Circulating tumor DNAs (ctDNAs) are DNA fragments released from tumor cells into bloodstream, containing genetic mutations and epigenetic variations related to cancer. DNA methylation variation is a kind of epigenetic variation which happens in early carcinogenesis and dynamically changes with cancer development. Liquid biopsy of ctDNA methylation has the advantages of non-invasiveness, target molecule stableness, considerable cost-effectiveness, high diagnostic performance and wide application expansion, detection of whose level is conducive to early diagnosis and prognostic evaluation of cancer. The pre-analytical procedures and methylation detection methodologies significantly influence after test results, and should be standardized to obtain high quality results. Up to now, a large amount of literature covering the utility of ctDNA methylation in cancer diagnosis and prognosis have been published. It is believed that in the near future, the detection process of ctDNA methylation would be standardized, and the large-scale clinical application of ctDNA methylation as a liquid biopsy project would be promoted.

OBJECTIVE To investigate the protective effect of total saponins from stems and leaves of Panax ginseng (GSLS) on cisplatin (CDDP)-induced kidney damage in mice and its possible mechanism. METHODS Thirty-two male ICR mice were randomly divided into normal control group, CDDP group, and GSLS(150 and 300)+CDDP groups. GSLS was administered to mice by oral gavage once a day for 7 d. On the 7th day, a single injection of CDDP 20 mg·kg-1 was given 1 h after GSLS 150 and 300 mg·kg-1 before GSLS 150 and 300 mg·kg-1 continued to be given for 3 d. Blood urea nitrogen (BUN) and creatinine (CRE) , catalase (CAT) in renal tissue, reduced glutathione (GSH), tumor necrosis factorα(TNF-α) and interleukin 1β(IL-1β) of cisplatin induced mice were detected after 72 h. HE and PAS staining were used to observe the renal histopathological changes;While TUNEL and Hoechst33258 staining were employed to observe apoptosis in kidney tissues. RESULTS Compared with normal control group, CDDP group had a significant reduction in relative body mass (P<0.05), and the level of GSH and CAT in kidney tissues (P<0.05). The level of CRE, BUN, TNF-α, and IL-1βin serum and renal indexes significantly increased (P<0.05, P<0.01), especially BUN and CRE that respectively doubled and quadrupled. CDDP group developed glomerulus swelling, renal tubular expansion and epithelial cell necrosis. Trans?parent tube type of tube cavity appeared, the nucleus pycnosis disappeared, but renal interstitial edema and inflammatory cell infiltration appeared. There was a large amount of glycogen deposition and high expressions of TUNEL positive cells and Hoechst33258 positive cells. Compared with CDDP group, the levels of BUN and CRE in GSLS treatment group significantly decreased (P<0.05, P<0.01) in serum, glycogen deposition was reducted and apoptosis of renal tubular epithelial cells decreased in kidney tissues (P<0.05). The level of TNF-α, IL-1β(P<0.05) and the degree of renal tissue necrosis were significantly reduced (P<0.05) in CDDP+GSLS 300 group, but there was a significant increase in the level of CAT and GSH (P<0.05). CONCLUSION GSLS can protect against mouse kidney injury induced by cisplatin. The mechanism may be related to oxidation, reduced inflammation reaction and resistance to apoptosis.

Aim To study the change of mutant pre- vention concentration (MPC) in carbapenem-resistant Acinetobacter baumannii (CRAB) treated with moxi- floxacin ( MFX ) and/ or cefoperazone/ sulbactam (CFS) in vitro, and provide a theoretical support for preventing the bacterial resistance. Methods To cal- culate the fractional inhibitory concentration (FIC) in- dex, the minimum inhibitory concentration (MIC) of 20 clinical isolates of CRAB treated with MFX and/ or CFS was determined by checkerboard microdilution as- say. In addition, to calculate the selection index (SI), the MPC of 20 clinical isolates of CRAB treated with MFX and/ or CFS was determined by agar plate di- lution assay. Results Our study showed that there was synergistic/ addictive action, rather than antago- nism action against clinical isolates of CRAB when treated with MFX + CFS. The SI of the 20 isolates trea- ted with MFX or CFS alone was 4 ~128 and 8 ~64 re- spectively, but reduced to 1 ~8 and 4 ~16 when trea- ted with MFX + CFS, which decreased by 2 ~16 and 2 ~4 times respectively compared with the single treat- ment. Conclusion These results suggest that the combination treatment of MFX + CFS against clinical isolates of CRAB might lower the MPC of the isolates treated with MFX/ CFS alone, narrow the mutant selec- tion window, and prevent the generation of drug - re- sistant mutants.

To explore the anticancer effect of curcumin on human B cell non-Hodgkin's lymphoma and compare its effects on human B cell non-Hodgkin's lymphoma cells and normal peripheral blood mononuclear cells (NPBMNCs). MTT assay was used to study the effect of curcumin on the growth of Raji cells and NPBMNCs. The effect of curcumin on the apoptosis of Raji cells and NPBMNC were studied by flow cytometry and TDT-mediated dUTP nick and labeling (TUNEL). The effect of curcumin on the cell cycle of Raji cells were examined by propidium iodide staining flow cytometry. The results showed that curcumin strongly inhibited proliferation of Raji cells, 24 h IC50 for Raji cells was 22.8 +/- 1.82 micromol/L and curcumin induced Raji cell apoptosis in a time- and dose-dependent manner. Raji cells treated with curcumin showed G0/G1 or G2/M phase increase and S phase decrease. However, curcumin did not demonstrate apparent proliferation inhibition and apoptosis induction in NPBMNCs. It was concluded that curcumin is able to inhibit the proliferation of Raji cells by regulating the cell cycle and inducing the cell apoptosis. Morever, curcumin has low toxicity on NPBMNCs but can selectively induce apoptosis in Raji cells.
Antineoplastic Agents, Phytogenic/*pharmacology ; Apoptosis/*drug effects ; Cell Cycle/drug effects ; Cell Proliferation/drug effects ; Curcumin/*pharmacology ; Dose-Response Relationship, Drug ; Lymphoma, B-Cell/*pathology ; Tumor Cells, Cultured

The anticancer activity of trichostain A (TSA) on human B cell non-Hodgkin's lymphoma and its mechanism were explored. The effect of TSA on the growth of Raji cells and normal peripheral blood mononuclear cells (NPBMNC) was studied by MTT assay. The effect of TSA on the apoptosis of Raji cells and NPBMNC was studied by flow cytometry and TDT-mediated dUTP nick end labeling (TUNEL). The effect of TSA on the cell cycle of Raji cells was studied by propidium iodide method. The results showed that TSA potently inhibited proliferation of Raji cells at microgram concentrations and induced apoptosis of Raji cells in a time- and concentration-dependent manner. Treatment with TSA induced accumulation of cells in G0/G1 or G2/M and a concomitant decrease of cell population in S phase. However, NPBMNC was less sensitive to the cytotoxic effect of TSA than Raji cells. It was concluded that TSA may inhibit the proliferation of Raji cells by regulating the cell cycle and inducing the cell apoptosis. Moreover, TSA demonstrates low toxicity in NPBMNC but selectively induces apoptosis of Raji cells.

Objective To evaluate the efficacy and safety of Paclitaxel drug coated balloon (DCB) (SeQuent Please) in an elderly patients with de novo coronary disease.Methods We performed a retrospective study of 158 consecutive patients (63 patients aged ≥65 yrs and 95 patients aged ＜65 yrs) received DCB therapy in Cath Lab of Beijing Hospital.Clinical characteristic was recorded and coronary angiography was analyzed with quantitative coronary angiography (QCA) software.Results In elderly group,more patients have hypertension (65.1％ vs.56.8％),atrial fibrillation (7.9％ vs.2.1％),previous percutaneous coronary intervention (PCI) history (44.4％ vs.23.2％,P＜0.01) and non ST-elevated myocardial infarction (NSTEMI) (14.3％ vs.4.2％,P ＜0.05).In non-elderly group,more patients were male (71.6％ vs.50.8％,P＜0.05) and current smoker (52.3％ vs.30.2％,P＜ 0.01).Old patients had more complicated lesions,especially calcified lesions (36.8％ vs.14.0％,P＜0.01).Despite of that,our study showed a higher success rate of PCI in elderly group.Both groups of patients showed significant acute gain in minimal lumen diameter (MLD) after DCB released.At 4 days post-operation,there was one case that underwent acute myocardial infarction requiring emergent target lesion revascularization (TLR) in non-elderly group.No major adverse cardiac event (MACE) was observed in the elderly group during hospitalization.Twenty-one patients underwent coronary angiographic followed up at average 9 months post PCI.The QCA analysis showed that MLD of lesions treated with DCB had mildly increased [(2.00±0.67) mm vs.(1.91 ± 0.47) mm,P＞0.05],the late lumen loss (LLL) was (-0.09±0.50) mm.At 9 months follow-up,the MACE rate in the elderly group was 1.6％ and 1.1％ in non-elderly group,with TLR rates at 0.0％ and 1.1％ respectively (both P＞0.05).No death was observed in either group.Conclusions The efficacy and safety of DCB on the elderly patients with de novo lesions is as good as non-elderly patients despite more complex anatomy and comorbidities.

This study was aimed to find the relationship between lung function injured characteristic of ulcerative colitis (UC) and endoscopic index. It will verify and enrich Chinese medicine theory to guide clinical diagnosis and treatment. UC patients without respiratory system diseases were selected between September 2009 and March 2011 from several triple-A hospitals in China. Furthermore, disease history, lung function, colonoscopy and histopathology were taken. The results showed that among 171 enrolled cases, there were statistical differences in endoscopic index of residual-function and diffusion-function between the abnormal group and the normal group (P< 0.05). The resid-ual-function group was r = 0.003. There were no statistical differences in ventilatory-function and small-airway-function in the abnormal group. It was concluded that there were different types of injured lung function in UC. A-mong them, the abnormalities of residual-function and diffusion-function had strong correlation with the intestinal damage degree. The change on residual-function was more obvious.

To explore the anticancer effect of curcumin on human B cell non-Hodgkin's lymphoma and compare its effects on human B cell non-Hodgkin's lymphoma cells and normal peripheral blood mononuclear cells (NPBMNCs). MTT assay was used to study the effect of curcumin on the growth of Raji cells and NPBMNCs. The effect of curcumin on the apoptosis of Raji cells and NPBMNC were studied by flow cytometry and TDT-mediated dUTP nick and labeling (TUNEL). The effect of curcumin on the cell cycle of Raji cells were examined by propidium iodide staining flow cytometry. The results showed that curcumin strongly inhibited ±1.82 μmol/L and curcumin induced Raji cell apoptosis in a time- and dose-dependent manner. Raji cells treated with curcumin showed curcumin did not demonstrate apparent proliferation inhibition and apoptosis induction in NPBMNCs. It was concluded that curcumin is able to inhibit the proliferation of Raji cells by regulating the cell cycle and inducing the cell apoptosis. Morever, curcumin has low toxicity on NPBMNCs but can selectively induce apoptosis in Raji cells.

An HPLC pre-column derivatization detection method was established to detect and analyze the formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 from different manufacturers.The effects of aldehyde and acetaldehyde on the aggregation of adalimumab under different conditions were monitored.Based on the control of genotoxic impurities and the influence on the stability of monoclonal antibody preparations, the control limits of the two chemicals were preliminarily obtained.2, 4-dinitrophenylhydrazine (2, 4-DNPH) was applied as the derivatization reagent in HPLC pre-column derivatization; acetonitrile and water were used as mobile phase to perform a gradient elution on a C8 (4.6 mm × 150 mm, 5 μm) chromatographic column.The detection wavelength was 360 nm, and the external standard method was used for quantification.Verification results showed that the method was suitable for the quantitative analysis of trace formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 . The detection and analysis of formaldehyde or acetaldehyde in different batches of polysorbate 80 and polysorbate 20 from different manufacturers showed that the content of formaldehyde and acetaldehyde were quite different. The content of formaldehyde and acetaldehyde in polysorbate 80 were significantly higher than those of polysorbate 20. After monitoring the changes of adalimumab aggregates treated by formaldehyde and acetaldehyde by size exclusion chromatography (SEC), it was found that the effect of formaldehyde on adalimumab aggregation was significantly higher than that of acetaldehyde.According to the requirements of ICH M7 (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk), the impurity limits of formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 for monoclonal antibody preparations were calculated from the perspective of risk assessment.Combined with the influence on the aggregation stability of monoclonal antibodies, the preliminary limis for acetaldehyde and acetaldehyde were recommended to be ≤ 7 μg/g and ≤ 765 μg/g, respectively.

Objective To investigate the intervention effects ofYinao Jieyu Prescription on the behaviors and damages in hippocampal CA1 area of the rats with post-stroke depression (PSD).Methods Totally 168 SPF male SD rats were randomly divided into normal group, sham-operation group, stroke group, PSD group, Western medicine group and TCM group. There were 24 rats in the normal group and sham-operation group, and 30 rats in the other groups. Rats in the normal group received no intervention. Rats in the sham-operation group received no suture. Rats in the stroke group were given middle cerebral artery occlusion operation and normally fed after operation. Rats in the PSD group, Western medicinal group and TCM group were made into PSD models by chronic immobilization stress for one week and individual battery to the end. At the inception of modeling, Western medicine group received fluoxetine hydrochloride for gavage; TCM group receivedYinao Jieyu Prescription for gavage; other groups received distilled water for gavage, once a day. At the end of week 2, 4, and 8, the morphology of the hippocampal CA1 area in each rat was observed by microscope after HE stained.Results Except for the week 2, at the same time point, the behavior scores of the rats in the TCM group were higher than those in the PSD group. At the same time point, the CA1 region of the hippocampus in the TCM group was more complete than the PSD group, and the cells were arranged neatly and in normal morphology.ConclusionYinao JieyuPrescription can improve the symptoms of PSD rats, and has protective effects on hippocampal CA1 area.