myeloblastic leukemia M2 subtype (AML-M2).@*METHODS@#CD33+/CD34- cells from patients with AML-M2 were taken as targeted cells, CD33+/ CD34- cells from normal people were taken as anti-selecting cells, and aptamers in the single strand deoxyribonucleic acid (ssDNA) library were then selected repeatedly by cell-systematic evolution of ligands by exponential enrichment (C-SELEX) technology, and amplified by polymerase chain reaction (PCR) to generate sub-ssDNA library. During the experiment, PCR amplification with fluorescently labeled primer and flow cytometry were performed to analyze the aptamers'enrichment of sub-library, and the final round product of the sub-ssDNA library was cloned. After the sequencing, the primary and secondary structures of the aptamers were analyzed.@*RESULTS@#Electrophoresis indicated that the product of PCR amplification for each round subssDNA library was able to see a clear DNA band in the agarose gel. After 13 rounds of screening, the fluorescence intensity of the sub-ssDNA library binding the cells ranged from 2.14% to 51.12%, reaching a steady state at the 13th round. A total of 30 clones were selected and sequenced, 22 of which contained 1 of the 4 conserved sequences of AAGTA, TATCT, AGATG and AAATT in their primary structure, but the remained eight aptamers contained none of the conserved sequence. Secondary structure analysis indicated that four stem-loops and loop simulation convex structures existed in the aptamers.@*CONCLUSION@#C-SELEX technology can be used to screen the aptamers binding primary cells from patients with leukemia. The aptamers selected from the CD33+/CD34- cells from the patients of AML-M2 subtype might be used for the diagnosis and treatment for leukemia.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antigens, CD34 , Genetics , Allergy and Immunology , Antigens, Differentiation, Myelomonocytic , Genetics , Allergy and Immunology , Aptamers, Nucleotide , Genetics , Metabolism , DNA, Single-Stranded , Genetics , Leukemia, Myeloid, Acute , Genetics , Allergy and Immunology , SELEX Aptamer Technique , Sialic Acid Binding Ig-like Lectin 3 , Genetics , Allergy and ImmunologyABSTRACT
OBJECTIVE@#To study the efficacy of allogeneic hemotopoietic stem cell transplantation (allo-HSCT) for hematological malignancy.@*METHODS@#A total of 104 patients with hematological malignancy, who underwent allo-HSCT in Xiangya Hospital from December 1999 to January 2010, were retrospectively analyzed. Of the patients, the transplantation related mortality (TRM), relapse rate (RR), 5-year overall survival (OS) and disease free survival (DFS) were estimated by Kaplan-Meier analysis. The unfavorable prognostic factors were also statistically examined.@*RESULTS@#Hematopoietic reconstitution was achieved in 101 patients. At the last data of follow-up, the incidences of severe acute graft versus host disease (aGVHD) and extensive chronic GVHD were 15.38% and 25.53%, and the TRM and RR were 15.66% and 21.76%, respectively. The estimated 5-year OS and DFS for all patients were (73.49±4.59)% and (63.10±5.32)%, respectively. Those for acute myeloid leukemia (AML) patients were (63.00±9.51)% and (49.30±9.96)%, and those for chronic myeloid leukemia (CML) patients were (83.87±5.06)% and (74.55±6.79)%, respectively. The survival analysis suggested the poor prognostic factors for allo-HSCT recipients including female sex, severe aGVHD and refractory hematological malignancy. Further multivariate analyses revealed that severe aGVHD and refractory hematological malignancy were the independent risk factors of poor prognosis for the recipients (P<0.05). The 5-year DFS of severe aGVHD and refractory hematological malignancy patients was (48.22±12.69)% and (42.09±12.31)%, respectively. The TRM of severe aGVHD, HLA-mismatched graft and unrelated donor transplant was significantly higher than that of the corresponding control groups (57.14% vs. 4.81%, 33.33% vs. 10.41%, 26.09% vs. 9.28%; P<0.05). The RR of refractory hematological malignancy was significantly higher than that of the control group (41.09% vs. 15.63%, P<0.05).@*CONCLUSION@#The treatment of allo-HSCT can improve the disease free survival of patients with hematological malignany and is an important therapeutic method for hematological malignancy. Severe aGVHD and refractory hematological malignancy are the independent risk factors of poor prognosis for the allo-HSCT recipients with hematological malignancy.
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , China , Epidemiology , Graft vs Host Disease , Epidemiology , Hematologic Neoplasms , Therapeutics , Hematopoietic Stem Cell Transplantation , Methods , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Therapeutics , Leukemia, Myeloid, Acute , Therapeutics , Retrospective Studies , Transplantation, HomologousABSTRACT
purpose To investigate the release properties of gatifloxacin in situ pH-sensitive gel in vitro.Methods The improved paddle method and the membraneless model were applied in assessing the drug release behavior.Results The gel erosion and drug release were increased with the increase of surface area and shaking frequency.The cumulative quantities of gel erosion were well correlated with the cumulative release of drug loaded in the gel.Conclusion Gatifloxacin was released from in situ pH-sensitive gel with zero-order kinetics characters,and drug release was mainly controlled by gel erosion.
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Objective To evaluate the clinical outcome of autologous hemopoietic stem cell transplantation (AHSCT) for hematological malignancies. Methods Data of 61 patients with hematological malignancies who underwent AHSCT in Xiangya Hospital from April 1994 to August 2008 were retrospectively analyzed. There were 30 acute non-lymphoblastic leukemias (ANLL), 25 non-Hodgkin lymphoma (NHL), 3 Hodgkin lymphoma (HL), and 3 plasmacytoma. Mel 160 mg/m2 + Ara-C 2.0/2.5 g × 2 +Cy 1.8 g/m2 × 2, or TBI 8-10 Gy + Cy 1.8 g/m2 × 2 were mainly included in pretreatment regimens. Results All patients had rapid hemopoietic reconstitution. There was one patient who died of heart failure during the transplantation process. The rate of AHSCT related death was 1.6 %. The median follow up duration was 52(2-211) months. Forty-seven of 61 patients were still alive during the analysis. The probabilities of disease free survival (DFS) at 5 years were significantly different between these two groups: (77.5±5.5) % for AHSCT groups and (31.6±7.3) % for synchronous intensive chemotherapy groups(P <0.01). Conclusion AHSCT can be safely performed as an important treatment constituent for hematological malignancies.