With the deepening of research in recent years, tumor metabolic reprogramming has gradually become the focus of research, and targeting tumor cell metabolism has also become a new means of tumor therapy. The metabolic process affects almost all the physiological processes of the organism, and lipid metabolism is an important part of the metabolic process. Studies have shown that changes in lipid uptake, storage and fatty acid synthesis and decomposition have occurred in a variety of tumors. Abnormal lipid metabolism will promote the rapid proliferation of tumors. Abnormal expression of a variety of key metabolic enzymes in the process of lipid metabolism is the key to tumor progression. The purpose of this paper is to explain the metabolic regulation of lipid metabolism and related metabolic enzymes in hematological tumors, and to provide ideas for the treatment of hematological tumors.

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC₅₀) was 13.8 μmol·L^-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC₅₀: 41.99 μmol·L^-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

OBJECTIVETo evaluate the clinical effectiveness of Yiqi Huoxue Tongyang Xiezhuo Recipe (YHTXR, capable of supplementing qi, activating blood, warming yang, and discharge turbidity) in treating coronary atherosclerotic heart disease (CAHD). and chronic heart failure (CHF) with carotid plaque patients, and to explore new ways of Chinese medicine (CM).

METHODSTotally 69 CAHD-CHF patients of qi deficiency phlegm stasis syndrome (QDPSS) with carotid plaque were recruited in this study using parallel cohort method. They were assigned to the treatment group (35 cases) and the control group (34 cases). Patients in the control group received routine treatment of Western medicine, while those in the treatment group were additionally treated with YHTXR (twice daily). The therapeutic course for all was three months. Cardiac function levels, echocardiography, carotid plaque, blood lipids and safety indicators were observed before and after treatment.

RESULTSAfter treatment the improvement of cardiac function levels was better in the treatment group than in the control group (P < 0.05). Decreased LDL-C levels were higher in the treatment group than in the control group (P < 0.01). There was statistical difference in left ventricular ejection fraction (LVEF), carotid intima-media thickness (IMT), LDL-C, TC, TG in the treatment group between before and after treatment (P < 0.05). LDL-C and TG also decreased in the control group after treatment (P <0.05). There was no significant difference in the left ventricular ejection fraction, carotid IMT, or TC in the control group between before and after treatment (P > 0.05). There was no significant difference in stroke volume, left ventricular end-diastolic diameter, the area of carotid artery plaque, or HDL-C in the two groups between before and after treatment (P > 0.05).

CONCLUSIONSYHTXR could effectively improve cardiac functions of CAHD-CHF patients of QDPSS with carotid plaque, reduce blood lipids and IMT. It had no significant adverse reactions for elderly patients in short term.

Carotid Intima-Media Thickness ; Coronary Disease ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart ; Heart Failure ; drug therapy ; Humans ; Lipids ; Plaque, Atherosclerotic ; drug therapy ; Qi ; Ventricular Function, Left

AIM: To investigate therapeutic efficiency of amniotic extraction on dry eye in rabbit model induced by topical benzalkonium chloride (BAC).
METHODS: Totally 26 rabbits (26 right eyes) with dry eye model were studied and divided into two groups:group A (control group with PBS eye drops, n = 13) and group B ( amniotic extraction group, n = 13). Another two rabbits were chosen as normal control. The SchirmerⅠ tests ( S Ⅰ t) and corneal fluorescein staining ( FL) were made, and the tear total protein content, amylase activity, lactoferrin, lysozyme contents, goblet cell density were performed in two groups before treatment and 1, 2, 4 and 8 wk after treatment.
RESULTS: There were significant differences in SIT, FL scores, lysozyme activity and goblet cell density among different groups at different time points (P<0. 05). But, there was no significant differences in SⅠt, FL scores, lysozyme activity and goblet cell density between two groups before treatment (P>0. 05). After 8wks' treatment with PBS, the mean differences of the group A showed great changes in SⅠt, lysozyme and goblet cell density compared with those before treatment ( P < 0. 05); but there was no significant differences in FL scores compared with those before treatment (P>0. 05). As for group B, 8wks after treatment, there were statistical changes in SⅠt, FL, lysozyme (P<0. 05); but there was no significant differences in goblet cell density compared with those before treatment ( P > 0. 05). It was evident that statistical differences were observed in S Ⅰ t, FL scores, lysozyme activity and goblet cell density between two groups at each time point (P<0. 05). However, there were no significant differences in total protein, lactoferrin, amylase activity at different time points (P>0. 05). Meanwhile there was no significant differences in total protein, lactoferrin, amylase activity between two groups before treatment ( P > 0. 05 ). But there were significant differences in total protein, lactoferrin, amylase activity between two groups after 4 and 8 wks'treatment (P<0. 05).
CONCLUSION: Amniotic extraction has significant therapeutic effect on the dry eye in rabbit model.

Objective To investigate the effects of uncoupling protein 2 (UCP2) on the myocardial cells of mice with type 2 diabetes mellitus combined with hyperuricemia (HUA), and clarify the mechanism thereof. Methods The mouse cardiac myocytes (MCM) cultured with 25mmol/L high glucose (HG) medium were divided into two groups: HG plus 300μmol/L sodium palmitate for 18 hours as high glucose and high fat (HG+HF) group, and HG+HF plus 1500μmol/L uric acid (UA) for 18 hours as HG+HF+HUA group. Then the myocardial cells in HG+HF+HUA group, by use or not use UCP2 inhibitor genipin, were further divided into two groups: vehicle group and genipin group. In order to verify the mechanism of UCP2 in myocardial cells injury caused by high glucose, high lipid and high uric acid, the myocardial cells were divided again into genipin group and genipin+N-acetylcysteine (NAC) group. Accordingly, the apoptosis of myocardial cells were measured by flow cytometry at specific time, the mRNA and protein expressions of UCP2 were determined by q-PCR and Western blotting, and the levels of reactive oxygen species (ROS) were detected by DHE staining and ELISA. Results The apoptosis rate of myocardial cells increased obviously, and the expression levels of UCP2 decreased and of ROS elevated significantly in HG+HF+HUA group than in HG+HF group (P<0.05). As the expression levels of UCP2 decreased by genipin intervention, the apoptosis rate of myocardial cells and ROS level in HG+HF+HUA group increased more obviously (P<0.05). In contrast, such an effect was reversed by the application of antioxidants NAC (P<0.05). Conclusion UCP2 can inhibit oxidative stress and alleviate the apoptosis of myocardial cells induced by high glucose, high fat and high uric acid.

OBJECTIVETo discuss the application of multiple seasonal autoregressive integrated moving average (ARIMA) predictive model of time series and to establish a predictive incidence model of tuberculosis.

METHODSParameters of the model were estimated using conditional least squares method according to the data of tuberculosis incidence and the averaged population in a district in Chongqing from 1993 to 2004. In a structure determined according to criteria of residual un-correlation and conclusion, ARIMA predictive model was established and the order of model was confirmed by Akaike's Information Criterion (AIC, for short) and Schwartz's Bayesian Information Criterion (SBC or BIC, for short).

RESULTSThere were significant differences of the fitted multiple seasonal moving-average coefficients with the nonseasonal and the seasonal moving-average coefficients being 0.84076 and 0.46602 respectively. The estimated variance was 0.088589, AIC = 19.75979, SBC = 23.28219. Autocorrelation check of residuals of model was white-noise residual. ARIMA(0,1,1)(0,1,1)4NOINT seemed to be the most appropriate model by chi2 test.

CONCLUSIONThe multiple seasonal ARIMA model can be used to forecast for tuberculosis incidence with high prediction and precision in a short-term.

China ; epidemiology ; Humans ; Incidence ; Models, Statistical ; Tuberculosis ; epidemiology ; prevention & control ; Weather

A quick HPLC-ESI-MS/MS method was established for simultaneous determination of three chemical compositions in Usnea, including usnic acid, diffractaic acid, and ramalic acid. The separation was performed on a chromatographic column of Agilent ZORBAX SB-C, (4.6 mm x 250 mm, 5 µm), and the mobile phase was methanol (0.05% formic acid)-0.05% formic acid solution (4 mmol ammonium acetate), with an isocratic elution at a flow rate of 0.8 ml · min⁻¹. Multiple reaction monitoring scanning mode (MRM) was performed combined with the ion switching technology in positive and negative ion switching mode to apply for the quantitative determination. The calibration curves for the above three compounds were linear in corresponding injection amount. Their average recoveries were 95.0%-105.1%, with RSDs of 1.1%-5.2%. The method was simple, rapid, accurate with high repeatability, which could provide a reference for overcalling evaluation the quality of Usnea.
Chromatography, High Pressure Liquid ; methods ; Hydroxybenzoates ; analysis ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods ; Usnea ; chemistry

Aptamers are single-stranded oligonucleotides ( DNA or RNA ) selected through a technology termed "Systematic evolution of ligands by exponential enrichment" ( SELEX ) . In addition to high affinity and high specificity for their target molecules, aptamers have some advantages such as low molecular weight, easy synthesis, high chemical stability, low immunogenicity, and convenient modification. Based on the Cell-SELEX technique, a panel of aptamers which can specifically recognize target cell lines has been generated. By targeting specific membrane proteins in their native state, these aptamers can identify subtle molecular differences among different cell lines, thus have attracted a broad interest in biomedical research. In this review, we summarized the development of aptamers and their use in detection, profiling and imaging of tumor cells. Also, their perspectives were discussed.

Aim To investigate the effect of ginsen-oside metabolite compound K ( CK) on migration and invasion of human hepatocellular carcinoma line HepG2, and the possible signaling pathway underlying these processes .Methods HepG2 cells were exposed to ginsenoside CK (0, 10, 20, 40, 80 μmol· L-1 ) for 24 h.The cell viability was examined by MTT as-say, and the ability of migration and invasion was ob-served with the wound healing and transwell assay .The expression of E-cadherin , N-cadherin and other related signal molecules such as p-ERK, ERK, p-Akt, Akt were detected by Western blot .Results The cell via-bility was significantly reduced by ginsenoside CK (20, 40, 80 μmol· L-1) (P<0.01).The ability of cell migration and invasion was significantly inhibited after exposure to ginsenoside CK .After treatment with ginsenoside CK (20, 40, 80 μmol · L-1 ) in HepG2 cells, the expression of E-cadherin markedly in-creased, while N-cadherin expression significantly de-creased.Meanwhile, the expression of p-ERK and p-Akt decreased after treated with ginsenoside CK .Con-clusion Ginsenoside CK inhibits the migration and invasion of human hepatocellular carcinoma line HepG2, which may be through suppression of ERK and Akt signaling .