Establishment and evaluation of a method for phages enrichment by ferric trichloride-polyvinylidene fluoride membrane filter / 中华预防医学杂志

Objective: To establish and evaluate a method of enriching bacteriophages in natural water based on ferric trichloride-polyvinylidene fluoride (FeCl3-PVDF)membrane filter. Methods: Based on the principle of flocculation concentration, the method of recovering bacteriophage from water sample was established by using iron ion flocculation combined with membrane filter. The titer of phage was determined by Agar double layer method. The recovery efficiency of phage was detected by phage fluorescence staining and real-time fluorescence PCR reaction. Water samples from different sources were collected for simulation experiment to evaluate the enrichment effect. At the same time, the sewage discharged from hospitals was taken as the actual water sample, and the common clinical drug-resistant bacteria were used as the host indicator bacteria to further analyze the enrichment effect of FeCl3-PVDF membrane filter rapid enrichment method on the bacteriophage in natural water samples. Results: The method of enrichment of bacteriophages in natural water by iron ion concentration 50 mg/L and PVDF membrane filter was established. The recovery rate of this method for bacteriophage was 93%-100%. Under the multi-functional microscope, it was found that the bacteriophage of the enriched water sample increased significantly and the fluorescence value of the enriched water sample determined by the enzyme labeling instrument was about 13 times as high as that before enrichment. After concentration of the actual water samples from the hospital drainage, the positive rate of bacteriophage isolation in the concentrated group and the non-concentrated group was 23% and 4%, and the fluorescence value in the concentrated group was 2-24 times as high as that of the non-concentrated group. Conclusion: The method of FeCl3-PVDF membrane filter is a simple, efficient and rapid method for enriching bacteriophages in different water samples.

Short-term effects and seasonal variation of ozone on daily hospital outpatient visits for childhood asthma in Lanzhou / 北京大学学报(医学版)

OBJECTIVE@#To analyze the effects of ozone (O3) concentrations measured with different approaches across different seasons on the total number of childhood asthma-related clinical visits, as well as the differentiation of such effects across different groups of patients.@*METHODS@#The outpatient data of three grade A tertiary hospitals in Lanzhou City spanning from 1 January 2014 to 31 December 2017, as well as air pollution and meteorological data during the same period were collected. Considering the nonlinear relationship between O3 concentrations and the total number of childhood asthma-related clinical visits and meteorological factors, a generalized additive temporal sequence model was employed to analyze the short-term association between changes in O3 concentrations and the total number of childhood asthma-related clinical visits. Taking into account of the variations in O3 concentrations within 1 day, this study adopted different measurement approaches to address the three types of O3 exposures, namely, the maximum 1 h daily concentration (O3max1h), the maximum 8 h daily concentration (O38h) and the mean 24 h daily concentration (O324h) as the short term exposure indicators to O3, followed by a model-based analysis.@*RESULTS@#The increase in short-term exposure levels to O3 in summer had a significant effect on the increase in the total number of childhood asthma-related clinical visits. With lag0 for the current day, every 10 μg/m3 increase in atmospheric concentration of O3max1h was associated with an increase in the total number of childhood asthma-related clinical visits by 3.351% (95%CI: 1.231%-5.516%); for every 10 μg/m3 increase in O38h concentration, the total number of childhood asthma-related clinical visits increased by 3.320% (95%CI: 0.197%-3.829%); for every 10 μg/m3increase in O324h concentration, the total number of childhood asthma-related clinical visits in summer increased by 6.600% (95%CI: 0.914%-12.607%); moreover, an increase in exposure to O3max1h also led to a significant rise in the total number of childhood asthma-related clinical visits among the males.@*CONCLUSION@#The increase in short-term exposure levels to O3 in summer in Lanzhou City has a significant effect on the increase in the total number of childhood asthma-related clinical visits; O3max1h is more closely correlated with the increase in the total number of childhood asthma-related clinical visits.

Analysis of Proliferation Characters of Bone Marrow Mesenchymal Stem Cells Derived from Patients with Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To analyze the proliferation potential of bone marrow-derived mesenchymal stem cells (MSC) in patients with myelodysplastic syndrome (MDS).@*METHODS@#The MSC derived from the 24 patients with newly diagnosed MDS (MDS-MSC group) and MSC derived from 15 patients with nutritional anemia (control group) in the Affiliated Hospital of Hebei University were used as the research objects. The proliferation potential of MSC was analyzed by colony-forming unit assay, doubling time, cumulative passaging, cell number after 10 days of culture with equal amount of MSC and MTT experiment. The mechanism of abnormal proliferation was analyzed by cell cycle experiment, apoptosis experiment and p21 gene expression assay.@*RESULTS@#In the colony forming unit assay, the number of MDS-MSC colonies was 4.44±2.51, which was significantly lower than that of the control group (12.44±2.55)(P<0.01); the doubling time of MDS-MSC group was significantly longer than that of the control group (7.80±3.26 vs 3.63±0.85) (P<0.01); the number of MDS-MSC in 5×10@*CONCLUSION@#The proliferative capability of MDS-MSC is significantly reduced, which relates with the arrest of cell cycle in G

Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19~+B cells regulating FAK/CAPN/PI3K pathway / 中国中药杂志

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.

Research progress on culture technologies,chemical components,and pharmacological activities of Saussurea involucrata cells / 中国中药杂志

Saussurea involucrata,a traditional Chinese medicinal material,is effective in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome,cold pain in lower abdomen,and menstrual irregularities. However,due to the specific habitat,low natural reproduction rate,slow growth,and overexploitation,it is at the high risk of extinction. S. involucrata cells can be obtained through callus culture,suspension culture,and hairy root culture. This study highlighted the influences of reactor type,culture system,precursor,elicitor type, and light wavelength on the suspension culture of S. involucrate cells. The chemical components of S. involucrata cells mainly include phenylpropanoids,flavonoids,lignans,and steroids,among which phenylpropanoids are the most abundant. S. involucrata cells have multiple pharmacological activities of anti-inflammation,analgesia,activating blood and resolving stasis,immunoregulation,increasing bone density,lowering blood lipids,anti-hypoxia,anti-exercise fatigue,anti-radiation,anti-obesity,and anti-oxidation. Moreover,it has the potential of treating aplastic anemia. This study reviews the cell culture technologies,chemical components,and pharmacological activities of S. involucrata cells,laying a basis for the further research,development,and utilization.

Mouse strain-specific responses of mitochondrial respiratory function and cardiac hypertrophy to isoproterenol treatment / 生理学报

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O

Research Advances on the Senescence Mechanism of Bone Marrow Mesenchymal Stem Cells Derived from Patients with Myelodysplastic Syndrome--Review / 中国实验血液学杂志

Emerging data have demonstrated that bone marrow mesenchymal stem cells (MSCs) play important roles in the progression of myelodysplastic syndrome (MDS). Experiments in vitro have showed that MSCs derived from MDS patients (MDS-MSC) exhibit the biological characteristics of cell senescence. Although the underlying mechanisms that regulate cell senescence need to be further elucidated, existing researches indicate that the mechanisms of MDS-MSC senescence have significant heterogeneity. Depth understanding of the underlying mechanisms involved in cell senescence of MDS-MSC are crucial to explore the potential therapeutic target of MDS. Therefore, this review summarizes research advances related with MSC senescence, such as MDS-MSC intrinsic changes in telomere shortening, DNA methylation status, oxidative stress and signal pathways regulating cell senescence in recent years.

JYD01, a newly synthesized diterpenoid derivative, induces apoptosis in human gastric cancer cells through detaching hexokinase II from mitochondria / 中国药理学通报

Aim To investigate the effect of JYD01, an ent-kaurane diterpenoid analog, on detaching hexokinase II (HK II) from mitochondria, and discuss the underlying mechanism of anti-gastric cancer cell proliferation. Methods MTT assay was performed to measure the effect of JYD01 on the growth capacity of human gastric cancer cell lines MGC-803 and BGC-823. The glycolysis of MGC-803 cells in response to JYD01 was analyzed using a Seahorse XFp extracellular flux analyzer by real-time measurements of the extracellular acidification rate (ECAR, indicative of glycolysis). The effect of JYD01 in mitochondrial membrane potential (MMP) and apoptosis was observed by a fluorescence microscopy. The apoptotic rate and the quantitative analysis of MMP falling of cell lines treated with JYD01 were analyzed by flow cytometry. The proteins were determined by Western blot. Results JYD01 observably inhibited the growth of MGC-803 and BGC-823 cells in a dose-dependent manner. JYD01 induced a dose-dependent detachment of HK II from mitochondria of MGC-803 cells, effectively reduced glycolysis, and caused the drop of MMP leading to the release of cytochrome c. 1, 2 and 4 μmol · L

Rabbit skull defects repaired by the hydroxyapatite/geltin scaffold combined with bone marrow mesenchymal stem cells and umbilical vein endothelial cells / 中国组织工程研究

BACKGROUND: Hydroxyapatite-geltin composite has good biocompatibility and osteoinductivity, and can used be as tissue engineering scaffold to repair bone defects. OBJECTIVE: To observe the effect of three-dimensional (3D) printed hydroxyapatite/gelatin scaffold combined with bone marrow mesenchymal stem cells and umbilical vein endothelial cells in repairing rabbit skull defects. METHODS: Nine male New Zealand white rabbits were taken to establish a skull defect model with a diameter of approximately 0.8 cm, and randomly divided into three groups: blank group: no any treatment; control group: only 3D printed hydroxyapatite-geltin scaffold; experimental group: 3D printed hydroxyapatitegeltin scaffold and bone marrow mesenchymal stem cells and bone marrow mesenchymal stem cells complex group, with three rabbits in each group. At 8 weeks after the operation, CT scan of the skull pyramid beam and histological observation of the skull defect were performed on the white rabbits of each group. Animal experiments were approved by the Ethics Committee of Jining Medical College. RESULTS AND CONCLUSION: (1) CT scan of pyramidal tract: Blank group showed obvious bone defects, and the defect area was slightly radiopaque with the edges of the surrounding normal bone tissue. Control group showed some new bone formation, which was discontinuous and inconsistent with the surrounding bone tissue. Experimental group showed that the new bone tissue was linear and continuous; the thickness was thin; and the defect area merged with the adjacent bone tissue edge. (2) Histological observation: Hematoxylin-eosin staining and Masson trichrome staining showed that fibrous connective tissue formation and a small amount of free bone cells were seen in the defect area of the blank group. A small amount of bone formation was seen in the control group. Bone matrix was deposited at the edge of the material, replacing the material to form small bone trabeculae. The material space of the experimental group was gradually replaced by new bone, and the defect area was filled with new bone and trabecular bone structure-like tissue. (3) The results show that the 3D bionic printing hydroxyapatite-geltin scaffold combined with bone marrow mesenchymal stem cells and bone marrow mesenchymal stem cells can effectively promote the growth of bone tissue and accelerate the repair of bone defects.

Thyroid function reference ranges during pregnancy in a large Chinese population and comparison with current guidelines / 中华医学杂志(英文版)

BACKGROUND@#A correct thyroid function reference range is important for the accurate diagnosis of thyroid disease during pregnancy. However, there is no consensus on whether thyroid function reference ranges in Chinese population should follow the America Thyroid Association (ATA) guidelines. This study aimed to establish a thyroid function reference range more suited to the Chinese population by evaluating the current thyroid function reference range in pregnant Chinese women and comparing it to the ATA guidelines.@*METHODS@#A total of 52,027 pregnant women were enrolled from January 2013 to December 2016. Thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels were tested during the first and third trimesters of pregnancy. Reference ranges of TSH and FT4 were established from the 2.5th and 97.5th percentiles of the TPOAb-negative population of women. The Mann-Whitney U test was used to compare thyroid hormones between the TPOAb-positive and TPOAb-negative groups.@*RESULTS@#We obtained that the TSH reference ranges were 0.03 to 3.52 mU/L and 0.39 to 3.67 mU/L, and the FT4 reference ranges were 11.7 to 19.7 pmol/L and 9.1 to 14.4 pmol/L, in the first and third trimester, respectively. If we used the 2011 ATA criteria about 7.0% and 4.0% pregnant women would be over diagnosed in first and third trimester, respectively, compared with local population thyroid hormone reference. When we compared our local criteria with the new 2017 ATA criteria, about 1.2% and 0.8% pregnant women would have a missed diagnosis in first and third trimester, respectively.@*CONCLUSIONS@#Based on our data, which is in line with the current ATA guidelines, a population-based thyroid function reference range would be the first choice for diagnosis of thyroid disease during pregnancy in China. In case such population-based thyroid function reference ranges are unavailable in the east of China, our reference ranges can be adopted, if the same assay is used.@*TRIAL REGISTRATION@#www.chictr.org.cn (No. ChiCTR1800014394).

Lentivirus-mediated BMP-2 overexpression plasmid transfection into bone marrow mesenchymal stem cells combined with silk fibroin scaffold for osteoblast transformation / 中国骨伤

OBJECTIVE@#To explore the effect of lentivirus-mediated BMP-2 overexpression plasmid transfection into bone marrow mesenchymal stem cells and silk fibroin scaffold on osteoblast transformation.@*METHODS@#The lentivirus BMP-2 overexpression vector was constructed, bone marrow mesenchymal stem cells were cultured, and the combined culture system of nuclear scaffolds was constructed. Alizarin red staining and alkaline phosphatase staining were used to detect the osteogenic transformation of bone marrow mesenchymal stem cells in vitro. Ten New Zealand white rabbits, weighing 3.2 to 4.5 kg(averaging 3.9 kg), aged (2.89±0.45) years old, were selected to construct the rabbit tibial defect model by drilling a conical tibial defect (5 mm in length, 2 mm in width and 3 mm in depth) with an oral drill. The repair of the tibial defect in the animal model was observed by HE staining. The experimental group was implanted with silk fibroin scaffold + BMP-2 overexpression vector bone marrow mesenchymal stem cell complex, while the negative control group was implanted with silk fibroin scaffold+non-transfected bone marrow mesenchymal stem cell complex.@*RESULTS@#Compared with the control group(silk fibroin scaffold+non-transfected bone marrow mesenchymal stem cells), the number of adherent cells on the surface of the scaffold in the experimental group(silk fibroin scaffold+transfected BMP-2 overexpression vector BMP-2 complex) increased significantly. Compared with the control group, the ECM secretion in the experimental group increased significantly. EDX analysis showed that the content of calcium ion was 0.22% in the control group and 0.86% in the experimental group, which showed that the ability of inducing calcium ion formation in the experimental group was stronger than that in the control group. Alizarin red staining of calcium nodules showed that there was no obvious change in the naked eye of the control group, and a small amount of calcium nodules could be seen under the microscope. In the experimental group, obvious red area staining was observed by naked eye, and a large number of calcium nodules were observed by microscopy. The results of alkaline phosphatase staining showed that there was no obvious change in the naked eye of the control group, and no obvious change in the microscopic observation. In the experimental group, purple area staining was observed by naked eyes, and ALP staining was strongly positive by microscopy. The combined culture system of silk fibroin scaffold and bone marrow mesenchymal stem cells can repair cartilage defects. The repair effect of BMP-2 bone marrow mesenchymal stem cells after transfection is obviously better than that of non-transfection group. HE staining showed that inflammatory cells decreased and scaffolds disappeared slightly in the control group. In the experimental group, inflammatory cells were significantly reduced, scaffolds disappeared and angiogenesis was observed.@*CONCLUSIONS@#Lentivirus-mediated BMP-2 overexpression plasmid can promote BMSC to differentiate into osteocytes and secrete more extracellular matrix containing Ca²⁺ to promote bone defect repair.

Jar-TTA, a natural diterpenoid derivatives, induces apoptosis in human esophageal cancer cells through dual inhibition of glycolysis and oxidative phosphorylation / 中国药理学通报

Aim To investigate the effects of Jar-TTA in dual inhibition of glycolysis/oxidative phosphoryla-tion in human esophageal cancer cells and explore the related molecular mechanism. Methods The effect of Jar-TTA on the esophageal cancer cell EC 109 and KYSE-150 viability was examined using MTT assay. The effect of Jar-TTA in apoptosis morphology and mitochondrial membrane potential ( MMP) was observed by a fluorescence microscopy. The apoptosis of cell lines treated with Jar-TTA, the quantitative analysis of MMP falling, as well as the glucose uptake was ana-lyzed by flow cytometry. The mitochondrial OXPHOS and glycolysis of EC 109 cells in response to Jar-TTA were analyzed using a Seahorse XFp extracellular flux analyzer by real-time measurements of the oxygen consumption rate (OCR, indicative of mitochondrial OXPHOS) and extracellular acidification rate(ECAR, indicative of glycolysis). The expression of the proteins related with glycolysis were detected by Western blot. Results Jar-TTA caused strong antiproliferation in EC 109 and KYSE-150 cells in a concentration-dependent manner. 2 , 4 and 8 jimol • L"1 Jar-TTA treat-ments of EC 109 cells for 24 h resulted in a significant increase of early apoptosis population up to (27. 9 ± 6. 1)%, (71.1 ±9.3)% and (65. 0 ±9.5)%, respectively , compared to control treated cells (5. 6 ± 3.2)%. The mitochondrial OXPHOS and glycolysis were significantly inhibited in EC 109 incubated by 4 and 8 p,mol • L"1 Jar-TTA for 2 h. In addition, Jar-TTA induced the drop of MiMP. Furthermore, the glucose uptake and the expression of GLUT4 and LDHA were distinctly inhibited in EC 109 treated by Jar-TTA. Conclusions Jar-TTA induces apoptosis of human e-sophageal cancer cells through dual inhibition of glycolysis and oxidative phosphorylation, which is related with the drop of MMP collapse, the decrease of glucose uptake and the down-regulation of GLUT4 and LDHA in EC 109 treated by Jar-TTA.

Comparison of the phagocytosis and inflammatory response of murine macrophages infected by Leptospira strains 56606v and 56606a / 上海交通大学学报（医学版）

Objective : To compare the response and consequence of mouse macrophages infected by Leptospira interrogans 56606v and 56606a, and explore the mechanisms of pathogenic Leptospira to cause disease. Methods: Peritoneal macrophages of C57BL/6 mice were infected by pathogenic Leptospira 56606v and non-pathogenic Leptospira 56606a respectively. Immunofluorescence staining was performed to observe phagocytosis and clearance of Leptospira after infection, and realtime-PCR was used to determine cytokine production of macrophages. Results: After 72-hour infection, strain 56606v exhibited a lower phagocytic rate but survived after incubation with peritoneal macrophages compared with strain 56606a, which showed a higher phagocytic rate but was cleared at that time point. Additionally, cytokine production of macrophages incubated with 56606v was lower than that with 56606a. Conclusion: Leptospira interrogans strain 56606v can survive in macrophages, which may contribute to evasion from phagocytic clearance and lead to disease, while strain 56606a can be cleared, which implicates a lower pathogenicity.

Predicting Therapeutic Response by Lymphocyte Level at 28th Day after DAC Treatment in Patients with MDS / 中国实验血液学杂志

OBJECTIVE@#To investigate a reliable clinical indication for predicting the therapeutic response of decitabine therapy in the patients with myelodysplastic syndromes (MDS).@*METHODS@#The clinical efficacy of decitabine for 55 cases of MDS was analyzed retrospectively. According to the lymphocyte level at d28 after the first time treatment with decitabine, the patients were divided into high lymphocyte level group (H-Lym≥1.2×10/L) and low lymphocyte level group (L-Lym<1.2×10/L), and the overall response rate (ORR) and the progression-free survival (PFS) time in 2 groups were compared.@*RESULTS@#As compared with L-Lym group, the ORR and PFS time in H-Lym group were significantly enhanced ［(76.0% vs 50.0%) (P<0.05) and median time (15.7 months vs 8.5 months)(P<0.05), respectively］;the ratio of platelet level ≥100×10/L in H-Lym group was very significantly higher than that in L-Lym group (72.0% vs 20.0%)(P<0.01). Multivariat analysis showed that the risk of disease progression in L-Lym group was 4.45-fold of H-Lym group (95% CI:1.58-12.59)(P<0.05).@*CONCLUSION@#The patients with lymphocyte level ≥1.2×10/L at day 28 after the first time treatment with decitabine show the higher ORR and longer PFS time, therefore. the lymphocyte level at day 28 after first time treatment with decitabine can be used as an early clinical indicator for predecting the response to decitabine treatment.

The absolute value of lymphocyte counts and the response to decitabine treatment in patients with myelodysplastic syndrome / 解放军医学杂志

Objective To investigate the relations of absolute lymphocyte counts (ALC) to the therapeutic responses in patients with myelodysplastic syndrome (MDS) after the first course of decitabine (DAC) treatment.Methods Clinical data of 35 patients with MDS and MDS-derived secondary acute myeloid leukemia (AML) who were admitted in the Affiliated Hospital of Hebei University from Jan.2014 to Dec.2016 and treated with DAC were included in the present study.The patients were grouped into high lymphocyte group (H-Lym,ALC ≥ 1.2 × 109/L) and low lymphocyte group (L-Lym,ALC＜1.2 × 109/L) based on the ALC in days 28-35 after the first course of DAC treatment.The baseline data of both groups were compared with Pearson x2 analysis,while t test was used to analyze the changes of lymphocyte number before and after the first course of DAC treatment.Progressionfree survival (PFS) was estimated with Kaplan-Meier method,and the cumulative survival (CS) was compared between the two groups using log-rank test.Results Of the 35 patients,15 were in H-Lym group and 20 in L-Lym group.No significant difference existed in the baseline lymphocyte levels between the two groups (P＞0.05).The statistically significant differences (P＜0.05) existed only in the patients of the two groups who were with the proportion of bone marrow blasts ≥ 10％.The ALC in H-Lym group were slightly higher after the first course of DAC treatment than that at the time of diagnosis,but with no statistically significant (P＞0.05).However,the ALC in L-Lym group were significantly lower after the first course of DAC treatment than that at the time of diagnosis (P＜0.05).Patients had higher overall response rate (ORR) in H-Lym group than in L-Lym group (80％ vs.40％,P＜0.05).The median PFS was 10 months in H-Lym group and 7.6 months in L-Lym group (P＜0.05).Univariate analysis showed that the low ALC was a poor prognostic factor for the progression ofMDS (P＜0.05).Conclusion Patients with ALC ≥ 1.2 × 109/L after the first course of DAC treatment will have better ORR and longer PFS.

Research advances of mesenchymal stem cells from bone marrow in myelodysplastic syndrome / 基础医学与临床

Myelodysplastic syndrome (MDS) is definded as a group of clonal hematological malignancies characterized by bone marrow (BM) ineffective.hematopoiesis and increases risk for progression to acute myeloid leukemia. The altered BM mesenchymal stem cells (MSCs) play a pivotal role in the evolution and propagation of MDS. Com-pared to normal MSCs, MSCs in MDS often exhibit altered Cytogenetic, epigenetic, differentiation and functional properties, moreover, high MSCs density is associated with poor prognostic factors, which translated into a signifi-cantly diminished ability to support normal hematopoiesis, facilitates survival of malignant hematopoietic cells, ulti-mately promote disease progression and transform to acute myeloid leukemia.Therefore, characterization of key steps in the pathogenesis of MDS will lead to new approaches to treat patients with this disease.

Quantitative Determination of Arsenic Species in Feed Using Liquid Chromatography-Hydride Generation Atomic Fluorescence Spectrometry / 分析化学

A sensitive and rapid method using liquid chromatography-hydride generation atomic fluorescence spectrometry (HPLC-HG-AFS) was developed for the simultaneous determination of seven arsenic species As3+, As5+,MMA, DMA, p-ASA, 4-OH and ROX in feeds. The isolation of the analytes from feed samples was accomplished using methanol water (1:1, V/V). The target compounds were separated on a PRP-X100 anion exchange column and then analyzed by HG-AFS. The mobile phase was 15 mmol/L (NH4)2HPO4and 10 mmol/L potassium acid phthalate. Good linearity was obtained for all of the seven arsenic species, with linear coefficients higher than 0.9964. The LODs of the seven arsenic species were between 5 and 30 μg/kg. Average recoveries for the seven analytes were in the ranges of 76.3%-108.1%, with intra- and inter-day repeatability lower than 7.7% and 17.4%,respectively. This validated method was successively applied to the determination of arsenic species in feed. This method was sensitive,simple,cheap and low operation cost,and could be used for the determination of the arsenicspecies in feeds.

Exendin-4 alleviates diabetic cardiomyopathy in mice by regulating Sirt1/PGC1α / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism.</p><p><b>METHODS</b>C57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice.</p><p><b>RESULTS</b>Compared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice.</p><p><b>CONCLUSIONS</b>Exendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.</p>

Mechanism and Its Countermeasure of Hypomethylating Agent Resistance in Patients with Myelodysplastic Syndrome--Review / 中国实验血液学杂志

Hypomethylating agents(HMA) currently are widely used in the treatment of myelodysplastic syndromes (MDS), provide a significant improvement in the treatment of MDS. However, resistance to HMA is an almost universal phenomenon. This review was focused on immune effects related to DNA methylation, and to explore the mechanism underlying HMA resistance involved in immune checkpoint pathways. However, the optimal role of checkpoint blockade therapy (CBT) and immune checkpoint pathways remain in HMA failure questionable. The better understanding of immune checkpoint pathways in resistance of HMA offers a compelling rationale to introduce CBT in patients as a novel treatment option. CBT is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies, therefore, may alter the treatment landscape in MDS. The suitability and effectiveness of combining HMA with CBT need to be confirmed by the results of ongoing clinical trials, so as to find novel strategies to improve outcome after failure of HMA.

Lymphocyte Count before First Consolidation Therapy Is A Predictor of Relapse free Survival in Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of absolute lymphocyte count(ALC) before start of the first cycle of consolidation chemotherapy(CC) on the relapse free survival in the patients with acute myeloid leukemia(AML), so as to explore a simple and easy method for predicting AML relapse.</p><p><b>METHODS</b>The clinical data of 132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from 2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated with standard induction chemotherapy (IC) and consolidation chemotherapy (CC). According to lymphocyte count of patients before start of the first cycle of CC, the AML patients were divided into 2 group: high lymphocyte count group (H-Lym≥1.2×10/L) and low lymphocyte count group (L-Lym<1.2×10/L). The differences in ralapse rate and relapse-free survival between 2 groups were analyzed.</p><p><b>RESULTS</b>Among 132 patients with AML, patients who could be valuated and were elicible for the study accounted for 65 (49.24%). The absolute leukocyte count, age, chromosome karyotypes before IC of patients did not show statistical difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate analysis showed that the Low lymphocyte count and unfavorable chromosome karyotypes were poor prognostic factors for the relapse-free survival time, and there was significant difference between 2 groups (P<0.01). The relapse risk in patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98) (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes, this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01).</p><p><b>CONCLUSION</b>The AML patients with high lymphocyte count before the first CC have more long relapse free survival time suggesting that the lymphocyte count before the first CC may be prognostic factor for relapse free survival of AML patients.</p>