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Objective:To investigate the effect of paeoniflorin on toll-like receptor 4(TLR4)/nuclear transcription factor(NF-κB) signaling pathway of streptozotocin combined with ovariectomized mice, and to explore whether it can improve the cognitive impairment of ovariectomized diabetic mice.Methods:Ninety female C57BL/6J mice were divided into SHAM group, ovariectomy group, diabetes group(intraperitoneal injection of STZ 50 mg·kg -1·d -1 for 5 consecutive days), dual model group(DM modeling and OVX operation), paeoniflorin low-dose intervention group(OVX+ STZ+ L-PF 50 mg·kg -1·d -1), paeoniflorin high-dose intervention group(OVX+ STZ+ H-PF 100 mg·kg -1·d -1; all groups n=15). After 8 weeks of paeoniflorin intervention, their cognitive function was tested by behavioral experiments(Morris water maze and Y maze). The pathological changes of hippocampal tissue were observed by HE and Nissl staining. The mRNA expressions of TLR4, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) in hippocampal tissues were detected by real-time fluorescence quantitative PCR. The expression of TLR4, NF-κB P65, TNF-α, IL-6, IL-1β, β-amyloid protein(Aβ), tau proteins, and p-tau proteins were detected by Western blot. Results:Compared with SHAM group, the learning and memory ability of ovariectomy group, diabetes group and dual model group decreased, hippocampal cells were damaged, and the expression of related gene mRNA and protein were increased, especially in dual model group; Compared with dual model group, paeoniflorin intervention could delayed the learning and memory impairment, improve cognitive function, reduce the degree of hippocampal injury, and decrease the expression levels of related gene mRNA and protein, The above changes were the most pronounced at paeoniflorin high-dose intervention group.Conclusion:Paeoniflorin improves cognitive dysfunction in ovariectomized diabetic mice by inhibiting TLR4/NF-κB signaling pathway.
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BACKGROUND@#Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients.@*METHODS@#Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes.@*RESULTS@#Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality.@*CONCLUSION@#Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients.@*CLINICAL TRIAL REGISTRATION@#Chinese Clinical Trail Registry, No. ChiCTR2100044625.
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Humanos , Pressão Sanguínea , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos de Coortes , Respiração Artificial , Pacientes Internados , Mortalidade HospitalarRESUMO
Objective:To investigate the changes of various cytokines and coagulation function in B cell acute lymphoblastic leukemia(ALL) patients with different CRS scores during CD19-CAR-T cell immunotherapy.Methods:87 patients with B-ALL hospitalized in the First Affiliated Hospital of Soochow University and 30 normal controls were enrolled into this study from July 2018 to October 2020. The age of the patients was 32(20, 56) years old and 36(41.4%) were female. All these coagulation indicators, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, fibrinogen (Fg) were analyzed by automatic blood coagulation in B-ALL patients before and after treated with CAR-T cell. The ratio of CD19-CAR-T cells and the expression of IL-6, IL-10, IFN-γ, TFN-α, IL-2, IL-4, and IL-17A were analyzed using flow cytometry. The patients′ clinical parameters were detected, and the CRS classification of severity was made according to the standard of consensus.Results:Patients with CRS>3 had prolonged PT and APTT, increased D-dimer, and decreased fibrinogen ( P<0.05). The levels of cytokines of IFN-γ, IL-6, and IL-10 were significantly higher in patients with CRS>3 than that in controls ( P<0.05).The D-dimer level is positively correlated with IL-10. Conclusion:Patients with severe CRS grading have significant coagulation dysfunction in CD19-CAR-T cell immunotherapy. Cytokines IFN-γ, IL-6, and IL-10 may affect coagulation function and CRS grading during CD19-CAR-T cell immunotherapy.
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Objective:To explore the application of venetoclax in transplantation of patients with refractory acute myeloid leukemia (AML).Methods:The diagnosis and treatment process of a patient with refractory AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) under venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen after induction therapy failure in the First Affiliated Hospital of Soochow University in March 2020 were retrospectively analyzed.Results:The patient was a 28-year-old female who was diagnosed with refractory AML. The patient was initially given induction chemotherapy with IA (idarubicin+cytarabine) (3+7) regimen, but the disease did not relieve, then the induction chemotherapy with CLAG (cladribine+cytarabine+granulocyte colony stimulating factor) regimen was given, but the disease still did not relieve. After chemotherapy with venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen, salvage haploid allo-HSCT was performed. Re-examination of bone marrow showed remission, and implantation was successful. The patient was followed up for 100 days and had sustained remission, and no transplantation complications occurred.Conclusion:For refractory AML patients who have failed primary induction therapy, the use of venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen can be used as a preferred solution for salvage allo-HSCT.
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Objective: To establish the glioma-bearing nude mouse models, and to investigate the effect of HOXA4 on the growth of glioma U251 cells in vivo and its regulatory effect on the Wnt/β-catenin sgnal pathway and its mechanism Methods: The glioma U251 cell line stably transfected with HOXA4 siRNA (si-HOXA4) and the U251 cell line stably transfected with blank vector (si-NC) were established by lentivirus transfection The U251, si-NC, and si-HOXA4 cells were respectively inoculated under the skin of the neck and back of the BALB/c nude mice to establish the glioma-bearing nude mouse models named as control group, si-NC group, and si-HOXA4 group. The tumorigenesis of nude mice in various groups were observed and the tumor growth curve was drawn. The tumor tssue was stripped after the mice were sacrificed on the 21 th day, and the volume and wght of tumor were measured; the relative mRNA expresson amounts of HOXA4, CTNNB1, and Gsk3fS in tumor tssue of the nude mice in various groups were detected by qRT-PCR method; the expresson levels of HOXA4, β-catenin, Gsk3β, CyclinD1, and P53 proteins in tumor tissue of the nude mice in various groups were detected by immunohistochemstry (IHC) method. Results: Compared with si-NC group and control group, the volume and wght of tumor of the nude mice in si-HOXA4 group were gnificantly decreased (P<0. 05). The relative expresson amount of HOXA4 mRNA and the expresson level of HOXA4 protein in si-HOXA4 group were gnificantly lower than those in the other groups (P<0. 05). Compared with si-NC group and control group, the relative expresson amount of CTNNB1 mRNA and the expresson levels of β-catenin and CyclinDl proteins in si-HOXA4 group were significantly decreased (P<0. 05), and the expresson levels of Gsk3β and P53 proteins were gnificantly increased (P<0. 05). Conclusion: Inhibition of HOXA4 expresson in human glioma U251 cells can regulate the expressons of CyclinDl and P53 through Wnt/-catenin gnal pathway in vivo, thus inhibiting the tumor growth of glioma-bearing nude mice.
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Objective@#To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR1).@*Methods@#A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases).@*Results@#Of 107 patients (59 males and 48 females) , with a median age of 33 (16-59) years old and a median follow-up of 36.5 (5.3-79.1) months, the overall relapse rate was 20.6% (22/107) , and overall mortality rate was 18.7% (20/107). The 5 years cumulative relapse rate (CIR) of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 39.7%, 6.2%, 14.3% and 5.6%, respectively (P<0.001). The CIR of the observed group was lower than the HD-Ara-C group. The 5 years progression-free survival (PFS) rate of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 44.7%, 93.8%, 85.7% and 78.1%, respectively (P=0.011). The PFS of observed groups were similar, but superior to that in HD-Ara-C group. The 5-year overall survival (OS) in four groups was 54.9%, 100%, 92.9% and 77.4%, respectively (P>0.05). Multiple factors analysis showed that compared to HD-Ara-C regimen, allo-HSCT could improve PFS (HR=0.376, P=0.031) , but not OS (P>0.05) ; micro-transplantation and auto-PBSCT could not improve the PFS or OS (P>0.05).@*Conclusion@#As compared with HD-Ara-C regimen, allo-HSCT could obviously decrease CIR, improve PFS, but treatment-related mortality is high. These results show that auto-PBSCT and micro-transplantation have similar outcomes, compared to HD-Ara-C regimen, so both can be used as a option of consolidation treatment for favorable-risk AML.
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BACKGROUND: With the optimization of transplantation scheme and the emergence of graft-versus-host disease (GVHD) therapy drugs, allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recent years has made great progress that makes patients with hematological malignancies have more long-term survival opportunities. OBJECTIVE: To compare the efficiency and safety of three types of allo-HSCT used in the treatment of adults with Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (Ph+ALL).METHODS: A total of 69 patients with Ph+ALL who received allo-HSCT from June 2006 to November 2013 were enrolled, including 23 cases of sib-matched donor transplantation, 24 cases of unrelated-matched donor transplantation, and 22 cases of haploidentical donor transplantation. There were 54 cases of CR1, 13 cases of CR2 to CR3 and 3 cases of relapse. The bone marrow or/and peripheral blood stem cells were used for transplantation. All patients were subjected to pretreatment consisting of cytarabine, busulfan, cyclophosphamide and total body irradiation. GVHD was prevented by combined use of immunosuppressants including cyclosporine A, short-term methotrexate, mycophenolate mofetil and anti-human thymocyte globulin, etc.RESULTS AND CONCLUSION: The results showed that 68 patients acquired hematopoietic reconstitution, and only 1 case of haploidentical donor transplantation failed. The mean follow-up period was 20.4 months. The acute GVHD incidence of the sibling matched-HSCT, unrelated donor HSCT and related haploidentical allo-HSCT was 30％, 33％ and 45％,respectively; the chronic GVHD incidence (cGVHD) incidence was 22％, 29％ and 36％, respectively; the incidence of aGVHD and cGVHD between groups showed no statistically significant difference. Transplant related mortality (TRM) was 9％, 29％ and 41％, respectively, and there was a significant difference among groups (0.01 < P < 0.05). Recurrence rates were 17％, 21％ and 14％, respectively, and there was no significant difference among groups. The 3-year overall survival rates were 68％, 49％ and 43％, respectively; there were significant differences between sib-matched-HSCT and the other two groups, but no statistically significant difference was found between unrelated donor HSCT and related haploidentical allo-HSCT groups. The 3-year overall survival rate was 58％ for 54 patients in CR1 and 41％ for 15 patients in non-CR1 states. To conclude, the sib-matched HSCT has better effect than unrelated donor transplantation and related haploidentical allo-HSCT; Ph+ALL patients should do transplantation as early as possible in the state of CR1.
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Objective To explore the relationship and the clinical significance of homeobox gene B1 (HOXB1 )and microRNA-31 75 (miR-31 75)expressions in human glioma.Methods The expression levels of HOXB1 and miR-31 75 in 60 glioma tissues and 1 5 normal brain tissues were analyzed by real-time fluores-cent quantitative PCR (qRT-PCR).Spearman rank correlation analysis was performed to explore the relation-ship between HOXB1 and miR-31 75 in human glioma tissues.The relationship between HOXB1 (or miR-31 75)and clinical pathological characteristics of glioma patients was analyzed.The correlation of HOXB1 (or miR-31 75)and survival rate was calculated by Kaplan-Meier.And COX regression models were used to assess the prognostic factors.Results Compared with normal brain tissues,the expression of HOXB1 was significant-ly decreased in glioma tissues (1 .498 ±0.323 vs.0.946 ±0.588,t =-5.680,P =0.000);and the expre-ssion of miR-31 75 was obviously increased in glioma tissues (1 .008 ±0.355 vs.2.076 ±0.841 ,t =4.274, P =0.000),and HOXB1 expression was negatively correlated with miR-31 75 expression in glioma tissues (r =-0.601 ,P =0.000).HOXB1 expression was related with histologic grade (χ2 =4.848,P =0.028), and miR-31 75 expression was related with histologic grade (χ2 =5.640,P =0.01 8)and Karnofsky score (χ2 =4.785,P =0.029).The results of Kaplan-Meier revealed that there were significant differences in median survival time between HOXB1 (or miR-31 75)high-expression group and HOXB1 (or miR-31 75)low-expression group [HOXB1 :(21 .0 ±4.0)months vs.(7.0 ±0.8)months;χ2 =7.495,P =0.006;miR-31 75:(6.0 ±0.6)months vs.(1 6.0 ±5.8)months;χ2 =9.591 ,P =0.002].COX regression models showed that tumor degree (RR =6.556,95% CI:1 .1 96-35.952,P =0.002),HOXB1 (RR =0.01 8, 95%CI:0.001 -0.31 2,P =0.006)and miR-31 75 (RR =2.098,95%CI:1 .663-7.51 3,P =0.037)were independent prognostic factors for prognosis.Conclusion The HOXB1 expression may be negatively correlated with miR-31 75 in human glioma tissues,and the expression levels of HOXB1 and miR-31 75 are associated with the glioma malignant degree,survival time and prognosis of glioma patients.
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Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 yeas of age. Methods From May 2002 to January 2010, 35 patients (＞ 50 years) with malignant hematological diseases received allogeneic hematopoietic cell transplantation. In 35 patients, 18 patients were conditioned with non-myeloablative regimen and 17 patients with myeloablative regimen. The outcome,engraftment and prognosis of allogeneic hematopoietic cell transplantation were analyzed. Results The hematopoetic reconstitution was achieved in 32 of 35 patients. The median time of granulocyte count exceeding 0. 5 × 109/L was 12 days and the that of platelet count exceeding 20 × 109/L was 17days. The cumulative incidence of aGVHD was 48. 6 %, and 37. 9 % patients developed cGVHD.The estimate probability of cumulative survival at 5 years was 48. 5 %, The estimate probability of cumulative mortality rate was 51.5 %, and the estimated transplant-related mortality was 22. 9 %.The relapse rate was 11.4 %. There was significant difference except for the incidence of cGVHD.Conclusion Allogeneic hematopoietic cell transplantation may be appropriate for older patients with malignant hematological diseases.
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OBJECTIVE To study the clinical feature of nosocomial infection and analyze the correlative reasons,to offer the scientific theory basis for preventing and controlling the nosocomial infection. METHODS A retrospective survey was undertaken in the data of hospitalized cases during 2007. RESULTS Totally 2325 nosocomial infections in 54 505 patients were analyzed in 2007.The infection rate of nosocomial infection was 4.27%;the highest infection rate was in ICU(33.57%);the infection sites were different in distinct departments and the most common infection site was lower respiratory tract(27.19%);among pathogens isolated from nosocomial infection cases,48.05% of them were Gram-negatives,23.25% were virus,14.45% were fungi,and 14.15% were Gram-positives;the infection rate was diverse in different months. CONCLUSIONS Nosocomial infection rate is related to different underlying diseases;there are many effective actions to reduce the nosocomial infection,such as strengthening the nosocomial infection management,using the antibacterial drugs reasonably and preventing communicable diseases prevalence.
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Objective To observe the effect of pentoxifylline(PTX),albendazole(ABZ),and a combination of PTX and ABZ in mice infected with Echinococcus multilocularis(E.M).Methods The first part of the experiment was to observe the in vitro effect of PTX on the cultured E.M protoscolex.In the second part,mice were infected by abdominal inoculation of E.M and divided into groups given by ABZ 50 mg/kg?d,PTX 360 mg/kg?d,PTX 180mg/kg?d,and a combined regimen ABZ 50 mg/(kg?d)+PTX 180 mg/(kg?d).Another infected group and a uninfected group served as controls which received normal saline only.100 days post-treatment,the mice were sacrificed for further observation.Indicators included wet weight of the cyst,cyst inhibition rate,level of serum cytokines TGF-? determined by ELISA,IL-2 and IL-10 determined by radio-immunoassay(RIA).Results The inhibition rate on cysts of the combined ABZ and PTX was 88%,considerably higher than 58 % of the group ABZ.The serum TGF-? and IL-10 decreased and IL-2 increased after treatment in comparison to the controls.Conclusion The PTX and ABZ combination shows better effect on E.multilocularis infection than that of single ABZ.PTX might help increase immunity of the mice.