Objective To investigate the role of neuro-specific DNA repair gene Nbn in mouse hippocampus development by observing the morphological differences in Nbn-CNS-Del and Nbn-CNS-Ctr mice.Methods Serial sections and stereology were used to quantitatively analyze the development of mouse hippocampus on postnatal day 7,14 and 21.Results Compared with that of the control group,the hippocampus development of Nbn-CNS-Del mice lagged behind.In Nbn-CNS-Del mice,on day 21,the profile area of pyramidal layer of hippocampus and granular layer of dentate gyrus decreased(P

Rofecoxib, a COX-2 specific inhibitor, is approved for treatment of osteoarthritis, acute pain and primary dysmenorrhea. On September 30, 2004, Merck announced the voluntary worldwide withdrawal of rofecoxib (Vioxx). This paper reviewed the pharmacological actions of the COX-2 specific inhibitors and the characterization, premarket study, clinical application and side-effects of rofecoxib and analyzed the withdrawal of rofecoxib.

BACKGROUND: It is a new tendency to treat central nervous system injury or tumor therapy using the combination of seed cells and gene therapy.OBJECTIVE: To observe the dose-relationship between transfection and expression of rabbit bone marrow mesenchymal stem cell (BMSCs) with adenovirus vector carrying green fluorescent protein (Ad-GFP), and to study its effects on cell biological properties, in addition, to explore the feasibility of using Ad-GFP vector to construct gene modified BMSCs.DESIGN, TIME AND SETTING: A randomized grouping, contrast observation. The experiment was performed at the Southern Medical University between August 2008 and March 2009.MATERIALS: New Zealand white rabbits, irrespective of genders, weighing 2.0-3.0 kg, were selected.METHODS: BMSCs were separated and cultured in vitro, and then the cell immunophenotypes were detected by flow cytometry.The adenovirus was obtained by packaging 293 cells and was used to transfect BMSCs with various liters (1 ×-10~3-1×10~(10) PFU/mL).Cytometry was used to analyze the transfection efficiency.MAIN OUTCOME MEASURES: Cell morphological changes were detected under an invert microscope. The cell proliferation was detected by CCK8 kits. BMSCs transfected with Ad-GFP were induced differentiating into neuron-like cells by adding of β-mercaptoethanol.RESULTS: The surface markers of 3-6-generation BMSCs were negative to CD34 and CD45, but positive for CD29 and CD44.When the virus titers were 1 ×10~7 PFU/mL, the transfection rate was 55%, which were 85% when the virus titers were 1 ×10~9 and1×10~(10) PFU/mL. However, cell pathology phenomenon occurred when the virus titer was 1 ×10~(10) PFU/mL. The fluorescence was strongest expressed at day 7, and it still can be seen at day 28. The BMSCs trasfected with Ad-GFP could differentiate into neuron-like cells under induction of p-mercaptoethanol, with positive neuron-specific enolase.CONCLUSION: Ad-GFP with suitable titers can infect BMSCs effectively with little influence on the biology property or differentiation function. BMSCs can serve as seeds cell in gene therapy field when utilizing ad-GFP vector system.

AIM To prepare D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-modified artesunate liposomes and to investigate the in vitro anti-tumor activity.METHODS The liposomes prepared by thin-film dispersion method were characterized by transmission electron microscopy and particle size analyzer,and the encapsulation efficiency was determined by ultrafiltration centrifugation.The liposomes' cytotoxicity to human hepatoma HepG2 cells was evaluated by MTT method.RESULTS The average particle size,PDI,Zeta potential,encapsulation efficiency,drug loading of the liposomes were 126.7 nm,0.182,-10.1 mV,78.8％ and 18.38％,respectively.The liposomes displayed a significant inhibition on HepG2 cells with the IC50 value of 0.034 μmol/mL.CONCLUSION Compared with non-TPGS-modified artesunate liposomes,the TPGS-modified artesunate liposomes prepared by this method afford smaller vesicle size,better stability and higher encapsulation efficiency with stronger in vitro anti-tumor activity.

AIM: To study the methodology of hepatic cytochromes P450 in Wistar rats. METHODS: After the Wistar rats were administered with gatifloxacin and ciprofloxacin once daily for 7 days,and liver microsome was distilled by different velocity centrifugation. The Lowry method was used to measure the concentration of protein in liver microsome,and the activities of gatifloxacin in hepatic microsomal enzymes (CYP450) of rats were studied by spectrophotometer. RESULTS: The linearity range of ox blood serum albumin standard curve was 25-250 mg?L -1 with the detection limits 25 mg?L -1 and correlation coefficient 0.9988 . The contents of cytochromes P450 and cytochromes b5 and the activity of NADPH-cytochrome C reductase indicated that ultraviolet spectrophotometer method was sensitive. The linearity range of formaldehyde standard curve,which was used to measure the activities of aminopyrine-N-demethylase and erytheomycin-N-demethylase was 0.05 - 0.5 mmol?L -1 with the detection limits 0.05 mmol?L -1 and correlation coefficient 0.9998 . The linearity range of resorufin standard curve,which was used to measure the activity of Coumarin 7-hydroxylation was 1-8 ?mol?L -1 with the detection limits 1 ?mol?L -1 and correlation coefficient 0.9998 . CONCLUSION: The methods of measuring the contents and activities of the six hepatic microsomal enzymes are sensitive and credible in Wistar rats by ultraviolet and fluorescence spectrophotometer.

Background and purpose:Myelosuppression is the most common dose-limiting toxicity of tumor chemotherapy in which leukocytopenia and neutropenia are the most common conditions. Not only are up-titrations of the doses of chemotherapeutic drugs limited, but also normal process of the chemotherapy is affected. Filgrastim-Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) has the activity of stimulating the formation of granulocyte colony and promoting the growth, proliferation and differentiation of granulocytes which can be signiifcantly effective on leukocytopenia and neutropenia induced by chemotherapy. In this study, we observed the leukogenic effects, toxic and side effects of low, medium, and high doses of rhG-CSF used prophylactically after chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), to explore a rational application strategy for rhG-CSF..Methods:One hundred and twenty six patients with pathologically proved advanced non-small cell lung cancer (NSCLC) under chemotherapy were digitally randomized to A, B and C groups. Filgrastim was given to patients of the three groups 24h after the end of chemotherapy. The dosages are: Group A (low dose): 300 μg of Filgrastim, s.c., qd × 1 day; Group B (medium dose): 300 μg of Filgrastim, s.c., qd × 2 days; Group C (high dose): 300 μg of Filgrastim, s.c., qd × 3 days. Then the signs and symptoms as well as toxic and side effects of Filgrastim after medication were observed.Results:Prophylactic usage of medium and high dosages of rhG-CSF could maintain WBC count at no less than 4.0×109/L in nearly 60% of patients. In patients with Grade III leukopenia, more days were needed for recovery of white blood cell (WBC) count with the low dose, while signiifcantly (P<0.05) less days were needed with the high dose. In view of the dynamic changes of neutrophil(ANC), additioning of the high dose of rhG-CSF after chemotherapy could increase the average level ofANC, notably shortening the duration of lowANC caused by chemotherapy. The incidence of infections was 4.76% for the 126 patients as a whole, 9.52% for the low dose group, and 4.76% for the middle dose group. The patients could tolerate the slight side effects incurred during treatment with Filgrastim.Conclusion:All of the three doses (low, medium, and high) of prophylactic administration of Filgrastim after chemotherapy can promote recoveries of WBCs and neutrophil granulocytes and reduce opportunities of infections. High doses of rhG-CSF can be faster and safer in increasing WBCs and neutrophil granulocytes.

?AIM:To evaluate the objective visual quality of patients who underwent corneal cross-linking for the keratoconus using double-pass analysis system.? METHODS: Advanced keratoconus patients who underwent UV - riboflavin corneal cross - linking from January to July 2015 were included. The outcomes of their objective scattering index ( OSI ) , predicted visual acuity ( VA ) , the cut - off frequency of modulation transfer function ( MTF cut- off ) , the Strehl ratio ( SR ) were compared before and 6mo after corneal cross-linking.?RESULTS: A total of 13 patients ( 16 eyes ) were included. There was no statistically significant difference between pre- and 6mo postoperative data in uncorrected visual acuity, best corrected visual acuity, refractions and mean value of Sim-k (P>0. 05). Non-invasive average tear film break up time ( NIAvg-BUT ) detected by the Sirius system decreased after corneal cross-linking ( P<0. 05 ) . Using double - pass analysis system, no statistically significant change was found in MTF cut off, Strehl Ratio, OSI before and after treatment(P>0. 05). Tear Film Analysis Mean OSI increased at 6mo postoperatively (P<0. 05).? CONCLUSION: The subjective visual quality isn’t effected by corneal cross-linking. The tear stabilities of patients are influenced by these operations at 6mo postoperatively. More observations on long-term effect are needed to be taken in the future.

Objective:To evaluate the effects of dexamethasone on systemic lupus erythematosus complicated with cognitive dysfunction.Methods:Ten wild type mice and 20 MRL/lpr mice were applied for the research.MRL/lpr mice were randomly assigned to a MRL/lpr group and a MRL/lpr + dexamethasone (1.5 mg/kg) group.Interleukin-6 (IL-6),IL-1β,and tumor necrosis factor alpha (TNF-α) in serum and hippocampus were detected.The protein phosphorylation levels of phosphoinositide 3-kinase (P-PI3K),protein kinase B (P-Akt),NF-kappa-B inhibitor alpha (P-IκBa) and nuclear transcription factor kappa-B p65 (P-NF-κB p65) were detected by Western blot,the level of P-NF-κB p65 also was detected by immunohistochemistry.Results:Treatment with dexamethasone (1.5 mg/kg) alleviated the cognitive dysfunction and decreased the levels of IL-6,IL-1 β and TNF-α in serum and hippocampus,and reduced the levels of P-PI3K,P-Akt,P-IκBa and P-NF-κB p65 in hippocampus in MRL/lpr mice.Conclusion:Dexamethasone may play a protective role in the cognitive function by decreasing the levels of TNF-α and IL-1 β in the hippocampus of MRL/lpr lupus mice.

We used metabolomics to investigate the ability of a traditional Mongolian medicine called modified Tabusen-2 (MT-2) to improve kidney yang deficiency (KYD) in rats. All animal experiments were conducted under the guidance and standards of the Medical Ethics Committee of Inner Mongolia Medical University. SD rats were divided into 6 groups of six rats: a normal group, a model group, Jinkuishenqi pill administration group (1.26 g·kg^-1), and MT-2 administration in high-, medium- and low-dose groups (1.512, 0.756, and 0.378 g·kg^-1). KYD was established by intramuscular injection of hydrocortisone (HC) and biochemical indicators and clinical characterization was used to confirm that KYD was established. All groups received intragastrically administered drug (Jinkuishenqi pill or MT-2) or saline. Serum from each group was collected after 8 weeks and analyzed by UPLC-Q-exactive-MS to measure various biochemical indicators. The biomarkers affected by MT-2 were identified and the metabolic pathways of KYD regulated by MT-2 were analyzed by metabolomic analysis. The results show that MT-2 can decrease serum creatinine (Cr) in KYD rats and significantly increase (P<0.05) the content of thyroid stimulating hormone (TSH) and luteinizing hormone (LH). In serum samples, 38 biomarkers such as corticosterone, L-phenylalanine, and DL-tryptophan were measured as possible indicators for disease development in KYD rats. MT-2 lowered 18 biomarkers of KYD, including corticosterone, deoxycorticosterone, and L-phenylalanine, and altered 13 related metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and steroid hormone biosynthesis, resulting in an overall improvement in KYD. MT-2 appears to be important in improving KYD in rats mainly by regulating metabolites such as amino acids, steroids and lipids.

OBJECTIVETo observe clinical characteristics of herb-induced liver injury (HILI).

METHODSGeneral conditions, medical history, clinical manifestations, biochemical indices, prognosis, and Roussed Uclaf Causality Assessment Method (RUCAM) scores were retrospectively analyzed in 595 inpatients at 302 Military Hospital between January 2009 and January 2014.

RESULTSThere were 423 cases (accounting for 71.1%) were females with multiple onset age ranging 41 to 50 years old. The median time from starting Chinese herbs to the occurrence of liver injury (LI) was 30 days (15-75 days), and 511 cases (85.9%) were classified as hepatocellular injury. Chinese herbs inducing HILI were mainly used for skin disease (102 cases, 17.1%), osteoarticular disease (57 cases, 9.6%), and gastrointestinal disease (49 cases, 8.2%), covering 207 kinds of Chinese patent medicines. Polygonum multiflorum, Psoralea corylifolia, and Corydalis ambigua were often seen in Chinese prescriptions. In RUCAM scoring, 451 HILI patients (accounting for 74.1%) were very possibly associated with Chinese herbs. Liver failure occurred in 47 HILI patients (accounting for 7.9%), cirrhosis in 45 patients (accounting for 7.6%), chronic HILI in 80 patients (accounting for 13.4%), 27 (4.5%) died, and only 2 (0.3%) underwent liver transplantation.

CONCLUSIONSChinese herbs could cause LI or even death. Attention should be paid to herbal hepatotoxicity and improving monitoring system of HILI.