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Paraneoplastic autoimmune and inflammatory disorders are often associated with myelodysplastic syndromes (MDS). The etiopathogenesis of MDS-associated autoimmune and inflammatory disorders is still unclear and treatment options are limited. Patients with MDS are at high risk of infections, which can be increased by the use of steroids. In the present study, we report on two patients with MDS-related autoimmune and inflammatory disorders who were in remission and reduced the steroid dose with 5-azacytidine treatment. The first case was a 67-year-old patient diagnosed with MDS and the whole-body erythroderma was the chief complaint. When the patient was treated with decitabine, steroid treatment was needed to control the erythroderma. When we changed decitabine to 5-azacytidine, both his erythroderma and his dependency on the steroid treatment were resolved. The second patient was a 68-year-old man with MDS who presented with Sweet's syndrome. Sweet's syndrome was completely treated after the first cycle of 5-azacytidine. In addition, Sweet's syndrome can occur as an adverse reaction of 5-azacitidine, so we illustrate that it is important to distinguish whether Sweet's syndrome is MDS-related skin disorders or 5-azacitidine-related skin side-effects.

Recent advances in developing soft electronic devices have increased the demand for deformable storage devices. However, the fabrication of microsupercapacitors (MSCs) with satisfactory electrochemical performance and mechanical robustness remains a crucial challenge. In this work, deformable moisture-activated all-solid-state planar MSCs were designed and fabricated by an in situ laser reduction technology. The planar MSC shows a high areal-specific capacitance (∼4.7 mF cm−2 at 5 mV s−1) under high moisture (RH = 100%). Moreover, the tensile strength of the deformable planar MSC increased to 21 MPa. Moreover, the mechanical robustness of the planar MSC allows them to be folded into origami. The deformable moisture-activated all-solid-state planar MSC holds promises for soft storage devices.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1–G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1–G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7–G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9–G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.

The present study aims to evaluate the clinical application values of ultrasound real-time shear wave elastography (SWE) in the diagnosis and differential diagnosis of cervical cancer (CC).A total of 285 married female patients were screened and divided into three groups according to the results of the pathological examination and the cervical ThinPrep cytologic test: 1) the CC group (n = 94); 2) the cervical intraepithelial neoplasia (CIN) group (n = 91); and 3) the normal control group (n = 100). The maximum Young's modulus (Emax), mean Young's modulus (Emean), minimum Young's modulus (Emin), and Young's modulus stability (Esd) in each group were measured and statistically analyzed.There were no statistically significant differences in Emax, Emean, Emin, and Esd values between the anterior and posterior cervical walls, premenopausal and postmenopausal women, and nonparturient and parturient women in the normal control group. The Emax, Emean, Emin, and Esd values in the CIN group showed no statistically significant differences in different periods when compared with the control group. The differences between the normal control group and the CC group were statistically significant; the CC group showed no statistically significant differences in Emax, Emean, Emin, and Esd values at different clinical stages and in different pathological types. The cutoff value of Emax for CC diagnosis, which was of the highest accuracy (89.7%), was 43.48 kpa.Ultrasound real-time SWE can be applied to CC diagnosis.

To analyze the expression and clinical characteristics of CD68 in bone marrow and peripheral blood of patients with acute myeloid leukemia (AML).The expression of CD68 in bone marrow blast cells was detected by four-color flow cytometry in 50 newly diagnosed AML patients and 23 controls. The expression of CD68 in peripheral blood of 85 newly diagnosed AML patients, 29 remission AML patients and 24 controls was detected by ELISA. The correlation between the expression rate of non-M3 AML bone marrow CD68, peripheral blood CD68 concentration and white blood cell count and other clinical data was compared respectively.The median CD68 expression rate in myeloid leukemia cells of non-M3 AML patients was 19.7%, significantly higher than control (0.2%) (P0.001). The median concentration of non-M3 CD68 in peripheral blood was 67.97 pg/ml, significantly higher than in control (29.94 pg/ml)（P0.01）. There was no statistically significant difference in the plasma CD68 concentration of the peripheral blood between the newly diagnosed (45.72 pg/ml) and the remission stage (55.12 pg/ml) of non-M3 AML patients by paired analysis (P0.05). The results showed that the higher the expression rate of CD68 in bone marrow, the higher the count of white blood cells in peripheral blood, and the lower the count of hemoglobin and platelet in peripheral blood. The higher the plasma concentration of CD68 in peripheral blood, the higher the white blood cell count and the lower the complete remission rate.The expression of CD68 both in bone marrow and peripheral blood of patients with non-M3 AML is higher than that of control group. Patients with high expression of CD68 show a low rate of complete remission, suggesting that the expression level of CD68 is correlated with treatment response.CD68因子在急性髓系白血病患者中的表达情况及其临床相关性研究.分析急性髓系白血病（AML）患者骨髓及外周血血浆中CD68因子的表达及临床特点.采用四色流式细胞术检测50例初诊AML患者、23例对照组（非血液系统恶性疾病）的骨髓原始细胞CD68的表达情况。采用ELISA法检测85例初诊期、29例缓解期AML患者与24例对照组外周血血浆中CD68的表达情况。分析CD68因子的表达及其与临床特征的相关性.非M3型AML患者骨髓白血病细胞中CD68表达率中位数为19.7%，明显高于对照组的0.2%（P0.001）。非M3型AML患者外周血中CD68浓度中位数为67.97 pg/ml，明显高于对照组的29.94 pg/ml（P0.01）。配对分析非M3型AML患者初诊时（45.72 pg/ml）与缓解期（55.12 pg/ml）外周血血浆中CD68浓度差异无明显统计学意义（P0.05）。分别比较非M3型AML骨髓中CD68的表达率、外周血中CD68浓度与白细胞计数等临床资料相关性的结果表明：骨髓中CD68表达率越高，外周血白细胞数越高，血红蛋白及血小板数越低；外周血血浆中CD68浓度越高，外周血白细胞计数越高，完全缓解率越低.CD68因子在非M3型AML患者骨髓及外周血中的表达均较对照组升高。CD68高表达患者完全缓解率低， CD68表达水平与治疗反应具有相关性.

Background A high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone marrow transplant recipients. However, myeloid sarcoma (MS) after renal transplantation has rarely been reported and the diagnosis is challenging due to its low incidence. Case presentation Here, we report a rare case of a 49-year-old man who developed myeloid sarcoma (MS) in the transplanted kidney two years after renal transplantation. Next-generation sequencing (NGS) showed mutations of KRAS and DNMT3A genes in the MS, and no gene mutations in the bone marrow. He presented a normal karyotype of 46, XY. Following treatment with 6 cycles of systemic chemotherapy, the patient was in satisfactory condition with stable serum creatinine (sCr) levels at the 1-year follow-up. In addition, we performed a detailed review with emphasis on the clinical manifestations, and the diagnostic and therapeutic processes of another 7 patients who developed MS following renal transplantation. Conclusions Our report illustrates the clinical utility of comprehensive genomic profiling in benefiting the diagnosis of MS, the selection of therapeutic strategy and the determination of whether MS is donor-derived.

To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice. According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1). Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P

The metal cations, Al

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Human serum albumin (HSA) is considered as a biomarker for the early diagnosis of renal disease, therefore identifying and detecting HSA in biological fluids (especially urine) with an easy method is of great importance. Herein, we report a novel hydrazide Schiff base fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)pyrazine-2-carbohydrazide (NPC), which self-assembled into nanoparticles in aqueous solution. Based on disassembly-induced emission and the site-specific recognition mechanism, the binding of NPC with HSA resulted in a fluorescence "turn-on" response. Probe NPC exhibited superior selectivity and sensitivity toward HSA with a detection limit of 0.59 mg L-1 in PBS and 0.56 mg L-1 in the urine sample. The site-binding mechanism of NPC with HSA was explored by fluorescence quenching study, Job's plot analysis, HSA destruction, site marker displacement and molecular docking. Fluorescence imaging of HSA in MCF-7 cells was achieved by using a non-toxic NPC probe, suggesting that NPC could be applied to visualize the level of HSA in vivo. More importantly, further practical applications of probe NPC in human urine samples were achieved with satisfactory results by using a fluorometer or test paper, which could provide extensive application in clinical diagnosis.

The discrimination and identification of human serum albumin (HSA) and bovine serum albumin (BSA) is very important, which is due to the vital roles of two SAs in biological and pharmaceutical research. Based on structural screening and docking calculation from a series of homologues, a coumarin Schiff base fluorescent probe 3-hydroxy-N′-((4-oxo-4H-chromen-3-yl)methylene)-2-naphthohydrazide (HCNH) has been designed and synthesized, which could effectively discriminate HSA and BSA. The probe HCNH exhibited superior sensitivity toward HSA and BSA with the detection limits of 10.62 nM and 16.03 nM in PBS solution, respectively. The binding mechanism of HCNH with SAs was studied by Job’s plot analysis, SA destruction and displacement assay. Molecular docking and DFT methods were utilized to provide deep insight into the spatial conformation change of HCNH and binding sites in HSA/BSA. The conformation of HCNH was significantly influenced by the microenvironment provided by HSA and BSA, therefore its fluorescence emission was affected correspondingly. Non-toxic probe HCNH could be successfully used for fluorescence bio-imaging of HSA in cancer cells, which is significantly different from normal cells and favors the application in medical diagnosis.

The metal cations, Al3+ and Mg2+, could affect human health and cell biological processes. Their fast and selective detection using one probe remains a challenge. A novel fluorescence probe, N'-((1-hydroxynaphthalen-2-yl)methylene)isoquinoline-3-carbohydrazide (NHMI), was developed for selectively monitoring Al3+ and Mg2+. The probe NHMI showed a distinctive “turn-on” fluorescence signal towards Al3+ and Mg2+ (cyan for Al3+ with 2556-folds enhancement and yellow for Mg2+ with 88-folds enhancement), which is quite distinct from other metal cations and allows for naked-eye detection. This interesting response was attributed to the influence of PET, ESIPT process and CHEF effect, when Al3+ or Mg2+ chelated with NHMI. Furthermore, the fluorescence titration experiments manifested that the detection limit of probe NHMI for Al3+/Mg2+ was as low as 1.20 × 10–8 M and 7.69 × 10–8 M, respectively. The formed complexes NHMI-Al3+ and NHMI-Mg2+ were analyzed by Job's plot, ESI-MS, 1H NMR and FT-IR. The coordination pockets and fluorescence mechanisms of two metal complexes were explored by density functional theory calculation. Moreover, NHMI showed low cytotoxicity and good cell permeability. Fluorescence bioimaging of Al3+/Mg2+ in MCF-7 cells with NHMI indicated its potential application in biological diagnostic analysis.

A new acylhydrazine-derived Schiff base fluorescence probe DMI based on "ON-OFF-ON" fluorescence strategy was presented in this paper. Probe DMI could detect Cu

A new acylhydrazine-derived Schiff base fluorescence probe DMI based on “ON-OFF-ON” fluorescence strategy was presented in this paper. Probe DMI could detect Cu2+ selectively and sensitively with dramatic fluorescence quenching in CH3OH-PBS (v/v = 3:7) mixed solution. Once the complex DMI-Cu2+ interacted with S2−, 10.67-folds fluorescence increase was induced via a displacement mechanism under the same experimental conditions. The corresponding detection limits for Cu2+ and S2− were calculated to be 1.52 × 10−8 M and 1.79 × 10−8 M, respectively. The structures of DMI and DMI-Cu2+ were systematically characterized by Job's plot analysis, ESI-MS, IR, X-ray diffraction and density functional theory calculations. Furthermore, fluorescence imaging in MCF-7 cells and zebrafish demonstrated the probe DMI could act as a useful tool to monitor and track intracellular Cu2+ and S2−, which was encouraged by remarkable fluorescence performance and low cytotoxicity. Importantly, the complex DMI-Cu2+ could be applied to detect corrupt blood samples, which could estimate the time of death.

Overexpression of tumor biomarker glutathione (GSH) has been documented in numerous types of cancers, therefor GSH-activated light-up chemosensors for tumor identification require great attention. A new colorimetric/fluorescent probe (7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)-4-(dimethylamino) benzohydrazide (HL) was prepared, which could be applied in discriminating Cu2+ and further recognizing GSH based on its Cu complex. Firstly, the probe HL toward Cu2+ exhibited selective fluorescence quenching and obvious color change from yellow to orange-red under visible light. Further, when GSH was introduced to the Cu2+-2HL system, the fluorescence recovered rapidly due to the high affinity of GSH to Cu2+, meanwhile the color reverted back to former yellow. Based on fluorescence titration, the detection limits were calculated as 2.40 × 10−8 M and 1.29 × 10−7 M for Cu2+ and GSH, respectively. The combination mode of HL with Cu2+ was investigated in detail by Job plots, ESI-MS, FT-IR, and DFT studies. Probes HL and Cu2+-2HL showed relatively less toxicity and were employed for biological imaging in cells and zebrafish. Remarkably, the detection for endogenous GSH by this developed sensor platform implied great potential application prospect in cancer diagnosis.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV), which is classified into the genus Phlebovirus and family Phenuiviridae. Reactive plasmacytosis mimicking multiple myeloma is a very rare condition in association with SFTS. Here, we describe two SFTS cases who presented with hyperimmunoglobulinemia, as well as extensive bone marrow and peripheral blood plasmacytosis, which mimicked multiple myeloma (MM). Case presentation We report two cases who presented with fever and blood routine abnormity which were conformed as SFTS eventually. They were performed bone marrow aspiration and were admitted to the department of hematology with a preliminary diagnosis of MM. They all had hyperimmunoglobulinemia, extensive bone marrow and peripheral blood plasma cells, prolonged activated partial thromboplastin time (APTT), elevated hepatic enzyme. The two patients recovered with treatment of doxycycline, human immunoglobulins, plasma transfusion, and other supporting treatments. But case 1 occurred lymphoma 8 months later and died. Conclusion SFTS might be one of differential diagnosis of MM in certain endemic area. We also conclude that SFTSV is a pantropic virus that could injure most tissues and cells of the human body.

The porcine cardiac blood processed Salvia miltiorrhiza (PCB Danshen) is the characteristic processing of Menghe medical school and has been inherited for hundreds of years, commonly used in the treatment of brain ischemia-induced agitation, palpitation and phlegm confusing heart. Ancient and modern physicians believe that porcine cardiac blood is a guiding for heart nourishing drugs, which could enhance the effects of Salvia miltiorrhiza by nourishing and soothing the nerves. However, the material basis and processing mechanism of PCB Danshen are still unclear. This paper investigated the historical evolution and modern research of PCB Danshen, including the clinical application, the intention of clinic processing, the processing technology and recent research of PCB Danshen. In addition, the major problems and significance in research and development of PCB Danshen were further thought and prospected, hoping to provide basic data for material basis and processing mechanism of PCB Danshen, and provide effective support for inheriting and carrying forward the characteristic processing technology of Menghe medical school.

Euphorbia kansui is a Traditional Chinese Medicine widely used for the treatment of oedema, ascites and asthma. However, its serious hepatotoxicity hinders its safe clinical application. The process of stir-baking with vinegar is regularly used to reduce the toxicity of kansui. Up till now, the exact mechanism of the reduction in hepatotoxicity of kansui stir-baked with vinegar has been poorly defined. In this study, decreased contents of five diterpene and one triterpene in kansui (GS-1) after stir-baking with vinegar (GS-2) was investigated by UPLC-QTOF/MS. Flow cytometry and Hoechst staining were used to show that the stir-baking with vinegar process reduces kansui-induced cell apoptosis. Furthermore, the result also indicated that kansui stir-baked with vinegar protects LO2 cells from apoptosis by increasing the cell mitochondrial membrane potential (ΔΨm), decreasing the release of cytochrome c and inhibiting the activities of caspase-9 and caspase-3 as evidenced by means of high content screening (HCS), ELISA and western blotting. These results suggested that the stir-baking vinegar could reduce the hepatotoxicity of kansui by effectively decreasing the contents of toxic terpenoids and inhibiting the intrinsic pathway of hepatocyte cell apoptosis. In conclusion, the study provided significant data for promoting safer and better clinical use of this herb.

Density ρ, refractive index nD, and viscosity η for ionic liquids [Cnmim]Cl (Cnmim = 1-alkyl-3-methylimidazolium; n = 2, 4, 6, 8 for ethyl, butyl, hetyl, and octyl) + N,N-dimethylformamide (DMF) binary systems have been investigated at atmospheric pressure from 288.15 K to 318.15 K. The molar excess Gibbs energy ΔG*E, volumetric properties including excess molar volume VE, and apparent molar volume Vφ,i have been calculated from the experimental data. Furthermore, the refractive index and viscosity deviations (ΔnD, Δη) from the ideal behavior have been obtained and well fitted to the Redlich–Kister equation. Our results show that DMF can effectively adjust the physicochemical properties of 1-alkyl-3-methylimidazolium ionic liquids.

Newborn screening in urine is important for the diagnosis of many inborn errors of metabolism (IEM). Capillary electrophoresis with laser-induced fluorescence detection (CE–LIF) is a major technological advance in screening IEM. It has the advantage of sensitive and simultaneous multiple disease screening with minimal sample requirement. The analytes were derivatized with fluorescein isothiocyanate (FITC) prior to CE–LIF analysis. In urine samples, free amino acids (AAs) were well separated from other coexisting components, exhibiting a linear calibration over the concentration range 0.01–5.0 μmol/L with the limits of detection (LODs) ranging from 0.005 to 0.010 μmol/L. The relative standard deviations (RSDs) were in the range 0.1–1.0% for peak area, and 0.2–1.0% for migration time, respectively. Under optimized conditions, the method presented here has been successfully used for the simultaneous and sensitive analysis of seven AAs in urine samples of newborn babies, and evaluating the effect of therapy as well.

The dried roots of Euphorbia kansui (kansui) have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by 1H, 13C NMR spectroscopy and ESI-MS as kansuinine A (1), kansuinine B (2), kansuinine C (3), kansuiphorin C (4), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5), 3-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (6), 3-O-(2'E,4'Z-decadienoyl)-20-deoxyingenol (7), 3-O-benzoyl-20-deoxyingenol (8), 5-O-benzoyl-20-deoxyingenol (9), kansenone (10), epi-kansenone (11), euphol (12). All these 12 terpernoids were evaluated in vitro for cytotoxicity on L-O2 and GES-1 cell lines. Most ingenane-type diterpenoids and 8-ene-7-one triterpenoids (5–11) exhibited a relatively lower IC50 value; therefore, these compounds had stronger cytotoxicity against human normal cell lines L-O2 and GES-1 with dose-dependent relationships. These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.

Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8), inverted phase contrast microscope and flow cytometry were used to demonstrate that lingenol significantly inhibited L-O2 cells proliferation, and induced cell cycle arrest and apoptosis. Moreover, the results investigated that lingenol markedly disrupted mitochondrial functions by high content screening (HCS). In addition, the up-regulation of cytochrome c, AIF and Apaf-1 and activation of caspases were found in L-O2 cells detected by Western blotting and ELISA assay, which was required for lingenol activation of cytochrome c-mediated caspase cascades and AIF-mediated DNA damage. Mechanistic investigations revealed that lingenol significantly down-regulated the Bcl-2/Bax ratio and enhanced the reactive oxygen species (ROS) in L-O2 cells. These data collectively indicated that lingenol modulation of ROS and Bcl-2/Bax ratio led to cell cycle arrest and mitochondrial-mediated apoptosis in L-O2 cells in vitro. All of these results will be helpful to reveal the hepatotoxicity mechanism of Euphorbia kansui and to effectively guide safer and better clinical application of this herb.

Combretastatin A-4, first isolated from the African willow tree Combretum caffrum, is a tubulin polymerization inhibitor in medicine. It was first postulated as a potential fungicide targeting fungal tubulin for plant disease control in this study. Combretastatin A-4 and its derivatives were synthesized and tested against Rhizoctonia solani and Pyricularia oryzae. Several compounds have EC50 values similar to or better than that of isoprothiolane, which is widely used for rice disease control. Structure-activity relationship study indicated the the cis configuration and hydroxyl group in combretastatin A-4 are crucial to the antifungal effect. Molecular modeling indicated the binding sites of combretastatin A-4 and carbendazim on fungal tubulin are totally different. The bioactivity of combretastatin A-4 and its derivatives against carbendazim-resistant strains was demonstrated in this study. The results provide a new approach for fungicide discovery and fungicide resistance management.

To explore the expression of insulin-like growth factor binding protein 3 (IGFBP3) in acute myeloid leukemia and its clinical significance.Using GAPDH as internal reference, IGFBP3 gene expression was detected in the bone marrow mononuclear cells of 43 de novo AML patients, 36 patients with complete remission (CR) and 28 cases of controls by using SYBR-Green I real-time quantitative PCR, the differences of gene expression between the three groups were compared.IGFBP3 gene expression level in the de novo group were lower than that in CR group and control group (P0.05), but there was no statistically significant difference of IGFBP3 expression level in CR group and control group (P0.05).The IGFBP3 as a tumor suppressor gene may play a role in the pathogenesis of acute myeloid leukemia, its expression level is recovered after complete remission, therefore, IGFBP3 can be used as an indicator of evaluating clinical curative effect.

This study aims to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 using the orthogonal design method, and to investigate its effects of the component formula on cell proliferation, apoptosis and cytoskeleton in lung cancer A549 cells. The orthogonal design method was introduced to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 cells. CCK-8 assay and Real-time cell analysis were adapted to analyze the effect of component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on A549 cells viability at different time and dose. Cell apoptosis was measured by Annexin V- FITC/PI double staining and flow cytometry. Cell skeleton protein F-actin was detected by high content screening (HCS). The optimizing component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma for total salvianolic acid, total saponins of panax ginseng and ginseng polysaccharide doses were 5, 10, 5 mg L(-1). CCK-8 assay and real-time cell analysis demonstrated that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma treatment could significantly decrease the A549 cell viability in both dose- and time-dependent manner compared with control group (P0.01). Moreover, the increase of cell apoptosis was detected by Annexin V-FITC/PI double staining and flow cytometry when cells treated with the component formula, which indicating that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma could induce A549 cell apoptosis in a time-dependent manner compared with control group (P0.01). Furthermore, compared with control group, a significant decrease in A549 cell skeleton area was found in the component formula-exposed cells in the dose-dependent manner (P0.01). In summary, the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma inhibits A549 cell proliferation by inducing cell apoptosis and decreasing cell microfilament formation. All of these results will be helpful to reveal antitumor mechanism of the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma, which provides a basis for the exploration of antitumor mechanism of the component formula on lung cancer.

To compare the difference of Euphorbia Pekinensis Radix before and after being processed with vinegar in the toxicity on rat small intestinal crypt epithelial cells IEC-6, and make a preliminary study on the mechanism of detoxication of Euphorbia Pekinensis Radix processed with vinegar.With rat small intestinal crypt epithelial cells IEC-6 as the study object, the MTT method was adopted to detect the effect of Euphorbia Pekinensis Radix before and after being processed with vinegar on IEC-6 cell activity. The morphology of cells were observed by the inverted microscope. The down-regulated mitochondrial apoptosis pathway of enterocytes caused by the vinegar processing was analyzed by using the high content screening.Compared with the negative control group, the proliferation inhibition experiment showed that Euphorbia Pekinensis Radix showed a relatively high intestinal cell toxicity (P0.01). The results of HCS analysis showed that Euphorbia Pekinensis Radix could significantly reduce the cell nucleus Hoechst fluorescence intensity and mitochondria membrane (P0.05, P0.01), and increase Annexin V-FITC and PI fluorescence intensity and membrane permeability (P0.01, P0.01, P0.01). After being processed with vinegar, compared with Euphorbia Pekinensis Radix groups with different doses, Euphorbia Pekinensis Radix processed with vinegar could significantly decrease the cell proliferation inhibition effect on enterocytes, increase the cell nuclear Hoechst fluorescence intensity and mitochondria membrane (P0.05, P0.05), and decrease Annexin V-FITC and PI fluorescence intensity and membrane permeability (P0.01, P0.01, P0.05), and showed a certain dose-effect relationship.The vinegar processing can further reduce the toxicity of Euphorbia Pekinensis Radix on enterocytes. Its possible mechanism can decrease the effect of Euphorbia Pekinensis Radix on the permeability of IEC-6 cell membrane, so as to provide a basis for further explanation of the detoxication mechanism of Euphorbia Pekinensis Radix processed with vinegar.

Endoplasmic reticulum stress (ERS) is a new pathway inducing cell apoptosis that has been discovered in recent years. This study focused on the protective effect of Liangxue Huayu recipe (LHR) on tumor necrosis factor-alpha (TNF-alpha) and D-GalN-induced hepatocyte apoptosis. It found that TNF-alpha and D-GalN could obviously inhibit hepatocyte proliferation, induce cell apoptosis, and significantly increase free calcium ions in cytoplasms, as well as protein expressions of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. After the administration of LHR of different concentrations, compared with the TNF-alpha/GalN injury group, LHR could significantly alleviated L02 hepatocyte proliferation, decreased cell apoptosis, inhibited growth of intracytoplasmic free calcium content, and gradually reduced the protein expressions of phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. These findings indicated that LHR has the inhibitory effect on TNF-alpha and D-GalN-induced hepatocyte apoptosis. Its mechanism may be related to down-regulation of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP that maintain calcium homeostasis in endoplasmic reticulum.

To study the mechanism of the reducing mechanism of hepatotoxicity induced by ethyl acetate fractions of Kansui Radix stir-baked with vinegar in mice.Mice with normal ICR were orally administered with ethyl acetate fractions of Kansui Radix and Kansui Radix stir-baked with vinegar. Their blood and liver homogenate were collected to detect the level of AST, ALT, LDH, SOD, activities of Na(+) -K(+) -ATPase and Ca(2+) -Mg(2+) -ATPase, GSH and MDA. Liver tissues were collected for HE staining and morphological observation under light microscope.According to the results of pathological sections, compared with the control group, all of Kansui groups showed a significant increase in the hepatic tissues injury (P0.01). Compared with Kansui groups, all of vinegar-baked groups showed a significant decrease in the hepatic tissues injury (P0.01). Compared with the control group, all of Kansui groups showed a significant increase in ALT, AST and LDH (P0.05, P0.001) in serum and hepatic tissues, and significantly decrease in the activity of SOD (P0.001) and the content of GSH. They also showed a significant increase in MDA (P0.001) and a significant decrease in the level of Na(+) -K(+) -ATPase and Ca(2+) -Mg(2+) -ATPase (P0.01) in hepatic tissues, with a certain dose-effect relationship. Compared with all of Kansui groups, all of vinegar-baked groups showed a significant decrease in ALT, AST and LDH (P0.05, P0.001), and a notable increase in SOD (P0.001) and GSH in serum and hepatic tissues. They also showed a remarkable decrease in MDA (P0.001), and a significant increase in the level of Na(+) -K(+) -ATPase and Ca(2+) - Mg(2+) -ATPase (P0.01) in hepatic tissues, with a certain dose-effect relationship.Being stir-baked with vinegar can significantly reduce the hepatotoxicity of Kansui Radix. Its mechanism may be related to the reduction of the effect of Kansui Radix on the permeability of hepatic tissues cell membranes and the oxidative injury.

To compare the toxicity of Euphorbia pekinensis before and after being processed by vinegar on normal liver cells LO2, and discuss its possible mechanism.LO2 cells were cultured in vitro, and processed with different concentrations of crude and vinegar-processed E. pekinensis. MTT assay was used to measure the inhibitory effect of LO2 cell; Hoechst 33258 staining was used to observe the morphological changes in apoptosis cell; Annexin V-FITC flow cytometry was used to analyze the apoptotic rate of LO2 cell; PI staining flow cytometry was used to analyze its impact on cell cycle. The level or content of ALT, AST, LDH, SOD, MDA and GSH were observed as well.Compared with the negative control group, crude E. pekinensis at all concentrations could obviously inhibit LO2 cell proliferation, induce LO2 cell apoptosis and cause cell arrest in S phase, with significant differences (P0.05). E. pekinensis could significantly increase the levels of ALT, AST and LDH (P0.05) in the supernatant of cell culture fluid, significantly decrease the level of SOD and the content of GSH (P0.05) , and significantly increase the content of MDA (P0.05). Compared with the crude E. pekinensis group, E. pekinensis after being vinegar-processed can significantly reduce cell apoptotic rate, cell cycle arrest, activities of ALT, AST, LDH in the supernatant of cell culture fluid (P0.05) , and remarkably increase the level of SOD and the content of GSH, but reduce the content of MDA in the supernatant of cell culture fluid.Vinegar-processed E. pekinensis can release the cytotoxicity of LO2 cell. Its mechanism may be related to the decrease in the oxidative damage of LO2 cells, thereby reducing the cell cycle arrest and apoptosis.