BACKGROUNDReactive oxygen species (ROS) may play both physiological and pathophysiological roles. Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant response element (ARE)-mediated genes expression and coordinates induction of chemoprotective proteins in response to physical and chemical stresses. The exact role of Nrf2 in cellular responses to different levels of oxidative stresses remains unknown.

METHODSRat pulmonary microvascular endothelial cells were cultured and treated with 0 mmol/L, 0.125 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L hydrogen peroxide solution for 2 hours. Nrf2 gene expression was assayed by reverse transcription-PCR, Nrf2-ARE binding activity was assayed with electrophoretic mobility shift assay (EMSA), and localization of Nrf2 was detected with immunohistochemistry.

RESULTSLow and moderate (0.125 mmol/L, 0.25 mmol/L and 0.5 mmol/L) doses hydrogen peroxide exposure of rat pulmonary microvascular endothelial cells led to the nuclear accumulation of Nrf2, increased activity of transcription regulation and up-regulation of ARE-medicated gene expression. In contrast, high doses of hydrogen peroxide (1 mmol/L, 2 mmol/L) exposure of the cells led to the nuclear exclusion of Nrf2, decreased activity transcription regulation and down-regulation of ARE-mediated gene expression.

CONCLUSIONLow and moderate doses of hydrogen peroxide play protective roles by increasing transcription activity of Nrf2, whereas high- dose hydrogen peroxide plays a deleterious role by decreasing transcription activity of Nrf2.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Cells, Cultured ; Electrophoretic Mobility Shift Assay ; Gene Expression ; drug effects ; Hydrogen Peroxide ; pharmacology ; Immunohistochemistry ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo study the role of apoptosis and the expression of apoptosis-related genes Fas ligand (FasL), Fas, caspase-3 and caspase-8 in an animal model of non-alcoholic steatohepatitis (NASH).

METHODSAn experimental progressive NASH model was established by feeding male C57BL6/J mice with a high fat, methionine-choline deficient (MCD-) diet for two days, five days, ten days, three weeks and eight weeks. Control mice were fed methionine-choline supplemented (MCD+) diet. Hepatic steatosis, inflammation and fibrosis were graded by examining their H and E stained liver sections. Hepatocyte apoptosis was detected by TUNEL assay. Expressions of mRNA and protein of FasL, Fas and caspase-8 were performed by quantitative real time RT-PCR and Western blot. Caspase-3 activity assay was conducted using ApoAlert caspase-3 assay kit.

RESULTSIn MCD- mice, minimal hepatic steatosis was observed at day 5, and by day 10, mild steatosis with inflammatory infiltration was found. Severe steatohepatitis was noted at week 3, and fibrosis at week 8. TUNEL assay showed that apoptotic index in MCD- group was higher than that in MCD+ group at week 3 (15.59%+/-4.87% vs 5.17%+/-3.19%, P less than 0.05) and at week 8 (11.29%+/-3.22% vs 5.41%+/-1.54%, P less than 0.05). Compared to MCD+ group, the expression of FasL was dramatically increased on day 10 and in week 3 in MCD- mice both at the mRNA and protein levels (P less than 0.05 and P less than 0.01). Expression of Fas mRNA was up-regulated in weeks 3 and 8 (P less than 0.01), and expression of Fas in protein level was higher at week 8 (P less than 0.01) in MCD- group. Expression of caspase-8 significantly increased at the mRNA level at week 3 and week 8 (P less than 0.01 and P less than 0.05 respectively) and at the protein level at week 8 (P less than 0.05) in MCD- group. In all of the time points except for day 5, caspase-3 activities were significantly more enhanced in MCD- group than that in MCD+ group (P less than 0.05).

CONCLUSIONSIn our experimental NASH model, hepatic apoptosis was frequently detected. Increased apoptosis was probably attributable to up-regulation of apoptosis-related genes, such as FasL/Fas system, and activation of the caspase pathway. These changes may provoke hepatic apoptosis and the development of inflammation and fibrosis.

Animals ; Apoptosis ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Fas Ligand Protein ; metabolism ; Fatty Liver ; genetics ; metabolism ; pathology ; Hepatocytes ; metabolism ; Liver ; pathology ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVETo discuss the safety line to avoid the post-hepatectomy hepatic insufficiency by combining indocyanine green test by pulse dye-densitometry (PDD-ICG) and standard remnant liver volume (SRLV).

METHODSSeventy-five hepatic cancer patients undergone hepatectomy from March 2007 to February 2008 were included. According to the liver function decompensatory grades after operation, the relationship between ICG retention rate at 15 min (ICGR15) and standard remnant liver volume by linear regression were analyzed.

RESULTSThere were 60 cases with slight hepatic insufficiency, 12 cases with moderate hepatic insufficiency, and 3 cases with severe hepatic insufficiency. There were no difference in age [(50 +/- 13) years old and (53 +/- 9) years old], prothrombin time [(13.6 +/- 1.0) s and (13.5 +/- 1.0) s], international normalized ratio (1.09 +/- 0.10 and 1.06 +/- 0.10) between slight hepatic insufficiency group and moderate and severe hepatic insufficiency group (P > 0.05). And there were difference in K value (0.20 +/- 0.04 and 0.17 +/- 0.03), ICGR15 (6 +/- 4 and 9 +/- 4), SRLV [(545 +/- 93) ml and (398 +/- 82) ml] between two groups (P < 0.05). Compared ICG test and standard remnant liver volume of the patients with moderate hepatic insufficiency after operation, the liner relationship was found (R = 0.640, P = 0.025), and the regression equation was: standard remnant liver volume (ml/m(2)) = 1594.6 x ICGR15 + 265.

CONCLUSIONSPDD-ICG test and standard remnant liver volume are effective to estimate hepatic function reserve of patient undergone hepatectomy.

Adult ; Female ; Hepatectomy ; methods ; Hepatic Insufficiency ; etiology ; Humans ; Indocyanine Green ; pharmacokinetics ; Liver ; pathology ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Postoperative Complications ; etiology

China ; epidemiology ; Cross-Sectional Studies ; Female ; Hospitalization ; Humans ; Infusions, Intravenous ; statistics & numerical data ; Male

0.05). Conclusion The labeling of iTRAQ in HK-2 cells is successful with favourable reproducibi-lity,which lays a foundation for the further research of proteomics in renal diseases.

China ; epidemiology ; Cross Infection ; epidemiology ; Drug Resistance, Fungal ; Female ; Hospitalization ; Humans ; Male ; Microbial Sensitivity Tests ; Mycoses ; epidemiology ; Prevalence ; Respiratory Tract Infections ; microbiology ; Sentinel Surveillance

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.
Clinical Trials as Topic ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; economics ; therapeutic use ; Herbal Medicine ; economics ; legislation & jurisprudence ; Humans ; Patents as Topic ; Product Surveillance, Postmarketing ; Quality Control

Objective To investigate the characteristics about the prevalence of thyroid nodules detected on color Doppler uhrasonography(US) in people residing in Dalian City who undergo regular physical examinations, as well as its relative factors. Methods All thyroid sonographic and questionair procedures were performed in the 6020 people above 18-year-old living in the four districts of Dalian City for at least 5 years, who were examined at the department of health medical center of Dalian Municipal Central Hospital from May 2006 to March 2007. Urinary iodine concentration was measured in 2039 healthy adults selected by age layers in our study population. Moreover, urinary iodine concentrations were determined in 220 children aged 8-10 years old who were randomly chosen from four communities (55 children per elementary school from each community). The analysis of logistic regression was conducted for the risk factors linked to thyroid nodules. Results The prevalence of thyroid nodules in the 6020 adults was 38.5%(2319/6020), in which nodules sized between 0.3 and up to 0.5 cm were found in 17.1% (1030/6020), and those above 0.5 cm in 21.4% (1289/6020). Ultrsonography revealed solitary nodules in 17.2% (1036/6020), multinodular goiter in 21.3% (1283/6020). Fifty-four point nine percent (1272/2319) thyroid nodules showed solid internal echographic structures, 30.2%(701/2319) mixed and 14.9%(346/2319). The thyroid nodule detected rate in female individuals was 46.1% (1102/2393), among whom multinodular goiter [59.1% (651/1102)] was more than solitary nodules[40.9(451/1102)] in female; while only 33.6%(1217/3627) of male were detected to have thyroid nodule, there was a difference between the genders (χ2=95,079,P<0.01). The mediam urinary iodine concentration(MUI) was 184.32 μg/L in children and 216.75 μg/L in the health adults, moreover, it was 216.55 μg/L and 217.00 μg/L in the people with thyroid nodules and those without nodules without a significant difference (P>0.05). The rate of thyroid nodules gradually increased with age(χ2=344.998, P<0.01). The occurance of thyroid nodules was significant associated with gender and age(P<0.01). Conclusions The nutritional iodine intake in the four communities of Dalian City are adequate. The prevalence of thyroid incidentalomas is relatively high in this group of people receiving medical examination.

Hallux valgus is a common disorder of the forefeet,and its diagnosis and treatment have always drawn the attention of the practitioners.This article introduced the minimally-invasive diagnosis and treatment system for hallux valgus of integrated traditional Chinese and western medicine,which was established by Professor WEN Jian-Min after more than 40 years of in-depth clinical practice and research based on the theory of yin-yang balance and theory of tendons and bones in traditional Chinese medicine(TCM)and through the combination of modern surgical experience.The minimally-invasive diagnosis and treatment system for hallux valgus embodies the principles of balancing yin and yang,laying equal stress on tendons and bones,unifying the fixation and functional exercises,and treating the fractures and the whole body simultaneously,and includes the key technologies such as minimally-invasive osteotomy for the first metatarsal bone,curtain-wrapped external fixation,perioperative Chinese medicine therapy based on syndrome differentiation,and rehabilitation and nursing of TCM.The system will provide a systematic guide for the standardized minimally-invasive treatment of hallux valgus,and will supply an important approach to the treatment of other orthopedic diseases with integrated traditional Chinese and western medicine.The minimally-invasive diagnosis and treatment system for hallux valgus reflects the scientific research achievements and clinical experience of Professor WEN Jian-Min,which exerts high significance of reference and application value.

Objective::To observe the effect of realgar nanoparticles (a representative drug in toxin eliminating therapeutics) targeting hypoxia-inducible factors (HIF), which act as effector molecules on metabolic reprogramming of lung cancer stem cells, and to explore the effect mechanism of lung cancer stem cells and metabolic reprogramming in the process of lung cancer metastasis, so as to verify the effectiveness of toxin eliminating therapeutics in the prevention and treatment of lung cancer metastasis. Method::Lung cancer A549 cells were cultured in vitro, and lung cancer stem cells were then identified and selected. The stem cells were divided into blank control group, cisplatin group (5 mg·L^-1), realgar nanoparticles low, medium and high dose groups (100, 200, 400 mg·L^-1). After intervention, glucose oxidase method was used to detect the effect of realgar nanoparticles on the glucose metabolism of lung cancer stem cells, real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of hypoxia-inducible factors-1α (HIF-1α), C-myc and p53, while Western blot was used to detect the expression of related proteins HIF-1α, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and enzyme linked immunosorbent assay (ELISA) was used to detect the glucose transporter 1 (GLUT1), pyruvate dehydrogenase kinase 1 (PDK1), pyruvate kinase M (PKM), phosphofructokinase(PFK), pyruvate dehydrogenase (PDH) and lactic dehydrogenase (LDH) expression. Result::As compared with the blank control group, realgar nanoparticles can reduce the glucose consumption of lung cancer stem cells, and the glucose consumption was reduced with the increase of dose in a time-and dose-dependent manner (P<0.01). Realgar nanoparticles can inhibit the mRNA expression of HIF-1α, a key factor in metabolic reprogramming of lung cancer stem cells (P<0.05, P<0.01), down-regulated C-myc mRNA and up-regulated the p53 mRNA expression (P<0.05, P<0.01), down-regulated protein expressions of PI3K, Akt, mTOR(P<0.05, P<0.01), and inhibited the expression of related enzymes GLUT1, PDK1, PFK, PKM, PDH, and LDH levels (P<0.05, P<0.01). With the increase of dose, the regulation and control ability of realgar nanoparticles gradually increased. Conclusion::Toxin eliminating therapeutics can drive the metabolic reprogramming of lung cancer stem cells by targeting HIF effector molecule, and then inhibit the invasion and metastasis of lung cancer.