Advances of Targeted Therapy for Acute Myeloid Leukemia--Review / 中国实验血液学杂志

Acute myeloid leukemia (AML) has highly heterogeneous clinical manifestations and poor prognosis, and traditional chemotherapy is the main treatment. In recent years, with the in-depth development of next-generation sequencing technology, the treatment of AML is gradually exploring the precise targeted therapy in the direction of molecular biology and immunophenotype. The advent of various small-molecule inhibitors and immune-targeted drugs has brought hope to patients who cannot tolerate intensive chemotherapy or with relapsed/refractory AML. Compared with traditional chemotherapy, targeted therapy has the advantages of significant curative effect and fewer adverse effects. This article reviews the latest research progress of targeted drug therapy for AML.

Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis.@*METHODS@#A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared.@*RESULTS@#The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively.@*CONCLUSION@#Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Screening of natural drug molecules against Fusarium oxysporum of ginseng root rot based on machine learning / 药学学报

italic>Fusarium oxysporum widely exists in farmland soil and is one of the main pathogenic fungi of root rot, which seriously affects the growth and development of plants and often causes serious losses of cash crops. In order to screen out natural compounds that inhibit the activity of Fusarium oxysporum more economically and efficiently, random forest, support vector machine and artificial neural network based on machine learning algorithms were constructed using the information of known inhibitory compounds in ChEMBL database in this study. And the antibacterial activity of the screened drugs was verified thereafter. The results showed that the prediction accuracy of the three models reached 77.58%, 83.03% and 81.21%, respectively. Based on the inhibition experiment, the best inhibition effect (MIC = 0.312 5 mg·mL-1) of ononin was verified. The virtual screening method proposed in this study provides ideas for the development and creation of new pesticides derived from natural products, and the screened ononin is expected to be a potential lead compound for the development of novel inhibitors of Fusarium oxysporum.

Effect of Shuangyu Tiaozhi Decoction on SRB1/CYP7A1/FXR Signaling Pathway in Liver of Hypercholesterolemic Rats / 中国实验方剂学杂志

Objective:To observe the effect of Shuangyu Tiaozhi decoction on B-type scavenger receptor （SRB1）/cholesterol 7<italic>α</italic>-hydroxylase protein （CYP7A1）/farnesol X receptor （FXR） signaling pathway in liver of hypercholesterolemic rats， and its mechanism in reducing blood lipid. Method:Among 40 SD rats， 8 were randomly selected as normal group， and the remaining 32 were successfully established as hypercholesterolemic model， and randomly divided into 4 groups： model group， low and high-dose Shuangyu Tiaozhi decoction groups （7.8， 15.6 g·kg^-1）， and simvastatin group （4 mg·kg^-1）， with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol （TC）， triglyceride （TG） and liver TC，free cholesterol （FC） and total bile acid （TBA） were measured. The pathomorphological changes in liver were observed by Hematoxylin and eosin （HE） Staining. The mRNA and protein expressions of SRB1， CYP7A1 and FXR were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. The immunohistochemistry was used to detect CYP7A1 and FXR expressions in liver. Result:Compared with the normal group， TC， TG， FC levels in the model group were significantly increased， while the TBA level was markedly decreased， the morphology showed obvious liver steatosis， and significant declines in expressions of SRB1， CYP7A1， FXR were observed by Real-time PCR， Western blot and immunohistochemistry assays （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the levels of TC，TG，FC in each treatment group were reduced significantly， and the TBA level was increased markedly， the liver steatosis decreased significantly， the results of Real-time PCR， Western blot and immunohistochemistry assays showed significant increase in the expressions of SRB1， CYP7A1， FXR （<italic>P</italic><0.05， <italic>P</italic><0.01）. The therapeutic effect of high-dose Shuangyu Tiaozhi decoction group was more remarkable than that in low-dose Shuangyu Tiaozhi Decoction group （<italic>P</italic><0.05）， with no obvious difference compared with simvastatin group. Conclusion:Shuangyu Tiaozhi decoction can promote hepatic RCT and synthesize bile acid by up-regulating SRB1/CYP7A1/FXR signaling pathway， so as to reduce the blood lipid levels and improve hepatic lipid metabolism of hypercholesterolemic rats.

Effect of Shuangyu Tiaozhi Decoction on NPC1L1 and ABCG8 in Intestine of Hyperlipemic Model Rats / 中国实验方剂学杂志

Objective:To observe the expression levels of niemann-pick C1-like 1 (NPC1L1) and adenosine triphosphate-binding cassette transporters G8 (ABCG8) in intestine of hyperlipidemic model rats, in order to investigate the therapeutic mechanism of Shuangyu Tiaozhi decoction on hyperlipidemia. Method:A total of 40 SD rats were selected, including 8 for normal control group. The remaining 32 rats were used to establish hyperlipemic model. After modeling, the rats were randomly divided into the model group (equivalent normal saline), the high and low-dose Shuangyu Tiaozhi groups (15.6, 7.8 g·kg-1), and the Simvastatin group (4 mg·kg-1), with 8 in each group. They were given drugs by gavage for 8 weeks. The levels of total cholesterol (TC), triglyceride (TG) in serum and total cholesterol (TTC), free cholesterol (FTC) in liver of rats in each group were determined by biochemical and enzymatic methods. The morphological changes of liver were observed by hematoxylin-eosin (HE) staining, and the levels of expressions of NPC1L1, ABCG8 and liver X receptor-α (LXR-α) in intestine were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. The expression of ABCG8 protein was determined by immunohistochemistry. Result:After successful replication of the hyperlipidemia model, the blood lipid level was abnormally increased, and the liver steatosis became obvious in the model group compared with the normal control group. The expression levels of NPC1L1, LXR-α and ABCG8 increased significantly (PPα were significantly down-regulated, but ABCG8 was obviously up-regulated in a dose-dependent manner (PPPPPPConclusion:Shuangyu Tiaozhi decoction can reduce the blood lipid level of hyperlipemic rat model by reducing the absorption of cholesterol. Its mechanism may be correlated with the down-regulation of NPC1L1 expression and the up-regulation of ABCG8 expression.

Protective effect of Angelica polysaccharide on retinal nerve cells in glaucoma rats and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the protective effect of Angelica polysaccharide on the glaucoma-induced retinal neuronal injury, and to elucidate its mechanism. Methods: Eighty-four SD rats were randomly divided into control group, model group, positive drug group, low, middle and high doses of Angelica polysaccharide groups. The model of rat glaucoma was established by sclera sclerotherapy. The intraocular pressures (IOP) of rats in each group were measured. The superoxide dismutase (SOD) activities, malondialdehyde (MDA) contents and nitric oxide (NO) levels in retina tissue of the rats were measured by colorimetric assay. The expression levels of Caspase-3 mRNA and protein in retina tissue of the rats were observed by RT-PCR and Western blotting method. Results: Compared with control group, the IOP of the rats in model group at each time point were significantly increased (P<0. 05); compared with model group, the IOP of the rats in different doses of Angelia polysaccharide groups were significantly decreased (P<0. 05); compared with low dose of Angelica polysaccharide group, the IOP of the rats in high dose of Angelica polysaccharide group was significant decteased (P<0. 05). The levels of MDA and NO in the retina tissue of the rats in model group were higher than those in control group (P<0. 05), but the SOD activities were decreased (P<0. 05); compared with model group, the levels of MDA and NO in retinal tissue of the rats in different doses of Angelica polysaccharide group were significantly decreased (P<0. 05), and the SOD activities were significantly increased (P<0. 05); compared with low dose of Angelica polysaccharide group, the above indexed had significant differences in high dose of Angelica polysaccharide group (P<0. 05). Compared with model group, the expression levels of Caspase-3 mRNA and protein in different doses of Angelica polysaccharide groups were significantly decreased (P<0. 05); compared with low dose of Angelica polysaccharide group, the expression levels of Caspase-3 mRNA and protein were significantly decreased (P < 0. 05). Conclusion: Angelica polysaccharide has protective effect on the retinal tissue of glaucoma model rats, which can decrease the levels of MDA and NO in retina tissue and increase the activity of SOD and decrease the expression levels of Caspase-3 mRNA and protein in retina tissue. It may be one of the mechanisms of polysaccharide protecting in retinal tissue nerve cells.

Protective effect of Angelica polysaccharide on retinal nerve cells in glaucoma rats and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the protective effect of Angelica polysaccharide on the glaucoma-induced retinal neuronal injury,and to elucidate its mechanism.Methods:Eighty-four SD rats were randomly divided into control group,model group,positive drug group,low,middle and high doses of Angelica polysaccharide groups.The model of rat glaucoma was established by sclera sclerotherapy.The intraocular pressures (IOP) of rats in each group were measured.The superoxide dismutase (SOD) activities,malondialdehyde (MDA) contents and nitric oxide (NO) levels in retina tissue of the rats were measured by colorimetric assay.The expression levels of Caspase-3 mRNA and protein in retina tissue of the rats were observed by RT-PCR and Western blotting method.Results:Compared with control group,the IOP of the rats in model group at each time point were significantly increased (P＜0.05);compared with model group,the IOP of the rats in different doses of Angelia polysaccharide groups were significantly decreased (P＜0.05);compared with low dose of Angelica polysaccharide group,theIOP of the rats in high dose of Angelica polysaccharide group was significant decteased (P＜0.05).The levels of MDA and NO in the retina tissue of the rats in model group were higher than those in control group (P＜0.05),but the SOD activities were decreased (P＜0.05);compared with model group,the levels of MDA and NO in retinal tissue of the rats in different doses of Angelica polysaccharide group were significantly decreased (P＜0.05),and the SOD activities were significantly increased (P＜0.05);compared with low dose of Angelica polysaccharide group,the above indexed had significant differences in high dose of Angelica polysaccharide group (P＜0.05).Compared with model group,the expression levels of Caspase-3 mRNA and protein in different doses of Angelica polysaccharide groups were significantly decreased (P＜0.05);compared with low dose of Angelica polysaccharide group,the expression levels of Caspase-3 mRNA and protein were significantly decreased (P ＜ 0.05).Conclusion:Angelica polysaccharide has protective effect on the retinal tissue of glaucoma model rats,which can decrease the levels of MDA and NO in retina tissue and increase the activity of SOD and decrease the expression levels of Caspase-3 mRNA and protein in retina tissue.It may be one of the mechanisms of polysaccharide protecting in retinal tissue nerve cells.

Protective effect of retinal stem cell transplantation on retinal ganglion cells in glaucoma / 中国组织工程研究

BACKGROUND:Stem cel transplantation is a new method for blinding eye disease. But there is a lack of research about the protective effect of retinal stem cel transplantation on retinal ganglion cel s in glaucoma. OBJECTIVE:To explore the protective effect of retinal stem cel transplantation on retinal ganglion cel s of rats with glaucoma. METHODS:Forty-five Sprague-Dawley rats were randomly divided into three groups (n=15 per group) including control, model and retinal stem cel transplantation groups. Rat models of glaucoma were prepared in the latter two groups, and at 7 days after modeling, rats in the three groups were given intravitreal injection of 1 mL retinal stem cel s (5x106 cel s), the same amount of PBS, and no treatment, respectively. Subsequently, relative indicators were detected at 2 weeks after transplantation. RESULTS AND CONCLUSION:The expressions of brain-derived neurotrophic factor and insulin-like growth factor I protein as wel as the number of retinal ganglion cel s were the highest in the control group, fol owed by the retinal stem cel transplantation group model group, and the lowest in the model group (P<0.05). The number of apoptotic retinal ganglion cel s in model group was significantly higher than that of control group (P<0.05), and which in the retinal stem cel transplantation group was significantly lower than that in the model group (P<0.05), but higher than that in the control group (P<0.05). These results suggest that retinal stem cel transplantation for rat glaucoma can exert a protective effect on retinal ganglion cel s.

Clinical outcomes research of use of Shenfu injection based on hospital information system / 中国中药杂志

<p><b>OBJECTIVE</b>To know how Shenfu injection is used in clinical practice and to provide a reference for guiding clinical use of Shenfu injection.</p><p><b>METHOD</b>Extract Shenfu injection's post-marketing re-evaluation data from the hospital information system (HIS) of 20 national grade III-A General Hospitals, use basic statistical analysis methods to analyze Shenfu injection's indications, usage and dosage, treatment course etc. in clinical practice.</p><p><b>RESULT</b>In patients using Shenfu injection, the average age was 62. 15, and patients mainly concentrated in cardiovascular medicine. In clinical practice, Shenfu injection was used mainly for treatment of coronary heart disease (diagnosed as chest obstruction in traditional Chinese medicine). The treatment course mainly ranged from 3 to 7 days, and the dosage was within the limits prescribed by the instruction.</p><p><b>CONCLUSION</b>Shenfu injection was mainly used for elderly patients, and has been used according to instruction in practice almostly.</p>

Study of immunoglobulin and T-cell receptor gene rearrangements in patients with non-Hodgkin's lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements in bone marrow or peripheral blood of patients with non-Hodgkin's lymphoma (NHL), and to explore the potential clinical significance.</p><p><b>METHODS</b>The Ig/TCR gene rearrangements in bone marrow or peripheral blood of 139 NHL patients were analyzed by using BIOMED-2 multiple primers system and Multiplex PCR assay.</p><p><b>RESULTS</b>Ig clonality was detected in 85.4% (70/82) of chronic lymphocytic leukemia (CLL), including 46.3% (38/82) IgH rearrangement, 62.2% (51/82) IgK rearrangement and 1.2% (1/82) IgL rearrangement, and in 39.4% (13/33) of other categories of B-lineage NHL (B-NHL), including 33.3% (11/33) IgH and 39.4% (13/33) IgK rearrangements. TCR clonality was detected in 50.0% (12/24) of all definite T-lineage NHL (T-NHL), including 8.3% (2/24) TCRB and 45.8% (11/24) TCRG, no TCRD was detected. The detection rate of gene rearrangements of NHL diversed in different clinical stages \[36.4% in early stage (Ann Arbor stage I and II) and 45.6% in late stage (III and IV)\] and in different degrees of malignancy (40.0% indolent NHL and 45.6% aggressive NHL), but no obvious statistical significance was obtained (P > 0.05). The detection rate of bone marrow invasions of NHL (except CLL) with examinations of bone marrow smear under the microscope was 12.3% (7/57), much lower than the clonality testing (43.9%, 25/57) (P < 0.05). Sensitivity test showed that the sensitivity of malignant clonality testing by multiplex PCR was 3.12% - 6.25%.</p><p><b>CONCLUSIONS</b>The detection rate of gene rearrangements diverses in different clinical stages and degrees of malignancy of NHL, but the correlation has not been proved in this research. The sensitivity of multiplex PCR-based clonality testing is enhanced with the combination of BIOMED-2 primers system. It is more sensitive than the morphological examinations of bone marrow smear in detecting bone marrow invasions, and may provide a powerful strategy in the routine diagnosis and assessment after treatment.</p>

Detection of gene rearrangement in bone marrow of patients with non Hodgkin's lymphoma by BIOMED-2 protocols / 中国实验血液学杂志

This study was purposed to explore the feasibility of BIOMED-2 protocols for detection of immunoglobin (IG) and T-cell receptor (TCR) gene clonal rearrangement in bone marrow of Non-Hodgkin's lymphoma(NHL) patients, and to evaluate its clinical value. Gene clonal rearrangment (IGH, IGK, IGL, TCRβ, TCRγ, TCRδ) was detected by using BIOMED-2 protocols in 73 bone marrow examples of NHL patients. The PCR results were compared with the cytomorphologic examination of bone marrow. The correlation between PCR detection results and clinical stage, pathological factors were also evaluated. The results showed that clonal IG or TCR gene rearrangements were found in 31 of 73 cases (42.5%), higher than the positive rate of cytological analysis (24.7%, 18/73, p < 0.05). IG/TCR clonality rates were 40.0% (22/55) for B-NHL and 50% (9/18) for T-NHL. IG/TCR clonality rates detected in patients with III/IV stage were higher than those with I/II stage (p < 0.05). It is concluded that BIOMED-2 protocols are effective methods for detection of abnormalities in bone marrow in patients with lymphoma, and are superior to cytomorphologic examination. The positive rate of PCR detection is correlated with Ann Arbor stage, but is not related with malignant degree, age, treatment status, B symptoms or the involvement of spleen.