OBJECTIVETo study the clinical and pathological features of drug-induced liver injury (DILI).

METHODSLiver specimens were obtained through needle biopsies from 100 patients with DILI. The histological preparations of the specimens were stained with haematoxylin eosin, several histochemistry methods, and immunohistochemistry stains. The pathological changes of the livers were analyzed together with the patients's clinical data. The patients were divided into two groups, an acute DILI group (n=39) and a chronic DILI group (n=61), based on their clinical courses and histological changes in their livers. In the chronic DILI group, the clinical courses were longer than 6 months and/or fibrosis or cirrhosis occurred in their liver tissues.

RESULTSAmong our cases the leading cause of DILI was Chinese herb medicine, accounting for 21% of the 100 cases; steroids induced cases were 11% of the total. 78% of the patients presented elevated serum transaminases and/or jaundice. The degree of transaminases elevation and the frequency of jaundice happening in the acute group were significantly higher than those in the chronic group (P less than 0.05). The histopathological liver changes in these DILI cases included: (1) necrosis commonly occurred in acinar zone 3, (2) abundant neutrophil and/or eosinophil infiltrations, (3) hepatocytic and/or canalicular cholestasis with little or no inflammation, (4) microvesicular steatosis mixed with macrovesicular steatosis, and (5) presentation of epitheloid cell granuloma. There were no significant differences in liver histopathology between the acute and the chronic DILI groups, except that the fibrosis and the ductular proliferation were different.

CONCLUSIONDILI has become a notable liver disease in mainland China, and the use of Chinese herbal medicine must be improved, standardized and regulated more closely.

Adolescent ; Adult ; Aged ; Chemical and Drug Induced Liver Injury ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Young Adult

OBJECTIVETo explore whether the cellular apoptosis susceptibility (CAS) protein could serve as a pathologic marker for HCC diagnosis and the roles of CAS expression in HBV infection associated HCC.

METHODSThe expression of CAS protein in HCC and its paracarcinoma tissues, non-tumor liver cirrhosis and hepatitis tissues were detected by immunohistochemistry. Meanwhile, HBsAg, HBcAg and HBV DNA in HCC tissues with HBV infection were examined by immunohistochemistry and in situ hybridization respectively.

RESULTSThe expression of CAS protein was significantly higher in HCC than in its paracarcinomas tissues (P < 0.01), and higher in paracarcinomas tissues than in non-tumor liver cirrhosis and hepatitis tissues (P < 0.01). Poorly differentiated tumors immunochemically stained stronger than moderately or well differentiated (P < 0.01). CAS protein expression was significantly higher in HBV-infected HCC tissues than that of in non-HBV infection (P < 0.01). Meanwhile, in HBV-infected HCC tissues, the staining intensity score of CAS protein in HBV DNA positive HCC tissues was significantly higher than HBV DNA negative tissues (P < 0.05).

CONCLUSIONSHigher expression of CAS protein is found in HCC tissues,and the intensity of CAS protein expression is related closely to tumor differentiation. We suggested that CAS protein might serve as a marker for HCC diagnosis and differentiation estimation, and deduced that CAS might play an important role in the initiation of HBV infection associated HCC through upregulating expression of CAS.

Adult ; Aged ; Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; virology ; Cellular Apoptosis Susceptibility Protein ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Hepatitis B Core Antigens ; genetics ; metabolism ; Hepatitis B Surface Antigens ; genetics ; metabolism ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; virology ; Male ; Middle Aged

OBJECTIVEChinese jianpi herbal recipe Weichangan (WCA) could increase the survival rate of advanced gastric cancer. This study was designed to investigate the molecular mechanism of WCA in treatment of gastric cancer by cDNA array, real-time quantitative PCR and immunohistochemical technique.

METHODA human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mouse was used as the animal model. The mice were divided into 3 groups, one control and the two representing experimental conditions. Animals in the two experimental groups received either WCA over a 34-day period or 5-fluorouracil (5-FU) over 6-day period starting at 8th day after grafting. Control animals received saline on an identical schedule. Animals were killed 41 days after being grafted. To assess the effect of therapy tumor weight was determined by a electron balance immediately after the animals killed. SP immunohistochemical method was used to detect the expression of proliferating cell nuclear antigen (PCNA) in xenografts. For detection of apoptotic cells, apoptotic indices (AI) were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. SP method was also used to detect the expression of cleaved Caspase-3. The expression profiles in paired WCA treated gastric cancer samples and the N. S. control samples were studied by using a cDNA array representing 14, 181 cDNA clusters. The alterations in gene expression levels were confirmed by real-time quantitative PCR. SP method was used to detect the expression of Phospho-Stat3 (Tyr705) and bcl-2.

RESULTWhen compared with controls, tumor growth was significantly inhibited by treatment with the WCA or 5-FU (P < 0.01, respectively). The average of tumor inhibitory rate in WCA group was (44.32 +/- 5.67)% and 5-FU (47.04 +/- 11.33)%. The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group respectively. AI of human gastric cancer xenografts in nude mice was significantly increased to (9.72 +/- 4.51)% using TUNEL method in WCA group compared with the controls (2.45 +/- 1.37)%. 5-FU group was also found a significantly increased AI compared with the controls. The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively. There were 45 different expression ESTs among the control sample pool and WCA sample pool. There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated. These 45 ESTs contains 35 cloned genes and 11 unknown ESTs. By using Real-time Quantitative PCR, the expression level of Stat3 (2(-deltadeltaCT) = 0.16) , RIPX (2(-deltadeltaCT) = 0.18), ROD1 (2(-deltadeltaCT) = 0.23) and bcl-2 (2 (-deltadeltaCT) = 0.10) was lower in WCA group than that in control group respectively. The expression of Phospho-Stat3 (Tyr705) and bcl-2 in WCA group and 5-FU group was significantly decreased compared with the control group respectively.

CONCLUSIONChinese jianpi herbal recipe WCA could inhibit gastric cancer cell SGC-7901 growth in vivo. WCA could induce gastric cancer cell apoptosis and suppress proliferation. Its mechanisms might be involved in the down-regulation of Stat3, RIPX, ROD1 and bcl-2 gene.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Animals ; Antimetabolites, Antineoplastic ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Expressed Sequence Tags ; Fluorouracil ; pharmacology ; therapeutic use ; Gene Expression Profiling ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nerve Tissue Proteins ; metabolism ; Plants, Medicinal ; chemistry ; Polypyrimidine Tract-Binding Protein ; Proliferating Cell Nuclear Antigen ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA-Binding Proteins ; metabolism ; STAT3 Transcription Factor ; metabolism ; Stomach Neoplasms ; drug therapy ; genetics ; pathology ; Xenograft Model Antitumor Assays ; methods

Objective To establish information management systems of drinking water defluoridation project in water-related endemic fluorosis areas and investigate the status of drinking water defluoridation project in Liaoning, provide the basis for the development of control measures. Methods Global positioning systems (GPS)and geographic information systems(GIS) were used in the study in August 2006 - July 2008. Water defluoridation projects of 1234 in 48 counties(cities, districts) in drinking water type of fluorosis areas were positioned. Latitude and longitude, water samples, water fluoride content were collected or tested. GIS was used to establish information management system of water defluoridation projects. Results We have established information management system for the facilities of decreasing water fluorine in drinking water type of endemic fluorosis regions in Liaoning. One thousand two hundred and thirty four defluoridation facilities distributed in east longitude between 39.39° - 43.37°,north latitude between 119.25° - 125.50°, and altitude between - 6.60 and 801.14 meter in 48 endemic fluorosis counties in 13 cities. Nine hundred and twenty seven facilities for decreasing fluorine were able to supply water regularly, accounting for 75.1% of investigated projects;29 facilities was .not yet completely rebuilt, accounting for 2.4%;278 facilities(supply water for 344 villages) were out of order or discarded for 22.5% of investigated projects.Water fluorine contents of 63 facilities were greater than 1.2 mg/L, accounting for 6.8% of investigation project.Facilities working regularly and water fluorine was in accord with hygienic standard for drinking water facilities were 70.0%. Conclusions The establishment of Liaoning province defluoridation project information management system in the whole province of drinking water type of fluorosis areas provides scientific basis for accurate decision-making on prevention and control of the disease.

OBJECTIVETo explore the relationship between the changes of trace elements and lymphatic metastasis in gastric carcinoma.

METHODSTrace elements including Fe, Mg, Mn, Ca, Cu, Zn, Se were measured in primary gastric carcinoma and regional lymph nodes from 40 patients with gastric carcinoma, and compared among the primary tumor, metastatic, and non-metastatic nodes.

RESULTSThere were no significant differences in the contents of Fe, Mg, Mn and Ca among primary gastric tumors, regional lymph nodes with or without metastasis (P=0.372 - 0.741, P > 005), and no significant differences in the contents of all 7 trace elements between primary tumors and metastatic lymph nodes (P=0.15 - 0.59, P > 005). Compared with metastatic lymph nodes, the contents of Zn, Se significantly decreased, while Cu and Cu/Zn significantly increased (P=0.001 - 0.009, P< 0.01) in non-metastatic lymph nodes. The content of Zn in N2 positive lymph nodes was significant lower than that in N1 positive nodes (P=0.027). There were no significant difference in the contents of all 7 elements between intestinal type and diffuse type (P=0.149 - 0.758, P > 0.05).

CONCLUSIONSLymphatic metastasis of gastric cancer is concomitant with the changes of trace elements, and the changes of Zn, Cu, Se may be related with lymphatic metastasis.

Adult ; Aged ; Female ; Humans ; Lymph Nodes ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Stomach Neoplasms ; metabolism ; pathology ; Trace Elements ; metabolism

OBJECTIVETo study eleven organophosphorus insecticides residuals in four kinds of Chinese crude drugs.

METHODThe organophosphorus insecticides were extracted with dichloromethane and cleaned-up with a mixture of Celite 545-activated carbon. The extracts were analyzed by gas chromatography equipped with a flame photometric detector (FPD).

RESULTAnalysis of fortified Chinese crude drug showed that the average recoveries ranged from 77.5% -112.3% at three different levels, the RSDs were below 10% (n = 4). Trace organophosphorous pesticide residues were found in samples of Rhizoma Atractylodis Macrocephalae and Flos Chrysanthemi.

CONCLUSIONA method was established for determination multi-residues in Rhizma Atractylodis Macrocephalae, Radix Curcumae, Bulbus Fritillariae Thunbergii and Flos Chrysanthemi. It provides a method for the risk assessment of organophosphorous pesticide in Chinese crude drugs.

Atractylodes ; chemistry ; Chromatography, Gas ; Chrysanthemum ; chemistry ; Curcuma ; chemistry ; Drug Contamination ; Drugs, Chinese Herbal ; chemistry ; Fritillaria ; chemistry ; Organophosphorus Compounds ; analysis ; Pesticide Residues ; analysis ; Plants, Medicinal ; chemistry

UNLABELLEDTo study the androgen dependence of the neurotransmitter, calcitonin gene-related peptide (CGRP) in rat penis.

METHODSForty-four Sprague-Dawley rats were randomly divided into Group A (intact controls), Group B (castrated) and Group C (gavaged with finasteride 4.5 mg.kg(-1).day(-1)). Four and ten weeks later respectively, half of rats in each group were anaesthetized. Blood samples were taken for the measurement of serum testosterone and dihydrotestosterone (DHT) by means of radioimmunoassay. Penile samples were harvested for the investigation of calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers with immunohistochemistry. The computer-assisted imaging analysis system was applied to calculate the area proportion of the CGRP-positive nerve fibers (CGRP-PNF) in each group.

RESULTS1) Both 4 and 10 weeks later, testosterone and DHT levels in Group B decreased significantly compared with those in Group A, (P <0.05, P <0.01, respectively); DHT level in Group C was also significantly decreased in comparison with that in Group A for both 4- and 10- week animals (P <0.05); 2) There was no significant differences in area proportion of CGRP-PNF among Groups A, B and C 4 weeks after treatments (P >0.05); However, 10 weeks later, the proportion of CGRP-PNF in Groups B and C was significantly less than that in Group A (P <0.01); 3) The proportion of CGRP-PNF of 4-week animals in Groups B and C was significantly higher than that of 10-week animals (P <0.05).

CONCLUSIONThe expression of neurotransmitter, CGRP may depend on androgens, including testosterone and DHT in rat penis.

Androgens ; metabolism ; Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Dihydrotestosterone ; blood ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Penis ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

OBJECTIVETo study the effect of maternal nutrition status on child growth in China.

METHODSThe study was performed using data from 2002 China Nutrition Health Survey in which data were collected through stratified multi-stage cluster samples in 31 provinces, autonomous regions, and municipalities. Accroding to the height of women aged 18-44 y was 156.4 cm, the data on mother and children' weight and height/length (n = 1380) were analyzed.

RESULTSThe findings suggest child's length (age 2) were significantly correlated with maternal heights (P < 0.0001). The mean length in children born to mothers with a height below 156.4 cm was 2.4 cm less than those in children born to mothers with a height above 156.4 cm. The prevalence of stunting in children at age 2 born to mothers with a height below 156 cm was 2.07 times of that in children born to mothers with a height above 156 cm. Therefore, the risk for stunting in children at 2 is lower in children born to mothers with greater height.

CONCLUSIONThe maternal nutrition status could have a significant influence on children physical development.

Adolescent ; Adult ; Body Height ; Child ; Child Development ; Child, Preschool ; China ; Cross-Sectional Studies ; Female ; Humans ; Maternal Nutritional Physiological Phenomena ; Pregnancy ; Young Adult

OBJECTIVETo study the effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of fetal rats and to explore the relationship between TCDD-induced abnormal development in rats and the expression and the methylation of insulin-like growth factor 2 gene (Igf2).

METHODSA single dose of 10 microg/kg TCDD was given to gestation day (GD) 10 pregnant rats by gavage. On GD20, the fetuses were taken out and examined. The crown-rump length, the body weight and the placental weight were measured. The expression of Igf2 in liver was detected by real-time quantitative reverse transcription (RT-PCR) and Western blot. The methylation of Igf2 differentially methylated regions (DMRs) in liver was analyzed by a methylation-sensitive restriction enzyme Hpa II PCR assay and a bisulfite-modified DNA sequencing procedure.

RESULTSIn the treatment group, 12.2% of the fetuses were either dead or absorbed, and 11.6% of them were malformed. For the live fetuses, their crown-rump length, body weight and placental weight were significantly lower than those of the control group. The relative amount of Igf2 mRNA in the treated livers and the control livers was 0.77 +/- 0.11 and 0.27+/- 0.15, respectively. The number was significantly higher in the treatment group than in the control group (P < 0.01). Western blot also showed a remarkable up regulation of Igf2 protein in liver after treatment. The two groups showed no difference in the methylation status of Igf2 DMR1 in liver. The DMR2 Igf2 was significantly hypomethylated in the treated livers than in the control livers.

CONCLUSIONExposure to TCDD in pregnancy can lead fetal rats to death, absorption, malformation and intrauterine growth retardation (IUGR). The TCDD led abnormal development in rats may be associated with the hypomethylated DMR2 of Igf2 and the up regulation of Igf2 in liver.

Animals ; Blotting, Western ; DNA Methylation ; Female ; Fetal Growth Retardation ; chemically induced ; genetics ; metabolism ; Gene Expression ; drug effects ; Insulin-Like Growth Factor II ; genetics ; metabolism ; Polychlorinated Dibenzodioxins ; toxicity ; Pregnancy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUND: Important extracellular matrixes are reduced with the prolongation of duration of cyclic pressure in the endplate of the intervertebral disc. Meanwhile, the expression of Wnt-5a gene is significantly decreased. There is an important relationship between Wnt-5a gene and intervertebral disc degeneration (IDD). OBJECTIVE: To investigate the expression of Wnt-5a gene under cyclic pressure in a rabbit model of IDD and to explore its role in IDD progress. METHODS: Lumbar intervertebral discs were removed from the 6-month-old New Zealand white rabbits to prepare IDD models and were then randomly divided into experimental (cyclic pressure ) and control (no intervention) groups. The morphological changes of intervertebral discs were observed by hematoxylin-eosin staining and safranin O-fast green staining. The mRNA expression levels of proteoglycan, collagen type Ⅱ, and Wnt-5a were detected by real-time PCR. The protein expression level of Wnt-5a was detected by western blot assay. RESULTS AND CONCLUSION: The morphology of intervertebral discs cultured for 7 days in the experimental and control groups showed a certain change, but was still intact; expression levels of aggrecan, type Ⅱ collagen, Wnt-5a showed differences from the intervertebral discs cultured for 0 day. On day 14, the damage to the histomorphology was severer in the experimental group than the 0-day control group. The mRNA expression levels of proteoglycan, collagen type Ⅱ, and Wnt-5a were decreased in both groups, especially the experimental group, at 7 and14 days. The mRNA and protein expression levels of Wnt-5a revealed the same change trend with time. To conclude, regulation of Wnt-5a expression may alter the process of endplate cartilage degeneration, and thus providing new ideas for the prevention and treatment of IDD.