Aged ; Female ; Humans ; Infant ; Lung Diseases ; diagnostic imaging ; Male ; Pulmonary Artery ; diagnostic imaging ; Tomography, X-Ray Computed

A series of cycloberberine derivatives were designed, synthesized and evaluated for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e and 6g showed strong inhibition on human HepG2 cells. They afforded a potent effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g using flow cytometry assay. It significantly inhibited the activity of DNA Top I at the concentration of 0.1 mg mL-1. Our results provided a basis for the development of this kind of compounds as novel anti-cancer agents.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type I ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Molecular Structure ; Structure-Activity Relationship

OBJECTIVETo investigate the genotoxicity and oxidative stress induced by copper oxide nanoparticles in mice.

METHODSThirty mice were randomly divided into control group and low- and high-dose exposure groups. The low- and high-dose exposure groups were given copper oxide nanoparticles (50 and 150 mg/kg) by a single intraperitoneal injection, while the control group was given an equal volume of normal saline containing 0.05%Tween 80. The micronucleus rate of reticulocytes in peripheral blood from the caudal vein and urinary 8-hydroxy-deoxyguanosine (8-OH-dG) level were measured before and at 24, 48, and 72 h after exposure. All the mice were sacrificed at 72 h after exposure, the liver, kidney, and femoral marrow were taken for DNA extraction, and 8-OH-dG in DNA was quantified.

RESULTSThe micronucleus rates of peripheral blood reticulocytes in low-dose exposure group at 48 h (3.11±1.46‰ and in high-dose exposure group at 24 and 48 h (4.25±0.43) and 5.42±0.76‰) were significantly increased compared with those before exposure (1.55±0.39‰ and 1.11±0.19‰) and those in control group (1.55±0.28‰ and 1.00±0.67‰) (P < 0.05 or P < 0.01). The urinary 8-OH-dG levels (ng/mg creatinine) in low- and high-dose exposure groups at all time points were significantly increased compared with those before exposure and those in control group (P < 0.05 or P < 0.01). The low- and high-dose exposure groups had significantly higher content of 8-OH-dG in liver DNA than the control group (4.53±1.27 and 7.69±2.78 vs 0.85±0.14, P < 0.01).

CONCLUSIONCopper oxide nanoparticles cause genotoxicity and increase oxidative stress in mice.

Animals ; Copper ; toxicity ; DNA Damage ; drug effects ; Female ; Male ; Mice ; Mice, Inbred ICR ; Nanoparticles ; toxicity ; Oxidative Stress ; drug effects

OBJECTIVETo study the effect of gastrin on the mRNA and protein expression of urokinase-type plasminogen activator (u-PA) in human colon cancer cells and detect the role of p38 MAPK in this process.

METHODSLipofectin method was used to transfect pCR3. 1/CCK2R vector expressing gastrin receptor into a colon cancer cell line colo320. Gastrin and gastrin antagonist were used to up-regulate and down-regulate the signaling pathway, respectively. Human colon cancer colo320 cells and colo320/ CCK2,R cells were cultured and then stimulated with gastrin for different time; SB203580 was added into culture medium to prevent p38 kinase pathway before incubating with gastrin; Western blot and RT-PCR were used to examine the u-PA expression. Western blot was employed to detect p38 kinase phosphorylation.

RESULTSGastrin increased evidently the mRNA and protein expressions of u-PA and induced p38 kinase phosphorylation in colo320/CCK,R cells time-dependently. However, the extent of enhancement of u-PA and p38 MAPK expression in colo320 cells was much less than that in colo320/CCK2R cells. The gastrin antagonist L-365, 260 showed an effect of competitive inhibition on gastrin-induced u-PA expression and p38 kinase phosphorylation. The inhibitor SB203580 could sufficiently suppress gastrin-induced p38 kinase phosphorylation and significantly attenuate gastrin-induced u-PA mRNA and protein expressions in colo320/ CCK2 R cells in a dose-dependent manner.

CONCLUSIONGastrin-gastrin receptor signal transduction pathway can obviously induce u-PA expression in human colon cancer cells via activating the phosphorylation of p38 kinase.

Benzodiazepinones ; pharmacology ; Blotting, Western ; Cell Line, Tumor ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; Gastrins ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Genetic Vectors ; Humans ; Imidazoles ; pharmacology ; Phenylurea Compounds ; pharmacology ; Phosphorylation ; drug effects ; Pyridines ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Receptor, Cholecystokinin B ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Transfection ; Urokinase-Type Plasminogen Activator ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective: To investigate the relationship between menopausal status at different FPG levels and the risk of new onset of impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM). Methods: Female subjects were selected from the females who joined in the epidemiological survey between May and September in 2009 in six counties of Guanlin Village and Xushe Village in Yixing City in Jiangsu Province by cluster sampling method. Subjects with diabetes at baseline or pre-menopause with age above 65 years old or surgical menopause were excluded. Finally there were 2 084 eligible subjects included in this study. According to FPG at baseline, subjects were categorized into two groups as normal FPG group (FPG<5.6 mmol/L) and IFG group (5.6≤FPG≤6.9 mmol/L). Follow-up study was conducted from May in 2014 to January in 2016. Cox regression model was used to investigate the association between menopausal factors and IFG and T2DM among groups based on FPG. Results: The average age of subjects at baseline was 58.08 (51.74-65.82) years old, and the number of post-menopausal women was 1 631 (78.3%). The number of subjects in normal FPG group was 1 569 (75.3%), and in IFG group was 515 (24.7%). There were 104 subjects with new onset T2DM among which 34 subjects from normal FPG group and 70 subjects from IFG group. And there were 199 subjects with new onset IFG in normal FPG group. Among subjects with normal FPG, the incidence density of IFG in post-menopausal women (2 752/100 000 person-years) was statistically higher than that in premenopausal women (1 670/100 000 person-years) (P<0.001). After age and BMI adjusted, post-menopausal women had a higher risk of having IFG in normal FPG subjects with hazard ratio (HR) at 2.60 (P<0.001). Among subjects with normal FPG, the risk of new onset IFG decreased in post-menopausal women with menopause age increasing after age and BMI adjusted, with HR at 0.96 (P=0.046). No statistical association was found between menopausal factors and risk of T2DM either in the overall subjects or in the subgroups(P>0.05). Conclusion Menopause can increase the risk of IFG incidence in subjects with normal FPG. The incidence of IFG decreases with the menopause age increasing.

We isolated and identified the genotypes and molecular characteristics of the imported B3 measles virus (MeV) in the Chinese mainland. The Vero/SLAM cell line was used to isolate the viruses. Reverse transcription-polymerase chain reaction was undertaken to amplify the 450 nucleotide acids of the 3-terminal of the nucleoprotein gene. A phylogenetic tree was constructed and similarities in homology assessed. Results suggested that the Shanghai isolates MVi/Shanghai. CHN/38. 13/02 [B3] and MVi/Shanghai. CHN/40. 13/02[B3] were clustered within the same genotype group as the World Health Organization (WHO) B3 genotype reference strain. The number of differences in nucleotide acids between the two Shanghai isolates was one. The homology of nucleotide acids between the Shanghai isolates and the WHO B3 genotype reference strain (MVi/Ibadan. NGA/0.97/1/B3) was 98%. Comparative results from the Measles Nucleotide Surveillance system suggested that the sequences of Shanghai isolates and the 2013 vi- ruses from Australia, Japan, Korea, Hong Kong China, Philippines and Iran were identical. This is the first time that the B3 genotype of MeV in the Chinese mainland has been isolated since 1993. These data can be used to create a "baseline" of genetic information for measles viruses in China, and help to trace the transmission of measles viruses in China and the rest of the world.
China ; Genotype ; Humans ; Measles ; virology ; Measles virus ; classification ; genetics ; isolation & purification

Iron is an essential element for cell growing including tumor cells. This study was purposed to explore the effect of desferrioxamine (DFO) on cell line K562/A02 and its mechanism. K562/A02 cells were cultured with different concentrations of DFO. The inhibitory effects of adriamycin (ADM) used alone or combined with DFO on the proliferation of K562/A02 was evaluated by MTT assay. The apoptosis rate of K562/A02 cells after treatment with 0, 12.5, 25 and 50 µmol/L DFO alone or in combination with 1 mg/L ADM were analyzed by flow cytometry. ADM accumulation in K562/A02 cells after treatment with different concentrations of 0, 12.5, 25 and 50 µmol/L DFO were also analyzed by flow cytometry. The levels of BAX/BCL-2 and MDR1 mRNA were determined by RT-PCR, and then the protein level of P-glycoprotein (P-gp) was detected by Western blot. The results showed that the IC(50) of ADM for K562 and K562/A02 cells were (1.46 ± 0.07) mg/L and (40.98 ± 3.05) mg/L respectively. The resistance of K562/A02 cells to ADM was 28.06 times as that of K562 cells. After treatment of K562/A02 cell with DFO of 12.5, 25 and 50 µmol/L for 48 hours, the resistance of K562/A02 cells to ADM were increased by 24.95, 16.11 and 9.99 times respectively. When K562/A02 cells were incubated with different concentrations of DFO of 12.5, 25, 50 µmol/L for 48 hours, the apoptosis rat were (3.50 ± 0.30)%, (7.27 ± 0.32)% and (12.53 ± 1.21)% respectively. After co-culture with DFO and ADM for 48 hours, apoptosis rate were (6.13 ± 0.29)%, (9.57 ± 0.40)% and (18.97 ± 1.10)% respectively. The above apoptosis rates was much higher than that of control group (p < 0.05) and they were dose-dependent. In comparison between DFO + ADM group and DFO group, there was no significant difference (p > 0.05). Expression rate of BAX/BCL-2 increased. The levels of MDR1 mRNA reduced. Furthermore, expression of P-gp also decreased in K562/A02 cells. It is concluded that iron increase can promote K562/A02 cells growth and inhibit their apoptosis. Otherwise, iron-deprivation can induce K562/A02 cells apoptosis. DFO disturbs the iron metabolism and inhibits DNA synthesis of K562/A02 cells. This action of DFO may enhance the susceptibility of K562/A02 cells to apoptosis induced by chemotherapeutic drugs. The iron-deprivation may play a role in the treatment of leukemia with combination of DFO with other anticancer agents.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Apoptosis ; Deferoxamine ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Iron ; metabolism ; K562 Cells ; drug effects ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

Objective To investigate the morbidity of oral lesions related to human herpesvirus among a group of HIV-infected patients and its relationship with CD4.Methods A cross-sectional study was conducted in the 992 HIV-infected patients who did not receive highly active anti-retroviral therapy (HAART) in Yunnan area.Oral examination were performed by 4 dentists.Counts of CD4 + and other data were collected and statistically analyzed.Results Of the 992 cases,209 (21.1％) cases with oral lesions related to human herpesvirus were found.The virus-related diseases included herpes simplex virus (HSV) infection (10.8％,107/992),herps zoster (0.7％,7/992),oral hairy leukoplakia (OHL) (9.1％,90/992),recurrent aphthous ulcer (RAU) (9.3 ％,92/992) and Kaposi sarcoma (KS) (0.5 ％,5/992).There was a correlation between CD4 + counts and incidence of HSV infection,OHL and RAU.Oral hepes zoster had no correlation with CD4 counts.Conclusions Oral lesions associated with human herpesvirus were very common in Yunnan HIV-infected people.Among them,incidence of HSV infection,RAU and OHL was most frequently seen.

This study was aimed to investigate the reversible effect of tetrandrine, toremifene and their combination on multidrug resistance of K562/A02 cell line. The IC(50) (the concentration causing 50% inhibition of cell growth) of adriamycin (ADR) were assayed by MTT method, the expression of MDR1 mRNA was measured by RT-PCR, the concentration of p-glycoprotein (P-gp) and intracellular ADR were detected by flow cytometry. The results showed that the IC(50) of ADR on K562/A02 and K562 cells were 57.43 and 1.16 mg/L, respectively. The IC(50) of ADR on K562/A02 cells after treatment with tetrandrine, toremifene and both combination were 14.12, 20.74 and 9.14 mg/L respectively, but both drugs did not influence the IC(50) of ADR on K562 cells. Pretreating K562/A02 cells with toremifene (2.5 micromol/L), tetrandrine (1 micromol/L) or both for 72 hours partially restored the sensitivity of K562/A02 cells to ADR. Tetrandrine and toremifene (alone or combination) elevated the ADR concentration in K562/A02, down regulated the expressions of P-gp and MDR1 mRNA. It is concluded that multidrug resistance of K562/A02 cells can be partially reversed by tetrandrine or toremifene, the combination of both drugs shows a higher synergistic reversal effect.
Antineoplastic Agents, Hormonal ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Benzylisoquinolines ; pharmacology ; Doxorubicin ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drug Synergism ; Humans ; K562 Cells ; Toremifene ; pharmacology

OBJECTIVETo comparatively analyze the medical records of patients with limb fractures as well as rescue strategy in Wenchuan and Yushu earthquakes so as to provide references for post-earthquake rescue.

METHODSWe retrospectively investigated 944 patients sustaining limb fractures, including 891 in Wenchuan earthquake and 53 in Yushu earthquake, who were admitted to West China Hospital (WCH) of Sichuan University.

RESULTSIn Wenchuan earthquake, WCH met its three peaks of limb fracture patients influx, on post-earthquake day (PED) 2, 8 and 14 respectively. Between PED 3-14, 585 patients were transferred from WCH to other hospitals outside the Sichuan Province. In Yushu earthquake, the maximum influx of limb fracture patients happened on PED 3, and no one was shifted to other hospitals. Both in Wenchuan and Yushu earthquakes, most limb fractures were caused by blunt strike and crush/burying. In Wenchuan earthquake, there were 396 (396/942, 42.0%) open limb fractures, including 28 Gustilo I, 201 Gustilo II and 167 Gustilo III injuries. But in Yushu earthquake, the incidence of open limb fracture was much lower (6/61, 9.8%). The percent of patients with acute complications in Wenchuan earthquake (167/891, 18.7%) was much higher than that in Yushu earthquake (5/53, 3.8%). In Wenchuan earthquake rescue, 1 018 surgeries were done, composed of debridement in 376, internal fixation in 283, external fixation in 119, and vacuum sealing drainage in 117, etc. While among the 64 surgeries in Yushu earthquake rescue, the internal fixation for limb fracture was mostly adopted. All patients received proper treatment and survived except one who died due to multiple organs failure in Wenchuan earthquake.

CONCLUSIONProvision of suitable and sufficient medical care in a catastrophe can only be achieved by construction of sophisticated national disaster medical system, prediction of the injury types and number of injuries, and confirmation of participating hospitals?exact role. Based on the valuable rescue experiences after Wenchuan earthquake, the rescue was faster, more orderly and effective in Yushu earthquake. Nevertheless, there is still a long way to go in the development of a stronger emergent response to the disasters.

Adult ; Aged ; China ; epidemiology ; Earthquakes ; Extremities ; injuries ; Female ; Fractures, Bone ; epidemiology ; therapy ; Hospitals, Teaching ; Humans ; Male ; Middle Aged ; Retrospective Studies