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Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.
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Objective:To investigate the effects of hemophagocytic syndrome also known as hemophagocytic lymphohistiocytosis (HLH) on the clinical features and therapeutic efficacy of patients with Epstein-Barr virus-positive T-cell lymphoma (EBV-TCL).Methods:The clinical data of patients with EBV-TCL diagnosed by pathological examination in the First Affiliated Hospital of Guangzhou Medical University from November 2015 to August 2020 were retrospectively analyzed. According to whether they were accompanied with HLH at the time of onset, patients were divided into HLH group (10 cases) and non-HLH group (13 cases), and the clinical features and prognosis of the two groups were compared. The curative effects of different treatment methods and patients with different plasma EBV-DNA titers were compared.Results:Among 23 patients, 3 cases (13.0%) were in Ann Arbor stage Ⅰ-Ⅱ, 20 cases (87.0%) were in stage Ⅲ-Ⅳ; the International Prognostic Index (IPI) score was 1 point in 3 cases (13.0%), 2 points in 4 cases (17.4%), 3 points in 8 cases (34.8%), 4 points in 8 cases (34.8%). In the HLH group, there were 2 cases of aggressive NK-cell leukemia and 3 cases of childhood systemic EBV-TCL. There were no cases of above two pathological types in the non-HLH group. In the HLH group, the proportions of patients with fever, bone marrow invasion, IPI score > 2 points, and EBV-DNA > 10 4 copies/ml were higher than those in the non-HLH group (all P < 0.05). The objective response rate (complete remission plus partial remission) of all patients after chemotherapy was 47.8% (11/23); there were 3 cases undergoing hematopoietic stem cell transplantation in both the HLH group and the non-HLH group, and all achieved objective remission. The objective remission of 7 patients and 10 patients who did not undergo hematopoietic stem cell transplantation in the HLH group and non-HLH group after lymphoma chemotherapy had 0 case and 5 cases, respectively, and the difference was statistically significant ( P = 0.044). In the chemotherapy alone group, 5 of 17 patients had objective remission, 6 patients in the chemotherapy plus transplantation group had objective remission, and the difference was statistically significant ( P = 0.039). Among 16 patients whose plasma EBV-DNA titers turned negative, 11 patients had objective remission, and 7 patients whose plasma EBV-DNA titers were continuously positive had no objective remission, and the difference was statistically significant ( P = 0.001). The 1-year overall survival rate of all patients was 69.3%, and the 2-year overall survival rate was 52.0%. In the HLH group, the 1-year and 2-year overall survival rates of 7 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 42.9% and 66.7%, respectively. In the non-HLH group, the 1-year overall survival rates of 10 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 80.0% and 100.0%, respectively; the 2-year overall survival rates were 26.7% and 100.0%,respectively. The overall survival of patients receiving chemotherapy plus transplantation was better than that of those receiving chemotherapy alone in both the HLH group and the non-HLH group, and differences were statistically significant (all P < 0.05). Conclusions:The general clinical stage of patients with EBV-TCL is later, and the prognosis of EBV-TCL patients with HLH is worse. The therapeutic efficacy may be related to plasma EBV-DNA titers. Hematopoietic stem cell transplantation can improve the remission rate.
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Objective@#To investigate the clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response to pegylated interferon-α-2a (Peg-IFN-α-2a) therapy.@*Methods@#A total of 35 HBeAg-positive CHB patients with HBV DNA < 500 IU/ml who were treated with Peg-IFN-α-2a for 48 weeks and did not experience seroconversion of HBeAg were given telbivudine sequential therapy for 156 weeks. HBeAg clearance rate, HBeAg seroconversion rate, HBV DNA clearance rate, safety, and drug resistance rate were analyzed. The t-test was used for the analysis of continuous data and the chi-square test was used for the analysis of categorical data. A multivariate Cox regression analysis was used to identify the influencing factors for HBeAg seroconversion.@*Results@#Telbivudine sequential therapy achieved an ideal HBeAg seroconversion rate of 87.88% with good tolerability and low drug resistance. The HBeAg clearance rate and HBeAg seroconversion rate increased over the time of treatment and were 45.45% and 45.45%, respectively, at 24 weeks and 93.94% and 87.88%, respectively, at 156 weeks. No patient had virologic breakthrough or HBsAg clearance during treatment. The multivariate Cox regression analysis showed that baseline HBsAg level (hazard ratio [HR] = 0.404, P = 0.003) and > 0.5 lg IU/ml reduction in HBeAg at 24 weeks (HR = 2.196, P = 0.048) were predictive factors for HBeAg seroconversion at 156 weeks.@*Conclusions@#In HBeAg-positive CHB patients with suboptimal response to Peg-IFN-α-2a therapy, 156-week telbivudine sequential therapy has a good clinical effect and can be used as an optimal regimen for such patients.
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Objective@#To investigate the optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B (CHB) after suboptimal response to 24 weeks of pegylated interferon (Peg-IFN) α-2a.@*Methods@#A total of 188 patients with HBeAg-positive CHB who had suboptimal response to 24 weeks of Peg-IFN α-2a were randomly divided into entecavir group (n = 93) and telbivudine group (n = 95). The two groups received entecavir 0.5 mg/d and telbivudine 0.6 g/d, respectively, for 208 weeks. After 208 weeks of treatment, the following indices were assessed: HBeAg clearance rate and seroconversion rate, hepatitis B virus (HBV) DNA clearance rate (HBV DNA < 500 IU/ml), safety, and drug resistance rate. The data were subjected to intention-to-treat (ITT) analysis and per protocol (PP) analysis. Univariate and multivariate logistic regression analyses were performed for the drugs used and baseline characteristics in patients with or without HBeAg seroconversion, and stratification analysis was performed based on the baseline HBeAg level.@*Results@#Six cases in the entecavir group and four cases in the telbivudine group did not complete the treatment. Sequential entecavir and telbivudine were well tolerated and safe for all patients. There was a significant difference in HBV DNA clearance rate at 52 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 93.55% [87/93] vs 77.89% [74/95], χ 2 = 9.363, P = 0.002; PP analysis: 93.10% [81/87] vs 76.92% [70/91], χ 2 = 9.049, P = 0.003). The suppression rates of HBV DNA at 208 weeks of treatment were 95.70% (89/93) vs 92.63% (88/95) (ITT analysis) and 95.40% (83/87) vs 92.31% (84/91) (PP analysis). There was a significant difference in HBeAg seroconversion rate at 208 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 38.71% [36/93] vs 62.11% [59/95], χ 2 = 10.290, P = 0.001; PP analysis: 41.38% [36/87] vs 64.84% [59/91], χ 2 = 9.833, P = 0.002). Univariate and multivariate logistic regression analyses suggested that sequential use of telbivudine, male sex, and the baseline level of HBeAg were significantly associated with HBeAg seroconversion at 208 weeks of treatment (P = 0.003, hazard ratio [HR] = 0.386; P = 0.009, HR = 0.303; P = 0.001, HR = 3.502).@*Conclusion@#For patients with HBeAg-positive CHB after suboptimal response to 24 weeks of Peg-IFNα-2a, sequential use of telbivudine is the optimal treatment regimen according to the baseline level of HBeAg (baseline guidance). The incidence of HBeAg seroconversion during 208 weeks of sequential treatment can be significantly increased according to the HBeAg decline curve in early treatment (24 weeks) and 104 weeks (response guidance).
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Objective: To explore the effect of salvianolate combined with the conventional therapy on acute ischemic stroke and observe the influence on serum inflammatory cytokines of interleukin-6(IL-6).Methods: According to the random number table, 70 patients were randomly divided into the observation group (n =35) and the control group (n =35), and both were given the conventional therapy for acute ischemic stroke.The observation group was given intravenous injection of 200mg salvianolate in 250ml normal saline once a day additionally.The treatment course was 2 weeks.Another 30 persons with physical examination were in the healthy control group.The neurologic damage deficiency score (NIHSS score) was evaluated after the 3-, 7-,10-and 14-day treatment in the groups, the serum IL-6 in 24 h after onset, and after the 3-, 7-,10-and 14-day treatment was detected and compared with that in the healthy control group.Results: After the 7-day treatment, NIHSS score in the observation group decreased significantly when compared with that on admission (P＜0.05), and remained the decreasing trend.After the 10-day treatment, NIHSS score in the control group decreased significantly when compared with that on admission (P＜0.05).After the 7-day treatment, NIHSS score in the observation group was lower than that in the control group (P＜0.05).Compared with that in the healthy control group, the serum level of IL-6 in the observation group and the control group was higher in 24 h of admission (P＜0.05).The serum level of IL-6 in the observation group decreased after the 7-day treatment, and was similar to that in the healthy control group after the 14-day treatment (P＞0.05).The serum level of IL-6 in the control group decreased after the 10-day treatment, while was higher than that in the healthy control group during the whole study period (P＜0.05).The serum level of IL-6 in the observation group was lower than that in the control group after the 7-day treatment (P＜0.05), and the peak value in the observation group was notably lower than that in the control group (P＜0.05).Conclusion: Salvianolate combined with the conventional therapy can effectively decrease the NIHSS score and the content of IL-6 in the patients with acute ischemic stroke, which shows better effect than the conventional therapy alone.
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Objective To observe the influence of acupuncture treatment on parturition process.Methods 545 pregnant women delivered in our hospital were selected,excluding those with cesarean section indication.On voluntary principle and randomized principle,primipara aged from 22 to 30 who agreed with natural labor were divided into two groups:observation group and control group.Pregnant women in observation group were received acupuncture treatment during latent phase.The following indexes of the two groups were recorded and compared:labor time of the first stage and the second stage,the case for inertia of uterus,cesarean sections,postpartum hemorrhage amount and Apgar score of new-born.Results The labor time of the first stage and the second stage of the control group were (178.55 ± 56.87) min and (130.70 ± 77.22) min,and which of the observation group were (53.87 ±22.33) min and (33.25 ± 15.55) min,there was significant differenec between the two groups(t =3.97,4.11,all P ＜0.05).The differences in the pilot failed to cesarean section rate(14.2％ and 13.6％),postpartum hemorrhage and the perinatal outcome were not significant between the two groups.Conclusion Acupuncture and moxibustion can accelerate labor.
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Notch signaling can control T cell development and differentiation and lead to acute T cell lymphoma/leukemia (T-ALL). Most Notch1mutations in human T-ALL are the HD domain and the PEST domain. Aberrant Notch1activation can induce T-ALL by PI3K/Akt, mTOR or/and NF-κB pathways. Some recent reports suggested that Notch signaling could not only control T cell development,but also has a role in acute myeloid leukemia (AML) and Graft-versus-host Disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Moreover,Notch signaling can regulate the expansion of HSC as well as generate increased numbers of progenitor cells which are capable of rapid repopulation to improve HSC homeostasis and hematopoietic recovery after allo-HSCT.
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Objective To investigate the distribution of TCR Vβ genealogy and clonal expansion in peripheral blood after infusing mesenchymal stem cells (MSC) in patients with chronic GVHD. Methods The complementarity determining region 3 (CDR3) of 24 TCR Vβ subfamily genes in peripheral blood mononuclear cell from 1 case with cGVHD after allogeneic hematopoietic stem cell transplantation (Allo-HSCT),who were treated with infusing MSC,were amplified using RT-PCR. The blood samples were taken at the first and the fifth day after 1st infusion; and the first day,the 10 th day and the 20 th day after the second infusion of MSC,as well as the MSC infused as control . The products were labelled by fluorescein and then analyzed the CDR3 size with gene scan technique to determine the clonality of T cells. Results There were no expression of TCR Vβ subfamily with the MSC infused and after the 1st day of the first infusion of MSC. Then 3,10,14,10 Vβ subfamilies clones are appeared at the other time points,of which were polyclone and oligoclone predominately. In the same time,the manifestations of cCVHD have been abated. Conclusion MSC played a certain role in reviving the immune function of the patients after Allo-HSCT and mitigating the disease of chronic GVHD. Lineage analysis of TCR Vβ subfamily showed some predominant expression.
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Objective To explore the possible effects of methyl methanesulfonate sensitive 2(MMS2)in the process of angiotensin Ⅱ inducing differentiation of neural stem cells (NSCs) into dopaminegic phenotype neurons. Methods NSCs were isolated from the brain of newborn rats and were cultured in the serum-free medium.Identification of neural precursor cells was done by Nestin immunocyt ochemical staining. Then the second generation of NSCs was divided into the following six groups: A, control; B, AⅡ; C, AT1 antagonist ZD7155; D, ZD7155+AⅡ; E, AT2 antagonist PD123319; F, PD123319+AⅡ. The detection of expression of MMS2 and TH mRNA level was done by real-time PCR. The silence of the expression of MMS2 in NSCs was brought about via the transfection of MMS2-siRNA, and then the NSCs were induced to differentiate into dopaminegic neurons. The expression of TH mRNA level in the cells of the groups after transfection was detected by real-time PCR. Results Nestin-positive cells were observed in suspended growth in the medium.Real-Time PCR revealed that the MMS2 and TH mRNA expression of group B and D were significantly higher than that of the control group(P<0.05), There was no significant difference in MMS2 and TH mRNA expression between group C, E, F and the control, respectively. Conclusion AⅡ increased the expression of MMS2 mRNA in NSCs and induced the differentiation of NSCs into DA neurons via AT2 recepter. MMS2 may play important roles in the process of angiotensin Ⅱ inducing NSCs to differentiate into dopaminergic neurons.
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Objective To investigate the impact of auto and allogenic mesenchymal stem cells (MSC) transplantation on hematopoietic reconstitution. Methods MSC from auto, donor bone marrow or embryonic tissue were cultured and expanded in vitro in the serum culture system. Five patients received hematopoietic stem cell transplantation (HSCT) were investigated. Case 1 of systemic lupus erythematosus and Case 2 of non-hodgkin' s lymphoma (NHL) received auto MSC transplant before auto-HSCT. Case 3 of paroxysmal nocturnal hemoglobinuria received HLA-identical allogenic MSC transplant before HLA-identical allo-HSCT.Case 4 of chronic myelocytic leukemia and Case 5 of NHL had delayed hematopoietic reconstitution (129th and 78th day, respectively) after allo- and auto-HSCT, respectively, and received MSC from embryonic tissue.Results Case 1, 2 and 3 had no manifested side effects after MSC transplantation combined with HSCT.Neutrophil count of case 1, 2, and 3 were over 0.5 ×109/L at 1st, 10th and 10th day, respectively, platelet count were over 20 ×109/L at 1st, 8th and 33th day, respectively, and agranulocytosis at Ost, 7th and 12th day, respectively. The treatment of embryonic tissue MSC transplant was confirmed to fail for Case 4 and 5.Conclusion The time of MSC transplant has a great impact on hematopoietic reconstitution. MSC transplantation and HSCT performed simultaneously can improve hematopoietic reconstitution. However, the impact of MSC on patients with delayed hematopoietic reconstitution after HSCT needs further study.
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Objective To investigate the morbidity,clinical manifestations,and imageology characteristics,and the influencing factors of severe cyclosporine A(CsA)-related neurotoxicity(SNCT)in the patients after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Finding of SNCT was carried out in 164 allo-HSCT recipients from January 2003 to June 2006.Clinical characteristics were analysed,including precursory symptoms and clinical manifestations.Associations between the onset of SNCT with blood CsA levels,age,transplant types,human leucocyte antigen(HIJA)matching,conditioning regimens,antihuman thymocyte globulin(ATG)used in the prevention and treatment for graft-versus-host disease(GVHD)and intravenous corticosteroid used for acute GVHD were analyzed.Statistical analysis was performed with Binary Logistic Regression using SPSS/PC version 11.0.Results Thirteen patients(7.93%)were identified to have SNCT,including seizures(n=8,4.88%),paralysis(n=6,3.66%),coma(n:2,1.22%),cerebllar ataxia(n=3,1.83%)and chondrioid encephalomyopathy (n=1,0.61%).All the patients had precursory symptoms prior SNCT including headache(n=8),agitation(n=4)and hypertension(n=6).Magnetic resonance imaging(MRI)performed in twelve patients after SNCT showed that eleven patients had signal abnormalities in cerebral cortex and cerebral white matter.Six patients examined with computerized tomography(CT)had no abnormal findings.After extenuation or withdrawal of CsA.ten patients had complete recovery.two had partial recovery and one died of SNCT.Simple effect analysis of Binary Logistic Regression showed that the associations between the onset of SNCT with blood CsA levels.transplanta types.HLA matching.ATG used in the prevention and treatment for GVHD and intravenous corticosteroid used for acute GVHD were of statistical significance.The multiple effect analysis of Binary Logistic Regression showed that the associations of the onset of SNCT with blood CsA levels and ATG used had statistical significance and the odds ratio(OR)was 1.007(P=0.006) and 6.727(P=0.030),respectively.Conclusions 91.67%of the allo-HSCT recipients with SNCT have MRI abnormalities.High blood CsA levels and the use of ATG Call elevate the risk of the occurrence of SNCT.
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Objective To explore the relapse,therapeutic effect,risk and prognostic factors of the pulmonary invasive fungal disease(IFD)in patients with a history of pulmonary IFD following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Fourteen patients with a history of pulmonary IFD received allo-HSCT between March 2005 and October 2006.Before transplantation,10 patients obtained complete remission(CR)and 4 partial remission(PR)after antifungal therapy.Antifungal prophylaxis was initiated on the first day of the conditioning therapy.Logistic regression models were used for multivariable analyses.Results The relapse rate of pulmonary IFD after allo-HSCT was 71.43%(10/14).Of 10 patients in CR,6 relapsed and all four patients in PR relapsed.Seven patients relapsed less than 3 months and 3 relapsed between four and six months after transplantation.Among the 10 patients with a history of IFD who relapsed after transplantation,9 patients received antifungal therapy,4 obtained CR,2 PR again and the other 3 didn't obtain remission.The effective rate of anti-fungal therapy was 66.67% and the pulmonary IFD-related mortality was 35.71%(5/14).There was no significant difference between amphotericin B,itraconazde and voriconazole for antifungal prophylaxis in patients with a history of pulmonary IFD(P=0.122).No risk and prognostic factors of the pulmonary IFD was identified by multivariable analyses.Conclusion Pulmonary was not an absolute contraindication for allo-HSCT,and patients with a history of pulmonary IFD had a higher relapse rate and transplant-related mortality after receiving allo-HSCT.