OBJECTIVETo investigate the clinical manifestation of patients with renal injury induced by chronic mercury intoxication and the application of the diagnostic criteria of occupational mercury poisoning.

METHODSThe clinical data of 8 patients with chronic occupational mercury intoxication were analysed and evaluated.

RESULTSAll the observed clinical signs of chronic mercury intoxication correspond with the items of the diagnostic criteria of occupational mercury poisoning. The increasing beta2-MG was one of the clinical manifestations of renal injury induced by chronical mercury intoxication. The renal injury obviously was dose-dependent and reversible.

CONCLUSIONSThe national diagnostic criteria of occupational mercury poisoning is practically valuable. The renal injury induced by chronic mercury intoxication should not be neglected.

Adult ; Female ; Humans ; Male ; Mercury Poisoning ; diagnosis ; Middle Aged ; Occupational Diseases ; diagnosis ; Reference Standards

OBJECTIVETo evaluate the impact of preoperative three-dimensional visualization and virtual liver surgery planning on hepatic resection.

METHODSAll relevant structures (livers, portal vein, hepatic veins, and tumors) were extracted from multislice CT scans of 142 cases treated from May 2007 to May 2009. By the liver surgery planning system software Liv 1.0, reconstruction and image analysis of the relevant structures was performed and virtual resections of liver were carried out. Data were correlated to intraoperative findings.

RESULTS(1) Three-dimensional visualization revealed the spatial relationship of tumors to the intrahepatic vascular system, thus giving impressions how the neoplasms were situated. Virtual tumor resections corresponded to the intraoperative findings. (2) With the planning, an intended resection could be performed virtually and optimal identification of resection margins could be achieved. The ischemia and congestion territory within the remaining liver parenchyma could be calculated. Simulation resections could avoid liver parenchyma over resection and maintain a sufficient amount of liver tissue to sustain hepatic function. Virtual simulations of tumor resection were used successfully to plan of surgical procedures in the hepatic tumors. Hepatectomy was performed in 29 cases after virtual tumor resections but seemed impossible with conventional CT scan. Resection plans of 92 cases were optimized after virtual resections. (3) The mean liver volume of patients with primary hepatocellular carcinoma measured by the software and the real resected was (477 +/- 223) ml and (451 +/- 209) ml respectively. Comparison by means of linear regression analysis between volume measurement on the software and the real resected showed a nearly ideal correlation coefficient (R = 0.922, P < 0.01). The mean error was 6.1%.

CONCLUSIONSThe three-dimensional tumor visualization and virtual simulation of tumor resections of the software Liv 1.0 provide an important reference for a valuable planning of complex hepatic resections. It is not only benefit to improve the predictability and security of hepatectomy but also helpful to improve the success rate of complex hepatic resections.

Adult ; Aged ; Computer Simulation ; Female ; Hepatectomy ; methods ; Humans ; Imaging, Three-Dimensional ; Liver ; diagnostic imaging ; surgery ; Liver Neoplasms ; surgery ; Male ; Middle Aged ; Tomography, X-Ray Computed ; User-Computer Interface ; Young Adult

OBJECTIVETo analyze the effect of different hepatic vascular exclusions for massive hemorrhage in hepatectomy.

METHODSThe clinical data of 2238 cases with hepatectomy treated from January 1995 to August 2009 was analyzed retrospectively in the cause of massive hemorrhage (blood loss ≥ 1000 ml), blood loss during liver resection and massive hemorrhage incidence with different methods of hepatic vascular exclusion.

RESULTSAmong 2238 cases received hepatectomy, 215 cases (9.6%) had massive hemorrhage because of portal vein tumor thrombus extraction (26.0%), extensive adhesions around the tumor (24.7%), section of liver hemorrhage (23.7%), hepatic vascular injury (15.8%), and tumor rupture (9.8%). Among 2182 cases received hepatectomy without portal vein tumor thrombus extraction, 159 cases (7.3%) had massive hemorrhage, 1257 cases (57.6%) which blood loss were less than 400 ml. Hepatectomy with different hepatic vascular exclusion methods had different blood loss and massive hemorrhage incidence.

CONCLUSIONPringle combined with clamping infrahepatic vena cava method and the liver double-hanging maneuver through the retrohepatic avascular tunnel on the right of the inferior vena cava method can reduce blood loss and massive hemorrhage incidence in hepatectomy more effectively, especially for huge liver tumor resection.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Loss, Surgical ; prevention & control ; Female ; Hepatectomy ; methods ; Humans ; Liver ; blood supply ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

The microRNA (miRNA) regulation mechanisms associated with atherosclerosis are largely undocumented. Specific selection and efficient validation of miRNA regulation pathways involved in atherosclerosis development may be better assessed by contemporary microarray platforms applying cross-verification methodology. A screening platform was established using both miRNA and genomic microarrays. Microarray analysis was then simultaneously performed on pooled atherosclerotic aortic tissues from 10 Apolipoprotein E (apoE) knockout mice (apoE-/-) and 10 healthy C57BL/6 (B6) mice. Differentiated miRNAs were screened and cross-verified against an mRNA screen database to explore integrative mRNA-miRNA regulation. Gene set enrichment analysis was conducted to describe the potential pathways regulated by these mRNA-miRNA interactions. High-throughput data analysis of miRNA and genomic microarrays of knockout and healthy control mice revealed 75 differentially expressed miRNAs in apoE-/- mice at a threshold value of 2. The six miRNAs with the greatest differentiation expression were confirmed by real-time quantitative reverse-transcription PCR (qRT-PCR) in atherosclerotic tissues. Significantly enriched pathways, such as the type 2 diabetes mellitus pathway, were observed by a gene-set enrichment analysis. The enriched molecular pathways were confirmed through qRT-PCR evaluation by observing the presence of suppressor of cytokine signaling 3 (SOCS3) and SOCS3-related miRNAs, miR-30a, miR-30e and miR-19b. Cross-verified high-throughput microarrays are optimally accurate and effective screening methods for miRNA regulation profiles associated with atherosclerosis. The identified SOCS3 pathway is a potentially valuable target for future development of targeted miRNA therapies to control atherosclerosis development and progression.
Animals ; Aorta/metabolism/pathology ; Apolipoproteins E/*deficiency/metabolism ; Atherosclerosis/genetics/pathology ; Down-Regulation/genetics ; Gene Expression Profiling ; *Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Models, Biological ; *Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/*genetics ; Suppressor of Cytokine Signaling Proteins/genetics/metabolism ; Up-Regulation/genetics

OBJECTIVETo explore the mechanism of multidrug resistance of hepatocellular carcinoma induced by hypoxia and the potential role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and multidrug resistance related genes.

METHODSHuman hepatocarcinoma cell lines HepG2 cells were exposed to hypoxia and were transfected by plasmid HIF-1 alpha/PCDNA3, respectively. The expressions of multidrug resistance gene (mdr1), multidrug resistance protein (MRP1), and lung resistance protein (LRP) gene at the mRNA and the protein levels in the above two groups were respectively analyzed by real-time fluorescent quantitative PCR and Western-blot technique.

RESULTSIn the hypoxia group, the expressions of mdr1, MRP1 and LRP were stepped up correlating to the degree of hypoxia, especially the prominent increase in the expression of MRP1. Furthermore, they were synchronous with the changes of the expression of HIF-1 alpha. Also the increased expression of mdr1, MRP1, and LRP gene was observed in transfected HepG2 cells by plasmid HIF-1 alpha/PCDNA3.

CONCLUSIONSResistance of hepatocellular carcinoma to chemotherapeutics could be induced by hypoxia. HIF-1 alpha may be critical to the upregulation of the expression of the related multidrug resistance genes induced by hypoxia. HIF-1 alpha and these related multidrug resistance genes could be potential molecular targets for reversing multidrug resistance of hepatocellular carcinoma.

Blotting, Western ; Carcinoma, Hepatocellular ; genetics ; Cell Hypoxia ; physiology ; Cell Line, Tumor ; Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Gene Expression Regulation, Neoplastic ; Genes, MDR ; genetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; biosynthesis ; genetics ; Lung Neoplasms ; genetics ; Multidrug Resistance-Associated Proteins ; biosynthesis ; genetics ; Polymerase Chain Reaction ; Transfection ; Vault Ribonucleoprotein Particles ; biosynthesis ; genetics

BACKGROUNDAccumulating evidence demonstrates that the microenvironment of the host has an important effect on the chemoresistance of tumors. We also found that the formation of intrinsic multidrug resistance is related to environmental factors that are common with tumor growth of hepatocellular carcinoma. The aim of this study was to explore the molecular mechanisms by which multidrug resistance of hepatocellular carcinoma is induced by the microenvironment. In particular, the regulation of nuclear transcription factor (hypoxia-inducible factor-1α, HIF-1α) activation in the process of multidrug resistance formation was investigated.

METHODSHepG2 cells were exposed to different microenvironmental conditions respectively, such as hypoxia, stimulation of glucose deprivation and transfection of plasmid PcDNA3/HBx. In the HepG2 cells, the expression of the related MDR proteins, HIF-1α protein expression and localization, activity of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) were detected. Specific inhibitor U0126 was used to block ERK/MAPK signal pathway, the alteration of HIF-1α and the related MDR proteins were investigated. Multivariate analysis of variance (MANOVA) repeated measures and one-way analysis of variance (ANOVA) followed by Tukey test or t-test were used to determine differences over time and effects of the treatments.

RESULTSThe above three microenvironment factors increase the expression of the related MDR proteins (including P-gp, LRP, and MRP1) and induce MDR of HepG2 cells. HIF-1α was induced at the protein and mRNA levels and the nuclear translocation was also increased. The activity of ERK/MAPK was also increased in HepG2 cells. But when ERK/MAPK pathway was inhibited, the mRNA and protein expression of MDR1, MRP1, and LRP was to some extent decreased. Inhibition of ERK/MAPK significantly reduced activated HIF-1α protein and the nuclear translocation of HIF-1α, whereas HIF-1α mRNA levels were not affected.

CONCLUSIONSThe microenvironmental factors could induce MDR of HepG2 cells by the activity of HIF-1α. The activity of HIF-1α is regulated by the ERK/MAPK pathway at the phosphorylation level. As an important nuclear transcription factor, HIF-1α controls the transcription of MDR-related genes and the synthesis of their corresponding proteins by ERK/MAPK signal pathway in HepG2 cells.

Drug Resistance, Neoplasm ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; physiology ; MAP Kinase Signaling System ; Tumor Microenvironment

OBJECTIVETo elucidate intracellular signal pathway in formation of multidrug resistance (MDR) of hepatocellular carcinoma (HCC) induced by its microenvironment, and to explore the potential role of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in this process.

METHODSActivity of ERK/MAPK was examined by Western blot technique through comparing the ratio of phosphorylation of ERK/MAPK to total ERK/MAPK protein in HepG2 cells exposed to hypoxia, low glucose or transfected by plasmid pcDNA3/HBX. After being treated by the specific ERK/MAPK pathway inhibitor U0126, Western blot technique was used to analyze the alterations of the expression of P-gp, MRP1, LRP and HIF-1alpha at protein level. RT-PCR was used to analyze the alterations of the expression of HIF-1alpha mRNA. Cellular location of HIF-1alpha protein was determined by immunocytochemistry after being treated by U0126.

RESULTSThe activations of ERK/MAPK determined by the ratio of phosphorylated ERK/MAPK to the total ERK/MAPK were increased in varying degrees in HepG2 cells respectively exposed to different microenvironment. After being treated by U0126 for 12 h, the expressions of mdr1, MRP1, LRP genes and protein in those cells were decreased to some extent. However, the gene expression of HIF-1alpha was not influenced and only its protein was decreased. HIF-1alpha protein was reversely translocated into cytoplasm from nucleus after being treated by U0126.

CONCLUSIONSERK/MAPK pathway is involved in the course of the formation of MDR of HCC induced by microenvironment.

Blotting, Western ; Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; genetics ; metabolism ; pathology ; MAP Kinase Signaling System ; physiology ; Mitogen-Activated Protein Kinases ; metabolism ; Multidrug Resistance-Associated Proteins ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo observe the association between systemic lupus erythematosus (SLE) and gene polymorphisms of OLF-1/EBF associated zinc finger protein(OAZ).

METHODSVerified single nucleotide polymorphisms (SNPs) with relatively high heterozygosity were chosen for allelic discrimination in 244 Chinese SLE pedigrees. Then transmissions of single SNP, and haplotypes were calculated by Genehunter software..OAZ mRNA level was also measured for comparing gene expression in patients of different haplotypes.

RESULTSGenotyping of five SNPs within OAZ gene introns indicated there was no preferential transmission of single SNP, and haplotype T-A-G-G for rs1344531-rs2080353-rs933564-rs1345431 showed only weak linkage with the disease (P=0.04). However, haplotypes combining SNPs and the SLE-associated D16S517 allele showed significant association with SLE susceptibility (for rs933564-d16s517 G-271bp t:non-t=93:29 P<0.000001, for rs2080353-rs933564-d16s517 A-G-271bp t:non-t=88:35 P=0.000002). The haplotype A-G-271bp-G of Rs2080353-rs933564-D16s517-rs1345431 was also transmitted to patients preferentially (P=0.0084) and it showed a tendency to affect gene expression.

CONCLUSIONSpecial polymorphism haplotype of OAZ gene is associated with Chinese SLE. OAZ may suggest a new pathway for lupus.

Asian Continental Ancestry Group ; genetics ; China ; DNA-Binding Proteins ; genetics ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; Humans ; Lupus Erythematosus, Systemic ; ethnology ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo evaluate the efficacy and safety of selective serotonin re-uptake inhibitors (SSRIs) in the treatment of premature ejaculation (PE).

METHODSFrom MEDLINE (Jan, 1950-Mar, 2008), EMBASE (Jan, 1980-Mar, 2008), The Cochrane Library (Issue 1, 2008) and CNKI (Jan, 1979-Mar, 2008), we retrieved and screened the randomized controlled trials (RCT) and randomized crossover trials (RT) as well as various related data, published and unpublished, on the treatment of PE with SSRIs. The methodological quality of the included trials was evaluated by 2 reviewers. Meta-analyses were conducted with RevMan 5.0 on the homogeneous studies.

RESULTSTotally 22 studies on 4 291 patients were included. Meta-analyses showed that after treated with sertraline, fluoxetine, paroxetine, citalopram, dapoxetine and fluvoxamine, the WMD (95% CI) values of the changes in intravaginal ejaculatory latency time (IELT) were 2.63 (1.80, 3.46), 2.21 (1.50, 2.92), 4.31 (2.71, 5.91), 3.82 (3.39, 4.25), 1.57 (1.31, 1.84) and 0.01 (0.71, 0.73) respectively; the RR (95% CI) values of the sexual satisfaction rate of the patients were 1.65 (1.12, 2.43), 2.93 (0.50, 17.31), 3.08 (2.27, 4.17), 2.48 (1.99, 3.09) and 2.93 (2.36, 3.65), and those of their partners were 1.47 (0.98, 2.21), 2.88 (0.38, 21.77), 4.81 (3.15, 7.36), 5.38 (3.75, 7.72) and 2.91 (1.09, 7.78) respectively for sertraline, fluoxetine, paroxetine, citalopram and dapoxetine.

CONCLUSIONAll the known SSRIs but fluvoxamine could prolong IELT, and some could improve the sexual satisfaction of both the patients and their partners, but their adverse effects should be noted. The moderate possibility of selection bias and publication bias in the included studies might have a negative impact on the evidence intensity of our results. We expect more reliable evidence from more randomized controlled trials.

Humans ; MEDLINE ; Male ; Randomized Controlled Trials as Topic ; Serotonin Uptake Inhibitors ; adverse effects ; therapeutic use ; Sexual Dysfunction, Physiological ; drug therapy ; Treatment Outcome

OBJECTIVETo select the optimal pregnancy time window of embryonic pig skin precursor tissue for xenotransplantation and study its ability in wound repair.

METHODSSkin precursor tissues were obtained from pig fetus of fetal age of 35, 42, 56, 70 days, and were minced into microskin and transplanted to dorsal wounds of BALB/c nude mice, then they were covered with residual skin after plastic surgery of patients or adult pig skin (white). The characteristics of growth and development were observed after transplantation. Pathological examination was performed on 6 and 12 post operation weeks respectively to observe the tissue structure and tumorigenicity.

RESULTSSkin precursor tissues from fetal pig survived and developed after transplantation, and the microskin fused. New tissue area from skin precursor tissues with fetal age of 42 days was (47 +/- 6) mm2, which was higher than that of 35 days (18 +/- 8 mm2), 56 days (31 +/- 12 mm2), 70 days (20 +/- 8 mm2, P < 0.05). The skin precursor developed into "intact skin" with hair, sebaceous glands and sweat glands, and melanocytes were also detected in epidermis. The newly-grown skin tissue included epidermal and dermal layer, and obvious dermal papillae. Teratoma was not found after transplantation in skin precursor tissue with fetal age of 56, 70 days.

CONCLUSIONFetal pig skin precursor tissue with fetal age of 56 days can be used to repair wound as xenotransplantation.

Animals ; Fetal Tissue Transplantation ; Fetus ; Gestational Age ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Skin Transplantation ; Swine ; Transplantation, Heterologous ; Wound Healing