Pharmacokinetics of Recombinant Human Coagulation Factor Ⅷ Preparations in Patients with Severe Hemophilia A / 中国实验血液学杂志

OBJECTIVE@#To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients.@*METHODS@#A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated.@*RESULTS@#The median age of 42 patients with severe hemophilia A was 31（16-50） years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05).@*CONCLUSION@#Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.

Research Progress of Next Generation Sequencing in Acute Leukemia --Review / 中国实验血液学杂志

With the advent of precision medicine, next-generation sequencing (NGS) is playing an increasingly important role in clinical oncology diagnosis and treatment with its advantages of high sensitivity, high accuracy, high efficiency and operability. NGS reveals the genetic characteristics of acute leukemia(AL) patients by screening for specific disease-causing genes to identify occult as well as complex genetic mutations in patients with AL, leading to early diagnosis and targeted drug therapy for AL patients, as well as to predict disease recurrence by detecting mnimal residual disease (MRD) and analyzing mutated genes to determine patient prognosis. NGS plays an increasingly important role in the diagnosis, treatment and prognosis assessment in AL, providing a direction for the pursuit of precision medicine. This paper reviews the research progress of NGS in AL.

A new cinnamic acid ester derivative from Liquidambaris Resina / 中国中药杂志

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.

The Role of Platelet Exosomes in Atherogenic Thrombosis --Review / 中国实验血液学杂志

Exosomes are subtypes of extracellur vesicles containing a variety of cell-specific proteins, lipids and nucleic acids released during cell activation or apoptosis, and play the role of intercellur communication mediators in different physiological and pathological processes. With the development of research in recent years, the role of platelet-derived exosomes in cardiovascular diseases has attracted extensive attention. This paper reviews the role of platelet-derived exosomes in atherosclerotic thrombosis and the potential role of platelet-derived exosomes as biomarkers for the diagnosis and treatment of atherosclerotic thrombotic disease and the problems to be solved.

Establishment of high-resolution bioassay profiling platform to screen α-glucosidase inhibitors from Malus hupehensis / 药学学报

italic>α-Glucosidase inhibitors play an important role in the treatment of diabetes. This study established a high-resolution bioassay profiling platform for rapidly screening α-glucosidase inhibitors in natural product extracts. Five α-glucosidase inhibitors were identified from Malus hupehensis, namely, 3-hydroxyphloridzin, quercetin-3-O-β-D-glucopyranoside, phloridzin, avicularin and quercitrin. The establishment and successful application of this platform provides a powerful tool for the efficient discovery of anti-diabetic active ingredients in complex systems.

Reversal of Drug Resistance in K562/ADM Cells Caused by RA and the Related Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of ursane triterpenoids 3β,19α-dihydroxyursu-12-ene-23,28-dicarboxylic acid (Rotundioic acid, RA) on the sensitivity of adriamycin-resistant K562 cells (K562/ADM Cell) anti-tumor drug, and to explore the effect and mechanism of RA on the multidrug resistance of K562/ADM cells.@*METHODS@#CCK-8 method was used to detect the effect of RA on the sensitivity of K562 cells and K562/ADM cells to anti-tumor drug. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression level of mRNA and the protein in K562 and K562/ADM cells, and the effect of RA on the expression of MDR1 mRNA and P-gp in K562/ADM cells was also detected; Western blot was used to detect the expression of p-JNK, p-p38 and p-ERK1/2 in K562/ADM cells.@*RESULTS@#RA could increased the sensitivity of K562/ADM cells to adriamycin(the reversal factor was 1.61 times), the difference showed statistically significantly (P<0.05); the resistance factor of K562/ADM to ADM was 41.76 times. The expression of MDR1 mRNA in K562 cells was extremely low, and the protein product P-glycoprotein (P-gp) was almost not expressed; MDR1 mRNA and P-gp in K562/ADM cells were highly expressed; RA could down-regulate the expression levels of MDR1 and P-gp in K562/ADM cells. In addition, RA could upregulate the phosphorylation levels of p38 and ERK1/2 in K562/ADM cells, but it has no effect on the expression of p-JNK.@*CONCLUSION@#RA may participate in the regulation of MAPK signaling pathway by upregulating the expression levels of p-p38 and p-ERK1/2 in K562/ADM cells, and thus inhibit the transcription and translation levels of MDR1, and finally reverse the multidrug resistance of leukemia cells.

Epidemiological investigation and drug resistance analysis of Escherichia coli infection from 2014 to 2019 / 公共卫生与预防医学

Objective To investigate the epidemiological characteristics and drug resistance of Escherichia coli infection in Chengdu Second People's Hospital from 2014 to 2019. Methods The specimen types, department sources, infection sites and population characteristics of 1 999 strains of Escherichia coli isolated from the hospital from 2014 to 2019 were analyzed. The trend χ2 was used to analyze the annual isolation rate of Escherichia coli and the change of the rate of Escherichia coli resistance to common antibacterial drugs. Results The isolation rate of Escherichia coli showed a downward trend year by year from 2014 to 2019 (P2trend=16.345, χ2trend=10.697, χ2trend=7.324, P<0.05). Conclusion From 2014 to 2019, the isolation rate of Escherichia coli had a downward trend year by year, but the drug resistance rate of Escherichia coli to ampicillin, piperacillin and ceftriaxone showed an upward trend year by year. In addition to strengthening the monitoring of high-risk sites, departments and population, drug sensitivity tests should also be done to guide rational clinical use.

New Advances in the Treatment of Primary Central Nervous System Lymphoma--Review / 中国实验血液学杂志

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma outside the lymph nodes. At present, high-dose chemotherapy based on methotrexate is the standard induction therapy for newly diagnosed PCNSL, but the effective therapy of relapse/refractory and elderly PCNSL is still unclear. With the progress of clinical trials, new drugs and combined treatment method appear constantly, such as rituximab and ibrutinib, the remission rate of refractory and relapsed patients increased, while lenalidomide showed a good activity in the maintenance treatment of elderly patients. This review summarized briefly the recent advances of research on immunocheckpoint inhibitors, immunoregulatory agents, bruton tyrosine kinase (BTK) and PI3K/AKT/mTOR pathway inhibitors.

The investigation and prognosis in patients with non-alcoholic fatty liver disease and coronary vulnerable plaque / 中华内科杂志

Objective:To investigate the prevalence and prognosis of non-alcoholic fatty liver disease (NAFLD) complicated with coronary vulnerable plaque (VP).Method:Consecutive patients were included who had undergone coronary artery CT angiography (CCTA) from January 1, 2011 to January 30, 2015 at the First People′s Hospital of Neijiang. NAFLD was diagnosed according to the liver imaging findings (liver/spleen CT ratio≤1.0) and clinical data. Baseline data, diagnosis, vulnerable plaque were recorded and followed up. The end points included all-cause death rate, cardiac death rate, non-fatal myocardial infarction rate, and elective coronary revascularization rate.Result:A total of 1 069 patients were eventually recruited in this study, including 316 (29.6%) cases diagnosed as NAFLD. In patients with NAFLD, 130 (41.1%) cases had vulnerable plaque, which was significantly higher than 217 of 753 non-NAFLD patients (28.8%) ( P<0.01). The percentages of spotty calcification, low attenuation plaque, positive remodeling and napkin ring sign in NAFLD cohort were 36.5%, 14.2%, 17.6% and 6.8% respectively, while those corresponding in non-NAFLD cohort were 18.4%, 6.3%, 5.8% and 3.2% respectively. The proportion of each vulnerable feature in NAFLD cohort was significantly higher than that in the non-NAFLD cohort, with P values of 0.016, 0.028, 0.019 and 0.042, respectively. The cardiac mortality rate in NAFLD group was significantly higher than and that of non-NAFLD group (7.0% vs. 3.6%, P=0.044). Multivariate Cox analysis suggested that NAFLD was not an independent risk factor for cardiac death. NAFLD subgroup ( n=316) was divided into VP positive group (NAFLD+VP+, n=130) and VP negative group (NAFLD+VP-, n=186). The mean follow-up time was 4.6±1.3 years. All-cause mortality rate, cardiac death rate, elective coronary artery reconstruction rate, non-fatal myocardial infarction rate in NAFLD+VP+group were 20.8%, 12.3%, 25.4%, 13.8% respectively, which were significantly higher than those corresponding rates in NAFLD+VP-group (5.9%, 3.2%, 8.6%, 6.5%) ( P<0.01, 0.002,<0.01, and 0.032 respectively). Conclusion:The incidences of cardiac mortality, elective coronary revascularization, and non-fatal myocardial infarction are significantly higher in patients with NAFLD than those without. NAFLD combined with vulnerable plaque of coronary arteries predicts worse prognosis.

Advances in chromatography-based methods for screening active compounds from natural products / 药学学报

Natural products have been a major source of leading compounds in drug discovery. How to effectively screen active compounds from complex matrix remains an interesting topic. In this review, we comprehensively summarized advanced liquid chromatography based approaches in natural products screening, including pre-column, on-column and post-column screening methods. Their advantages, disadvantages and prospect are also discussed.

Expressing of linc-223 and miR-125a in Patients with Acute Leukemia and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To determine the expression level of linc-223 and miR-125a in the patients with adult acute leukemia (AL) and explore the relationship between the expression level and the occurrence, development, prognosis of leukemia.@*METHODS@#Bone marrow samples of 93 patients with AL treated in our hospital from January 2017 to September 2017 were enrolled, including 21 cases of acute lymphoblastic leukemia (ALL) and 72 cases of acute non-lymphocytic leukemia (ANLL). At the same time, bone marrow samples from 20 cases of non-malignant hematopathy patients in the same period were enrolled as control group. Real-time quantitative PCR (qRT-PCR) was used to test the expression level of linc-223 and miR-125a in bone marrow of 93 AL patients and the relationship between the level and the occurrence, development, prognosis of leukemia was analyzed.@*RESULTS@#There was no significant difference in the expression of linc-223 between AL patients (ANLL and ALL) and control group (P>0.05). Moreover, there was no significant correlation between linc-223 and PML-RARα gene or the remission rate of patients after treatment. The expression of miR-125a in ANLL patients was significantly lower than those in the control group (P0.05), and also for ALL and control group (P>0.05). In the newly treatment ANLL patients, the expression level of miR-125a showed negatively correlated with LDH level and the ratio of immature cells (r=-0.454, r=-0.400), but not with sex, degree of risk, peripheral blood leukocyte count, platelet count, hemoglobin content, WT1, CRP, etc. (P>0.05). There was a positive correlation between linc-223 and miR-125a in ANLL patients (r=0.296).@*CONCLUSION@#No abnormal expression of linc-223 was found in the bone marrow of AL patients, but miR-125a expression shows a low level and positively correlate with the expression level of linc-223 in ANLL, which is helpful for the diagnosis.

A new phenolic compound from endophytic fungus Aspergillus fumigatus of Euphorbia royleana / 中国中药杂志

This research was carried out to study the secondary metabolites of endophytic fungus Aspergillosis fumigatus from Euphorbia royleana. The endophytic fungus A. fumigatus was fermented by solid fermentation,and purified by various chromatographic methods after extraction. The structures of the compounds were identified by1 H-NMR,13 C-NMR and HSQC,HMBC spectra and physicchemical properties. Three compounds were isolated and their structures were identified as 3-( 3,4-dihydroxybenzoyl)-5-( 3,4-dihydroxyphenyl)-6-methyl-5,6-dihydro-2 H-pyran-2-one( 1),hydroxysydonic acid( 2) and 11-hydroxysydonic acid( 3). Compound 1 is a new compound.

Persistence of rabies antibody 3 years after postexposure prophylaxis with 2-1-1 regimen of Vero-cell rabies vaccine for human use and antibody response to two booster doses / 中华疾病控制杂志

Objective To evaluate the antibody persistence following rabies postexposure prophylaxis (PEP) with 2-1-1 regimen and antibody response to two booster doses. Methods A total of 314 healthy volunteers at year 1, year 2, year 3 who had received a complete rabies PEP using 2-1-1 regimen were recruited. Two booster doses of rabies vaccine were inoculated, and blood samples were obtained before and 14 days after two booster doses. Human rabies virus IgG antibody was evaluated by ELISA, and the antibody levels and antibody positive rates were analyzed. Results The antibody GMC of 303 people at year 1, year 2, year 3 after a complete immunization was 1.33 IU/mL, 1.04 IU/mL and 0.72 IU/mL, with an antibody positive rate of 77.78%, 66.67% and 55.56%, respectively. Among 282 people who received 2 doses for booster immunization, the antibody GMC at day 14 of 1 year, 2 year and 3 year immunization group was 16.83 IU/mL, 19.37 IU/mL and 21.05 IU/mL respectively, which was higher than that before booster immunization (t=16.54, P<0.001; t=13.85, P<0.001; t=16.02, P<0.001). The antibody positive rate was 100.00%, 99.00% and 100.00%, respectively. Conclusions The immune persistence of rabies antibody after PEP with antirabies vaccine using the 2-1-1 regimen is good so as to the immune response after 2 doses of booster immunization in 3 years is effective.

Efflect of miR-34a-Tangeted Regulation of HDACI on Apoptosis of AML Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the regulation of miR-34a on HDAC1 expression and its effect on the apoptosis of acute myeloid leukemia (AML) cells.@*METHODS@#miR-34a mimics, miR-34a inhibitor and miR-34a scramble were transfected into HL-60 cells. The effects of miR-34a expression levels on proliferation and apoptosis of HL-60 cell were detected by CCK8 assay and flow cytometry respectively. The expression of HDAC1 protein was assessed by Western blot after regulating miR-34a expression, the 3'UTR of HDAC1 was cloned and ligated to construct a dual luciferase reporter vector, and then the dual luciferase reporter assay was applied to verify the target of miR-34a, the expression vector pcDNA3.1-HDAC1 was constructed, the interaction of miR-34a and HDAC1 was analyzed by reversion test.@*RESULTS@#miR-34a over-expression could inhibit the proliferation of HL-60 cells and induce their apoptosis. Bioinformatics analysis indicated that the HDAC1 was a target gene of miR-34a. Western blot indicated that miR-34a overexpression down-regulated the expression of HDAC1. Dual luciferase reporter assay and reversion test showed that miR-34a could act at the 3-UTR of HDAC1 gene to regulate its expression.@*CONCLUSION@#miR-34a promotes the apoptosis of HL-60 cells via regulating HDAC1 expression.

Advances of Research on Application of Leukemia Xenotransplantation Model--Review / 中国实验血液学杂志

Abstract　　Tumor xenograft model (PDTX) derived from leukemia patients is an animal model in which the leukemia cells or primary cell lines of patients are transplanted directly into immunodeficient mice.The emergence of nude mice and SCID mice opened early xenotransplantation, then the NSG, NOG mice and the improved model and humanized mice based on there mice significantly improves the success rate of transplantation. The late presented transplantation of leukemia LSC and transplantation of patient-derived and induced pluripotent stem cells obtained based on iPSC technology provide new insight for the anderstanding leukemia genesis and development, and the new type humanized mouse model with normal lymphatic hematopoietic reconstruction provides a new platform of leukemia cell therapy and immunotherapy for leukemia therapy. PDTX is an important platform for the study of the pathogenesis and drug resistance mechanism of leukemia, as well as the development of new drugs and individualized treatment. In this paper, the recent progress in the construction and application of models of immunodeficient mice and their models is reviewed.

Research Advances on the Pathogenesis of Primary Immune Thrombocytopenia--Review / 中国实验血液学杂志

Abstract　Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by less than 100×10/L platelet count in peripheral blood. The pathogenesis of ITP is complex and has not been fully elucidated. Currently, researches on the pathogenesis of ITP mainly focus on the disorders of humoral immunity and cellular immunity. In recent years, some new progress has been made in the study of this pathogenesis, including the platelet clearance pathway that is not dependent on Fc γ R mediation, the metalloproteinase (ADAM) 10 that can regulate T and B cells, and the abnormal expression of micro RNA in genetic factors. Under the joint action of multiple factors, the imbalance of the immune system in the body leads to the occurrence of ITP. This article reviews the research progress on humoral immunity, cellular immunity and other possible new pathogenesis of ITP in recent years.

Simultaneous Determination of Praeruptorion A and Praeruptorion B in Tongxuan Lifei Pills by UPLC / 中国中医药信息杂志

Objective To establish a method for content determination of praeruptorin A and praeruptorin B in Tongxuan Lifei Pills. Methods UPLC method was adopted. ACE UItra Core Super C18 (75 mm × 2.1 mm, 2.5 μm) was used with methanol-water as the mobile phase, by gradient elute. The flow rate was 0.3 mL/min; The detection wavelength was set at 321 nm; The column temperature was 40 ℃. Results Praeruptorin A and praeruptorin B showed the good linear relationship in the range of 20.48–204.8 ng (r=0.999 7) and 5.158–51.58 ng (r=1.000 0), respectively. The average recoveries were 98.2％ and 100.3％, respectively. Conclusion The method is simple, fast, accurate and reproducible, which can be used to determine the contents of praeruptorin A and praeruptorin B in Tongxuan Lifei Pills.

Research Progress on the Role of Musashi-2 in the Pathogenesis of Malignant Hematologic Diseases-Review / 中国实验血液学杂志

Previous studies have found that Musashi-2 (Msi-2) plays an essential role in regulating the gene expression of stem cell populations by inhibiting or activating the translation, and thus regulates stem cell function. Current research shows that Msi-2 involved in the regulation of a variety of malignant hematological diseases through different mechanisms; moreover abnormally expressed in a variety of malignant hematological diseases and involved in the occurrence, development of a variety of malignant hematological diseases. Further study on the role of malignant hematologic diseases will further clarify the pathogenesis of malignant hematologic diseases, and provide a new basis for the diagnosis and treatment of malignant hematological diseases. In this review, the structure and function of Msi-2 and its relationship with malignant hematologic diseases and its latest research progress are summarized.

Research Progress on miR-125 Family in Malignant Hematologic Diseases-Review / 中国实验血液学杂志

MicroRNAs (miRNAs) are a class of endogenous non-coding single-stranded small noncoding RNAs with the length of 20 to 23 nucleotides. MicroRNA-125 (miR-125) family, which is a highly conserved miRNA family, is consist of miR-125a, miR-125b-1 and miR-125b-2. Accumulating evidence demonstrated that miR-125 can be involved in various physiological and pathological processes in vivo. Importantly, it is closely related with the tumorigenesis and tumor development, including tumor cell proliferation, apoptosis, invasion and metastasis, metabolism and immune response. In malignant hematologic diseases, it is defined either as a oncogene, or as a tumor suppressor gene, even, closely related with the drug resistance in a variety of hematologic malignancies. MiR-125 is expected to become a new therapeutic target. Newly, the research of the relationship between miR-125 family and hematologic malignancies become increasing, including leukemia, lymphoma, multiple myeloma. In this review, the relationship between miR-125 family with malignant hematologic diseases and its latest research progress are summarized.

Research Progress on Role of Inflammasome in Development of Thrombotic Diseases -Review / 中国实验血液学杂志

Inflammasome is a group of polyprotein complexes located in the cytoplasm, its activation can induce the maturation and release of proinflammatory cytokines IL-1β and IL-18, and promote the early atherosclerosis. In the recent years, it is found that the inflammasome is activated in thrombotic deseases, moveover, the activated inflammasome and its activation induced cytokines promote the occurrence and development of thrombolic deseases, and show the unfavaourable effect on prognosis. With further exploration on the mechanisms of thrombotic diseases, the relationship between the inflammasome and thrombotic diseases increasingly become a hot spot of research. This review focuses on the action mechanisms of inflammasome in thrombotic diseases.