【Objective】 To explore the effects and the possible mechanism of RNA targeting membrane-bound prostaglandin E2 synthase l（mPGES- 1）on proliferation，apoptosis and drug resistance of leukemia cell line K562/A.【Methods】RNA interference was used to inhibit the expression of mPGES-1 of K562/A cells. Four groups were set up as follows：untreated group（K562/A），negative control group after interference（K562/A-NC），group after interference（K562/ A-KD），and group after interference with exogenous PGE2（K562/A-KD+PGE2）.Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry. Concentration of PGE2 was detected by ELISA. Proteins expression was detected by western blot.【Results】The expression of mPGES- 1 in K562/A cells was significantly down- regulated and the synthesis of PGE2 decreased（P < 0.000 1）after RNA interference. After RNA interference，the proliferation of K562/A cells was inhibited and apoptosis increased，and the sensitivity to chemotherapy drugs was enhanced（P < 0.05）. Meanwhile，the expression of β-catenin and MDR1 was decreased（P < 0.01）. Exogenous PGE2 could reverse the effect of RNA interference on proliferation ，apoptosis and drug sensitivity in K562/A cells（P < 0.05），and up-regulate the expression of β-catenin and MDR1（P < 0.01）. XAV939，an inhibitor of β-catenin，could down-regulate the expression of β- catenin and MDR1 in an dose- dependent pattern in K562/A cells（P < 0.05）.【Conclusions】RNA interference of mPGES- 1 could inhibit proliferation，induce apoptosis and reverse drug resistance in K562/A cells. The mechanism was related to reducing the synthesis of PGE2 and thus down- regulating the expression of β- catenin and MDR1. Wnt/β- catenin signal pathway may participate in the regulation of MDR1 by mPGES-1/PGE2.

【Objective】To explore the effects and the possible mechanism of KPT- 8602，a novel selective inhibitor of nuclear export protein （XPO1），on proliferation，cell cycle and apoptosis in human histiocytic lymphoma cell line U937 cells.【Methods】U937 cells were treated with different concentrations of KPT- 8602. Cell viability was assessed by CCK-8 assay. The cell cycle distribution and the apoptosis rate were analyzed by flow cytometry. The proteins expression of XPO1，p-AKT，AKT，Cleaved Caspase-3，p21 were determined by Western blot. Fluorescence microscope was used in observing the intracellular location of XPO1. 【Results】 KPT- 8602 inhibited the growth of U937 cells in a dose- dependent（P<0.001）and time- dependent manner（P<0.001），but normal PBMC were unaffected. 48 h after treatment with KPT-8602，a higher proportion of cells in G1 phase was observed（P<0.001）and the apoptosis rate increased（P=0.016）with drug concentration in U937 cells. XPO1 protein expression of U937 cells was significantly higher than normal PBMC（P=0.003）. 48 h after treatment with KPT- 8602，the protein expression of XPO1 decreased（P=0.011），p-AKT decreased（P=0.011），and Cleaved Caspase- 3 increased（P=0.009）. In addition，the protein expression of p21，the cargo protein of XPO1，increased in both the nuclei and the cytoplasm（P<0.05）after treatment with KPT- 8602. XPO1 decreased in both the nuclei and the cytoplasm under the fluorescence microscope after treatment with KPT- 8602.【Conclusion】KPT- 8602 can inhibit the proliferation of U937 cells，block the cell cycle at G1 phase，and induce cell apoptosis，which may partially be attributed to the down-regulation of XPO1 and inhibition of PI3K/AKT signaling.

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.
China ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs

Objective To investigate the therapeutic effect of mechanical loading on obesity and non-alcoholic fatty liver disease. Methods Thirty 6-week-old female C57BL/6 mice (body weight 18 g) were randomly assigned into three groups: normal control group (NC group, n=10), high-fat diet group (HF group, n=10) and high-fat diet with mechanical loading treatment group (HF+L group, n=10). All mice except for NC group were fed with high-fat diet for 12 weeks. After 6 weeks of high-fat diet, mice of HF+L group received 6-week mechanical loading. The whole body composition was analyzed to detect the total body fat content. The mesenteric fat, perirenal fat, inguinal fat, periuterine fat and the liver were collected and weighed. A portion of the liver sample was isolated for histological analysis (Oil red O staining and HE staining) to observe pathologic changes, while the other was used for Western blot assay to detect the expression of eIF2α, p-eIF2α and ATF4, which were the marker proteins of endoplasmic reticulum stress. Results Compared with the NC group, high-fat diet resulted in a significant increase in body weight and body fat (P＜0.05). After mechanical loading treatment, the body weight and body fat were significantly decreased in the HF+L group compared with those of HF group (P＜0.05). Hepatic histological analysis showed that high-fat diet induced hepatic steatosis, which was effectively alleviated by mechanical loading treatment (P＜0.05). Western blot analysis indicated that high-fat diet led to higher expression levels of p-eIF2α and ATF4 in liver, and mechanical loading was effective in inhibiting the increased expressions of p-eIF2α and ATF4. Conclusion Mechanical loading can effectively alleviate obesity and non-alcoholic fatty liver disease caused by high-fat diet, and its effects may be associated with endoplasmic reticulum stress in liver.

[Objective]Examine the expression of microsomal prostaglandin E synthase-1(mPGES-1)and nuclear transcription factor kappa B p65(NF-κB p65)in diffuse large B cell lymphoma(DLBCL),assessing their correlation with clinical variables,prognosis and potential clinical valve.[Methods]The immunohistochemistry was uesd to investigate the expression of mPGES-1 and NF-κB p65 in 83 DLBCL patiens'tissues.The relationship between these two proteins and the clinical variables and prognosis of these patients was evaluated.[Results]The high expression of mPGES-1 and NF-κB p65 were observed in 65.1%(54/83)and 73.5%(61/83)cases of DLBCL,respectively.The expression level of NF-κB p65 was positively correlated with mPGES-1 expression(P<0.05).The expression of these two proteins was found to be significantly associated with B cell lymphoma/leukemia-2 protein(BCL-2),higher expression of Ki67,higher lactate dehydrogenase (LDH),more extranodal lesions,advanced Ann Arbor stage and higher international prognostic index(IPI)score(P<0.05). In addition,NF-κB p65 was related with multiple myeloma oncogene 1(MUM1),pathological type(P<0.05). Both mPGES-1 and NF-κB p65 overexpression was correlated with worse overall survival(OS)while NF-κB p65 was an in-dependent prognostic factor for OS of DLBCL(P<0.05).[Conclusions]mPGES-1 and NF-κB p65 were highly expressed in DLBCL and closely linked with each other. The overexpression of mPGES-1 and NF-κB p65 was correlated with tumor progression and unfavorable prognosis in patients with DLBCL.

BACKGROUNDPatients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.

METHODSParticipants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.

RESULTSIn total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis.

CONCLUSIONSHemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Adult ; Aged ; China ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Renal Dialysis ; adverse effects ; mortality ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the effects of shRNA targeting mPGES-1 on tumorigenicity of human acute leukemia K562 cells in nude mice in vivo and its mechanisms.

METHODSFor experiment 3 groups including KD group(expression of mPGES-1 in K562 cells was down-regulated by shRNA), CON (cells without any treatment) and NC group (cells treated with nonspecific-sequence shRNA) were set-up. Western blot was used to test the expression of β-catenin and cyclinD1 in cells. Then the cells of 3 groups were implanted into BALB/c nude mice subcutaneously to establish murine xenograft model. The growth state of the mice and the size of the xenograft tumor were recorded. HE staining was used to observe the morphology of xenograft tumor. Expressions of β-catenin and cyclinD1 in xenograft tumor were detected by immunohistochemical staining.

RESULTSIn vitro the expression of β-catenin and cyclinD1 in KD group were lower than the CON group and NC group (P<0.05). In vivo the tumor volume and weight of KD group were significant smaller than the other two groups (P<0.01). HE staining showed that tissues in the KD group were relatively looser in arrangement with smaller cell nucleus and less cytoplasm. The expression of β-catenin and cyclinD1 in the KD group were remarkable weak as compared with that in CON group and NC group (P<0.05).

CONCLUSIONDown-regulating the expression of mPGES-1 by shRNA may significantly inhibit the tumorigenicity of K562 cells in nude mice in vivo and its mechanism may be related with the inhibition of expression of β-catenin and cyclinD1.

OBJECTIVETo investigate the clinical significance of bone marrow morphological differences in the differential diagnosis of megaloblastic anemia (MM) and refractory anemia (R4).

METHODSA total of 60 anemia patients selected from our hospital between April 2004 and April 2015 were divided into MA group (30 cases) and RA group (30 cases) in accordance with their clinical diagnosis. Clinical manifestations, results of bone marrow morphology test, blood examination, peripheral blood smear, erythroid megaloblastic variability rate and nucleated red blood cell level in the 2 groups were compared and analyzed.

RESULTSIncidence of fever, hemorrhage, digestive reaction, splenomegaly and fatigue as well as hemoglobin level, platelets and white blood cell counts in patients of MA group were similar to those of RA group, there was no statistically significant difference between 2 groups (P>0.05). The percentages of dysplastic hematopoiesis in erythroid cells, granulocytic cells, magakaryoajtic cells, the PAS-positive rate and red blood cell distribution in the MA patients were obviously lower than those in the RA patients, while the erythroid megaloblastic variability rate (90%) in MA group was obviously higher than that in RA patients (10%) and with statistically significant difference (P<0.05). The percentage of immature red blood cells was similar between MA group (53.33%) and RA group (60.00%), without significant difference (P>0.05).

CONCLUSIONMost of clinical manifestations and peripheral blood smear results are consistent in MA patients and RA patients, bone marrow morphology detection in RA group should be focused on lymphocytoid micromegakaryocytes, while the erythroid megaloblastic cell body is the focus in MA group, PAS can be used as a diagnostic criteria.

Anemia, Megaloblastic ; diagnosis ; Anemia, Refractory ; diagnosis ; Bone Marrow ; pathology ; Diagnosis, Differential ; Erythrocyte Count ; Humans ; Leukocyte Count ; Megakaryocytes ; cytology

Chinese materia medica resource (CMM resource) is the foundation of the development of traditional Chinese medicine. In the study of sustainable utilization of CMM resource, adopting innovative theory and method to find new CMM resource is one of hotspots and always highlighted. Pharmacophylogeny interrogates the phylogenetic relationship of medicinal organisms (especially medicinal plants), as well as the intrinsic correlation of morphological taxonomy, molecular phylogeny, chemical constituents, and therapeutic efficacy (ethnopharmacology and pharmacological activity). This new discipline may have the power to change the way we utilize medicinal plant resources and develop plant-based drugs. Phylogenomics is the crossing of evolutionary biology and genomics, in which genome data are utilized for evolutionary reconstructions. Phylogenomics can be integrated into the flow chart of drug discovery and development, and extends the field of pharmacophylogeny at the omic level, thus the concept of pharmacophylogenomics could be redefined in the context of plant pharmaceutical resources. This contribution gives a brief discourse of knowledge pedigree of pharmacophylogeny, epistemology and paradigm shift, highlighting the theoretical and practical values of pharmacophylogenomics. Many medicinally important tribes and genera, such as Clematis, Pulsatilla, Anemone, Cimicifugeae, Nigella, Delphinieae, Adonideae, Aquilegia, Thalictrum, and Coptis, belong to Ranunculaceae family. Compared to other plant families, Ranunculaceae has the most species that are recorded in China Pharmacopoeia (CP) 2010. However, many Ranunculaceae species, e. g., those that are closely related to CP species, as well as those endemic to China, have not been investigated in depth, and their phylogenetic relationship and potential in medicinal use remain elusive. As such, it is proposed to select Ranunculaceae to exemplify the utility of pharmacophylogenomics and to elaborate the new concept empirically. It is argued that phylogenetic and evolutionary relationship of medicinally important tribes and genera within Ranunculaceae could be elucidated at the genomic, transcriptomic, and metabolomic levels, from which the intrinsic correlation between medicinal plant genotype and metabolic phenotype, and between genetic diversity and chemodivesity of closely related taxa, could be revealed. This proof-of-concept study regards pharmacophylogenomics as the updated version of pharmacophylogeny and would enrich the intension and spread the extension of pharmacophylogeny. The interdisciplinary knowledge and techniques will be integrated in the proposed study to promote development of CMM resource discipline and to boost sustainable development of Chinese medicinal plant resources.
China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Knowledge ; Medicine, Chinese Traditional ; Phylogeny ; Plants, Medicinal ; chemistry ; classification ; genetics