CpG island methylator phenotype (CIMP) refers to a set of multiple gene promoter CpG island methylation phenotype which exists in tumor at the same time.Many studies show that CIMP is ubiquitous in gastric cancer,which is related to the pathogenesis,diagnosis,patient's condition,prognosis and curative effect of gastric cancer.

Animals ; Humans ; Hyperbaric Oxygenation ; Mandibular Diseases ; prevention & control ; therapy ; Osteoradionecrosis ; prevention & control ; therapy ; Radiation Injuries ; prevention & control ; therapy

Aim: To improve the solubility, dissolution and bioavailability of lycopene by preparing lycopene solid dispersion. Methods: Lycopene solid dispersion was prepared by the solvent method using Poloxamer 188 as car-rier. The physicochemical characteristics of the dispersion were determined by DSC, ultraviolet-visible spectra and the Dissolution Apparatus Ⅱ( Paddle). The oral bioavailability of lycopene was estimated in rat after oral dosing of lycopene solid dispersion or oil preparation. The plasma concentrations of lycopene in rats were determined by HPLC. The pharmacokinetic parameters were estimated by Kinetica software package. Results: In vitro dissolution of lycopene solid dispersion was greater than those of lycopene (raw material), and the physical mixture of lyco-pene and Poloxamer 188, partly due to the existing molecular state of lycopene in the dispersion. It was also found that the relative bioavailability of lycopene solid dispersion to lycopene oil preparation was (312. 2±96. 9) % . The optimal ratio of lycopene to carrier in the dispersion was about 1: 5. Conclusion: Lycopene-Poloxamer 188 solid dispersion could be prepared by the proposed simple, low-costly procedure resulting in improved bioavail-ability of lycopene, which is worthy of further development.

The goal of this work was to explore the prospect of standardized application of an in-vitro bioactivity assay for recombinant human follicle-stimulating hormone based on a reporter gene. The relative accuracy, intermediate precision, linearity and applicable range of the method were validated according to the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Three laboratories used this method to determine the in-vitro biological activities of six batches of drug product and three batches of drug substance manufactured by two different companies. The consistency of the potency determined by three laboratories, the intra-laboratory precision and inter-laboratory precision were analyzed. The method was optimized during the collaborative validation. The results of method validation meet the requirements of the General Rules of Chinese Pharmacopoeia 2020 edition Volume IV (9401). Aiming to resolve the problems found in the collaborative validation, the medium for cell seeding, the pre-diluted buffer solution of standard and sample, and the means of removing and discarding supernatant after stimulation were optimized. After optimization, there was no significant difference in the bioactivity among the different laboratories (P > 0.05), indicating statistical equivalency. Intra-laboratory and inter-laboratory precision were good and the geometric coefficient of variation (GCV%) were both less than 15%. In conclusion, the reporter gene assay has good intra-laboratory repeatability and inter-laboratory reproducibility and is suitable for analyzing recombinant human follicle-stimulating hormone drug product and drug substance by different manufacturers. It is expected to be used as a standardized method for the determination of the in-vitro bioactivity of such products.

Cell Line, Tumor ; Enzyme Inhibitors ; pharmacology ; Heterocyclic Compounds, 1-Ring ; pharmacology ; Humans ; Proteasome Endopeptidase Complex ; drug effects

This study is to investigate the influence and mechanism of action of asymmetrical dimethylarginine (ADMA) and the induced oxidative stress level on Alzheimer's disease (AD) incidence. ADMA concentration, nitric oxide, Abeta(40)/Abeta(42) ratio, inducible NO synthase (iNOS) activity and the concentrations of the induced free radicals including malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and peroxynitrite (ONOO-) in the cerebrospinal fluid (CSF) from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients, and it showed negative correlation with the NO, iNOS activity, and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Abeta(40)/Abeta(42) ratio (P<0.01) with the observation that Abeta(40)/Abeta(42) ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA, 3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence, and their joint regulation may provide new idea for the prevention and clinical treatment of AD.

Adolescent ; Adult ; Aged ; Facial Nerve ; anatomy & histology ; pathology ; Female ; Humans ; Male ; Microsurgery ; Middle Aged ; Parotid Neoplasms ; surgery ; Young Adult

Objective To compare the effect of perioperative intravenous injection of Analgecine on the analgesic efficacy and complications of patient-controlled intravenous analgesia ( PCIA ) of different doses of fentsnyl in postoperative lumhotomy patients.Methods 200 patients underweat hmbotomy in general anesthesia were randomly divided into four groups with fifty cases each.Fentanyl 1.0mg in group A,fentanyl 0.5mg in group B,fentanyl 1.0mg in group C,fentanyl 0.5mg in group D.The drugs in each group were diluted to 100ml and infused by pumps.Besides,the patients in group C and D were injected with analgecine 3.6u and 7.2u at the night before the operation,preoperation and postoperation respectively.The visual analog scale(VAS),times of PCA and incidence of side effects were recorded during the period of postoperative 24 hours.Results The VAS of group B at 2h after operation was (5.2 ± 1.9 ) points,which was significandy higher than that of group A,C and D( P ＜ 0.05 ),VAS became similar 4h later( P ＞0.05).The demanding times for supplemental bolus in group B were also significantly higher than that of A,C and D( P ＜ 0.05 ).The incidence of nausea,vomiting,itching,somnolence in group B and D were significantly less than those in group A and C( P ＜0.05 ).No respiratory depression or abnormal bleeding occurred in the four groups.Conclusion Perioperative intravenous injection of analgecine had a better effect on PCIA of fentanyl and could reduce fentanyl requirement and its side effects in lumbotomy patients.

The studies have shown that the genesis and development process of breast cancer is closely related with microRNAs (miRNAs).Multiple miRNAs are involved in the progress of the incidence of breast cancer,and can be used to assess the prognosis,clinical treatment of breast cancer,and to explore the resistance mechanisms.

BACKGROUND: Multipotency of hepatic stem cells is of important value in liver transplantation. Stem cells have been successfully identified and isolated from the animal livers. However, reports on whether stem cells exist in human hepatic tissue and how to isolate and identify them ars few.OBJECTIVE: This study was in attempt to isolate hepatic stem cells from human para-cancerous tissues of hepatoma and in vitro culture them, also to identify the stem cell surface marker, in order to find a new source of heptatic stem cells.DESIGN: Cell observation experiment.SETTING: Department of Common Surgery, First Hospital, Jilin University; Department of Common Surgery,Dongfeng Hospital of Traditional Chinese Medicine.PARTICIPANTS: Samples were harvested from 10 patients with hepatoma admitted to Department of hepatobiliary surgery, First Clinical College, Jilin University between October 2005 and June 2006, with age of 45 to 58 years.Hepatic tissue 2 cm away from cancer nest was cut when patients underwent hepatectomy, and it was pathologically confirmed as carcinoma-free tissue. Written informed consents were obtained from each patient. DMEM/F12 dry powder used for cell culture was provided by Hyclone Company, USA. Fresh fetal bovine serum was prepared by Lianxing Biotech Co.,Ltd, Tianjin. Various cell growth factors were the products of Cytolay Company, USA.METHODS: Para-cancerous tissues of hepatoma was cut into pieces, rinsed with Hank's solution and digested with type Ⅳ collagenase. Then the isolated cells were re-suspended in the DMEM/F12 medium supplemented with 0.1 volume fraction of fetal bovine serum, and hepatocyte growth factors, epidermal growth factors and α- fibroblast growth factors of 25 μg/L each were added in the above medium. When the cultured cells covered 2/3 of bottom,they were digested with trypsinase for passage and inoculated at 2×107 L-1. When cells propagated to the 3rd and 4th generations, 2.60×109 L-1 cell suspension prepared with trypsinase was added, and subsequently, anti-human C-kit antibody, immunomagnetic beads and Buffer solution were added in order. C-kit+ cells were preliminarily isolated by immunomagnetic bead separation. Haematoxylin-eosin staining and immunofluorescent histochemical double-staining were used for detecting the hepatic stem cells in para-cancerous tissues.MAIN OUTCOME MEASURES: ① Observation of cell morphology. ② Identification of hepatic stem cells from para-cancerous tissues. ③ Identification of C-kit+ cells by immunofluorescent histochemical double-staining.RESULTS :① After primarily cultured for 2 weeks, the adherent cells grew in colony. After one half of culture medium was renewed, mature hepatocytes were gradually broken and disappeared. Small round cells propagated, and most of them were located in the center and arranged in cluster. Most cells were found with one big nucleus in each, less cytoplasm and clear cell boundary. When cells propagated to the 1st and 2nd generations, they still grew in colony, but fast. Each C-kit+ cell isolated by immunomagnetic bead separation presented a spherical cell body with a very big nucleus and less cytoplasm. After in vitro cultured for 1 week, it presented broken pieces and apoptotic symptoms.② After para-cancerous tissue was stained by haematoxylin-eosin, atypically proliferated biliary tracts with small round cells could be seen in the portal area. After para-cancerous tissue was stained by immunofluorescent histochemical double-staining, small round cells in the biliary tracts proliferated in the portal arsa co-expressed red fluorescence AFP and green fluorescence cytokeratin (CK) 19 with yellow superposition arsa. ③ After C-kit+ cells were stained by fluorescence immunocytochemisty, cytoplasm expressed alpha-fetoprotein (AFP) red granules and CK19 green granules. The superposition area of both presented yellow fluorescence of AFP+/CK19+-positive cells.CONCLUSION: Hepatic stem cells exist in human para-cancerous tissues of hepatoma. Therefore, expressions of C-kit+/AFP+/CK19+, the surface markers of hepatic stem cells, can be used for identifying and isolating hepatic stem cells. Small round cells obtained by in vitro isolation and culture, i.e. hepatic oval cells possess bipotential differentiation of hepatocyte and hepatobiliary epithelial cells.