ABSTRACT
Objective To investigate the effects of ginkgo biloba extracts ( EGb761) on learning and memory and the protective effect on hippocampal neurons in rats with vascular dementia (VD). Meth-ods Ninety rats were randomly divided into sham-operated group,model group and EGb761-treated group, with 30 rats in each group. Rats in each group were examined at 15 days,1 month and 2 months,with 10 rats in each time point. VD model was established by bilateral carotid artery occlusion combinding with injection of sodium nitroprusside. Morris water maze test was used to detect the learning and memory function of rats. The expression of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence. Western-blot was used to detect the protein expression of P-glycoprotein ( P-GP ), excitatory amino acid transporters 2 ( EAAT2),caspase-3 and cleaved caspase-3. RT-PCR was used to detect the mRNA expression of P-GP and EAAT2 in the hippocampus of rats in each group. Results Compared with sham-operated group,the escape latency (EL) was significantly prolonged at each time point in model group ( sham-operated group:15 days (15. 52±3. 23) s,1 month ( 14. 21 ± 2. 62) s,2 months ( 15. 37 ± 1. 66) s;model group:15 days ( 30. 35 ± 2. 30)s,1 month(40. 78± 3. 55) s, 2 months( 33. 88± 1. 47) s; all P<0. 01). The EL of EGb761-treated group was significantly shorter than that of the model group(EGb761-treated group:15 days(25. 69±2. 44)s, 1 month(20. 78±1. 72)s,2 months(18. 23±1. 67)s,all P<0. 01). Immunofluorescence showed that the ex-pression of GFAP in EGb761-treated group was lower than that of the model group (P<0. 01). Western blot showed that cleaved caspase-3 protein expression in EGb761-treated group at each time point was significant-ly lower than that in the model group (P<0. 01). Western-blot and RT-PCR results showed that the protein and mRNA expression of P-GP and EAAT2 in EGb761-treated group at 15 day and 1 month time points were significant increased than those in the model group (P<0. 01). At 2 month time point,which were lower than those in the model group (P<0. 01). Conclusion EGb761 can improve the learning and memory ability of VD rats,and regulate the protein and mRNA expression of P-GP and EAAT2 in hippocampus of VD rats at different time points (up-regulated in 1 month and down-regulated in 2 month),and down-regulate the ex-pression of cleaved caspase-3 and GFAP at different time points,thereby delaying the brain damage of VD rats and protecting neurons.
ABSTRACT
The support treatment of low-risk myelodysplastic syndromes (MDS) patients whose revised international prognostic score system (IPSS-R) is defined as 3.5 points remains the main treatment. The erythropoiesis stimulating agent (ESA) is the best choice for patients with del (5q) MDS as long as the endogenous erythropoietin (EPO) level is less than 500 U/L (preferably<200 U/L). The application of EPO for patients with treatment failure or relapsed after transfusion, chooses are immunosuppressant, transforming growth factor beta inhibitors and lenalidomide. Del (5q) syndrome could benefit from lenalidomide, and some patients after discontinuation of treatment still have been stable in peripheral blood. Thrombocytopenia caused serious hemorrhage rarely; thrombopoietin receptor analogs could reduce bleeding and improve the platelet count. These drugs can be used in patients with bone marrow blast counts of < 0.05. If treatment failed or advanced to high-risk MDS or transformed to acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation might be required. Combined with reports in the 59th American Society of Hematology (ASH) Annual Meeting, this article describes the treatment strategies for low-risk MDS.
ABSTRACT
Myelodysplastic syndromes (MDS) is a clinical heterogeneous disease characterized by impaired hematopoietic function and morphologic abnormalities of the bone marrow. Genomic studies show that MDS is usually driven by a series of multistep somatic cell genetic processes that affect the core genome. By definition, reproducible MDS drives mutations leading to cloning advantage. In addition, exposure factors, such as cytotoxic chemotherapy or genetic propensity of the reproductive system, could affect the pathogenesis and clinical outcomes of the disease. Combined with the reports in the 59th American Society of Hematology (ASH) Annual Meeting, the article introduces the genetic characteristics of MDS, in order to improve the diagnosis of MDS and the understanding of the pathogenesis of treatment-related MDS as well as the genetic tendency of MDS in the reproductive system.
ABSTRACT
OBJECTIVE:To investigate clinical efficacy and safety of Miao medicine Jinyin huashi granules combined with western medicine in the treatment of chronic calculous cholecystitis(CCC). METHODS:A total of 120 CCC patients in our hospi-tal during Jan. 2014-Jan. 2016 were randomly divided into control group and observation group,with 60 cases in each group. Con-trol group was given 50％ Magnesium sulfate solution 10 mL orally before meal,tid;amoxicillin 0.5 g orally,tid+Racanisodamine tablets 10 mg,tid+Compound dantong tablets 1 slice,tid,after meal. Observation group was additionally treated with Miao medi-cine Jinyin huashi granules 15 g,tid,on the basis of control group. Both groups were treated for consecutive 4 weeks. Clinical effi-cacies,the improvement of upper abdominal pain,nausea and greasy,calculus were observed in 2 groups. The thickness of gall-bladder,serum levels of IL-2 and IL-5,mRNA and protein expression of CYP7A1 and B-UCT were compared between 2 groups before and after treatment. The occurrence of ADR was recorded in 2 groups. RESULTS:Total response rate of observation group was 96.67％,which was significantly higher than 88.33％ of control group,with statistical significance (P<0.05). One d and one week after treatment,the improvement rates of upper abdominal pain were 63.33％ and 81.67％ in observation group, which were significantly than 36.67％ and 50.00％ of control group,with statistical significance(P<0.05). There was no statisti-cal significance in the improvement rate of nausea or greasy after treatment between 2 groups(P>0.05). The stone-free rate of ob-servation group was 33.33％ and significantly higher than 11.67％ of control group,with statistical significance(P<0.05). Before treatment,there was no statistical significance in the thickness of gallbladder wall,serum levels of IL-2 or IL-15,mRNA and pro-tein expression of CYP7A1 or B-UCT between 2 groups(P>0.05). After treatment,the thickness of gallbladder wall,serum lev-els of IL-2 and IL-15 were all decreased significantly in 2 groups,while mRNA and protein expression of CYP7A1 and B-UCT were increased significantly;observation group was significantly better than control group,with statistical significance (P<0.05). There was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Miao medicine Jinyin huashi granules combined with western medicine show significant therapeutic efficacy for CCC,can effectively improve right upper quadrant pain,nausea and greasy,decrease serum levels of IL-2 and IL-5 and up-regulate mRNA and protein expression of CYP7A1 and B-UCT with good safety.
ABSTRACT
The treatment of patients with myelodysplastic syndromes (MDS) has included primarily supportive care (blood transfusions, colony stimulating agents, iron chelation, etc.) and new drugs, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For those who are no longer benefiting from these agents, there is nearly nothing to do with effective therapies. When those drugs are ineffective, what the doctors could do is optimizing the delivery of hypomethylating agents (HMT) by dosing appropriately, sequencing appropriately, and using thoughtful combinations; as well as improving drug formulations (oral formulations and/or novel formulations) and working toward better selection of patients for best upfront mutation-directed therapy. Hopefully, the drug targeting and patient selection for optimal HMT treatment of MDS will be improved. Furthermore, ongoing research is focused on identifying unique agents to rescue MDS patients who have progressed despite HMT. Agents such as rigosertib are now focused on its application in specific MDS populations who might most likely benefit from this therapeutic approach [primary refractory and high-risk international prognostic scoring system (IPSS) patients]. Doctors eagerly await results of single-agent programmed death 1 (PD-1) and its inhibitors, or combination with HMT to the upfront and relapsed MDS setting. For the minority of patients who have specific targetable mutations, the selective agents (IDH1/2) are highly promising. Bone marrow transplantation remains the only offer for cure, but is depressingly unrealistic given the majority of the elderly and frail patients at the time of MDS progression.
ABSTRACT
New progress of treatment of low-risk myelodysplastic syndromes (MDS) reported in the 58th American Socienty of Hematology (ASH) Annual Meetings was reviewed. Anemia is a single common symptom of low-risk MDS, and erythropoietic-stimulating agents (ESA) may be effective. The dose and duration of erythropoietic-stimulating agents (ESA) are critical to determine efficacy. If the treatment of ESA failed, the available options may include lenalidomide (approved for del5q positive cases), hypomethylating agents and a rather large number of experimental agents. The choice for the second-line treatment must consider the biologic, cytogenetic and molecular-identified characteristics of individual patient, as well as frailty and comorbidities. Other cytopenias rarely appear alone. Thrombomimetic agents for thrombocytopenia has been proposed in clinical trials, but there were some safety issues. Although neutropenia is targeted symptomatically with growth factor supportive care, the immunosuppressive therapy is indicated mainly for pancytopenic and hypoplastic low-risk MDS. Finally, hematopoietic stem cell transplantion is the curative option also for low-risk MDS, but it should be carefully evaluated to balancing toxicity and the possibility of survival advantage.
ABSTRACT
The treatment of patients with myelodysplastic syndromes (MDS) has included primarily supportive care (blood transfusions, colony stimulating agents, iron chelation, etc.) and new drugs, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For those who are no longer benefiting from these agents, there is nearly nothing to do with effective therapies. When those drugs are ineffective, what the doctors could do is optimizing the delivery of hypomethylating agents (HMT) by dosing appropriately, sequencing appropriately, and using thoughtful combinations; as well as improving drug formulations (oral formulations and/or novel formulations) and working toward better selection of patients for best upfront mutation-directed therapy. Hopefully, the drug targeting and patient selection for optimal HMT treatment of MDS will be improved. Furthermore, ongoing research is focused on identifying unique agents to rescue MDS patients who have progressed despite HMT. Agents such as rigosertib are now focused on its application in specific MDS populations who might most likely benefit from this therapeutic approach [primary refractory and high-risk international prognostic scoring system (IPSS) patients]. Doctors eagerly await results of single-agent programmed death 1 (PD-1) and its inhibitors, or combination with HMT to the upfront and relapsed MDS setting. For the minority of patients who have specific targetable mutations, the selective agents (IDH1/2) are highly promising. Bone marrow transplantation remains the only offer for cure, but is depressingly unrealistic given the majority of the elderly and frail patients at the time of MDS progression.
ABSTRACT
Progress of World Health Organization (WHO) reclassification of myelodysplastic syndromes (MDS) in the 57th American Society of Hematology annual meetings were reviewed. A revision to the 4th edition of the WHO classification of MDS will be enacted in mid-2016. Based on recommendations of the Clinical Advisory Committee, proposals for change included abandoning the routine names of 'refractory anemia/cytopenia', expressing the prognostic significance of gene mutations in MDS, revising the diagnostic criteria for MDS entities with ring sideroblasts based on the detection of SF3B1 mutations, modifying the cytogenetic criteria for MDS with isolated del (5q), reclassifying the erythroid/myeloid type of acute erythroleukemia, and recognizing the familial link in some cases of MDS.
ABSTRACT
Research progress of somatic mutations and the response to the treatment of de novo myelodysplastic syndromes (MDS) patients in the 57th American Society of Hematology (ASH) annual meetings was reviewed. The optimal methods and therapy time for patients with high-risk de novo MDS remained an area of ongoing investigation. The clinical prognostic scoring system does not include the molecular genetic abnormalities and DNA metlylation of histone/nuclear chromatin modifications, which may predict the effect of hypomethylation (HMA). Treatment of HMA may change the expression of genes related with prognosis, and the response rate to the HMA treatment was significantly increased for TET2-mutated patients with high-variant allele frequencies. The overall grade of recommendation for choosing HMA therapy over induction chemotherapy in high-risk MDS based on molecular genetic mutations was 2C, according to less-associated toxicity and increased responses primarily in TET2-mutated disease. Further prospective studies are needed to evaluate the long-term effects of HMA therapy, particularly in TET2-mutated patients.
ABSTRACT
As an energy dependent membrane transporter, P-GP highly expresses in the organs which have the function of barrier and secretory.In the brain, P-GP mainly expresses in the cerebral vascular endothelial cells of blood brain barrier.In the state of brain injury diseases ( such as epilepsy and cerebral ischemia) , P-GP appears in the hippocampus, cortex and striatum of rat brain.At cellular level, it mainly exists in the cerebral vascular endo-thelial cells and also overexpresses in the neurons and glial cells.