To study the immunopathological characteristics and differential diagnosis of hepatic angiomyolipoma(AML).Methods:Thirty-six surgically resected hepatic AML were investigated clinicopathologically and immunohistochemically with 10 antibodies.Results:Hepatic AML occurred in 21 females and 15 males,with the mean age of 41.6 years(26-60 years old).The patients with AML often had no special symptoms even had large space-occupying lesions in the liver.The diameter of AML was 2.5 cm to 14 cm(mean 6.8 cm).Histologically,AML was composed of varying heterogeneous mixture of 3 tissue components:blood vessels,smooth muscle and adipose cells.Extramedullary hemopoiesis sometimes existed.According to tissue components,AML was subcategorized into mixed type(19.4%,n=7),lipomatous type(11.1%,n=4),myomatous type(66.7%,n=24),and angiomatous type(2.8%,n=1).The epithelioid smooth muscle cells were sensitive to HMB-45(100%),SMA(100%),and CD117(66.7%) staining.Conclusion:Hepatic AML often contains smooth muscle elements,which have varied morphological features and should be carefully differentiated from hepatocellular carcinoma,mesenchymal hamartoma，and tumors with rich fat or blood vessels.Immunohistochemical staining with HMB-45 and SMA are the best available markers for the diagnosis of hepatic AML.

OBJECTIVETo study the effect of Guishen Pill (GSP) on expression levels of Oct-4, MVH, and Egr-1 in mice with diminished ovarian reserve (DOR).

METHODSTotally 40 female C57BL/6J mice were randomly divided into 4 groups, the normal control group, the model group, the GSP group, and the dehydroepiandrosterone (DHEA) group, 10 in each group. Pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG), and prostaglandin F2α (PGF2α) were sequentially administrated to produce superovulation. The DOR model was established by exposing to ozone inhalation. Mice in the GSP group were intragastrically administered with GSP at 0.3 mL. Those in the DHEA group were intragastrically administered with DHEA at 0.3 mL. Equal volume of normal saline was intragastrically administered to mice in the normal control group and the model group. All mice wer treated for 21 days. Serum levels of estrogen (E2), progestogen (P), and anti-Müllerian hormone (AMH) were measured by ELISA. Changes of Oct-4, anti-AMH, and early growth response gene-1 (Egr-1) mRNA in ovaries were dtected by Real-time PCR.

RESULTSCompared with the model group, serum levels of E2, P, and AMH, as well as contents of estrogen receptor (ER), progestogen receptor (PR), MVH, and Oct-4 mRNA significantly increased in the GSP group and the DHEA group (P < 0.05).

CONCLUSIONGSP could improve expression levels of Oct-4, MVH, and Egr-1 mRNA in DOR mice and their ovarian function.

Animals ; Anti-Mullerian Hormone ; metabolism ; Dehydroepiandrosterone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Early Growth Response Protein 1 ; metabolism ; Estrogens ; Female ; Mice ; Mice, Inbred C57BL ; Octamer Transcription Factor-3 ; metabolism ; Ovarian Reserve ; Ovary ; Pregnancy ; Receptors, Estrogen ; metabolism ; Superovulation

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

Copy number aberrations (CNAs) in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma (HCC).This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients,and further screen for differentially expressed genes in outcome-related CNAs.Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels,respectively.The correlations between CNAs in 8q and outcomes were analyzed in 66 patients,with a median follow-up time of 45.0 months (range,2.6-108.6 months).One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs.Copy number gain in 8q was observed in 22 (33.3 ％) of the 66 HCC cases.The most recurrent gains (with frequencies ＞20％) were 8q13.3-21.3,8q21.3-23.3,8q23.3-24.13,8q24.13-24.3,and 8q24.3.Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival (P=0.010).Multivariate Cox analysis identified 8q24.13-24.3 gain as an independent prognostic factor for poor overall survival (HR=2.47;95％CI=1.16-5.26;P=0.019).A panel of 17 genes within the 8q24.13-24.3 region,including ATAD2,SQLE,PVT1,ASAP1,and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without.These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients,and the potential oncogenes ATAD2,SQLE,PVT1,ASAP1,and NDRG1 within the regional gain,may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.

OBJECTIVETo investigate the effect of ulinastatin on renal function and ultrastructure changes after renal ischemia-reperfusion in rats.

METHODSAcute ischemic renal injury model was established (45 min of bilateral renal ischemia and reperfusion for 24 h). Thirty Male SD rats were randomly divided into 3 groups: sham operation group (control group or group C, without renal ischemia), renal ischemia-reperfusion group (ischemia-reperfusion group or group I, without ulinastatin), renal ischemia-reperfusion and ulinastatin intravenous injection group (ulinastatin group or group U). BUN level, serum creatinine values and renal ultrastructure were measured.

RESULTSSerum creatinine (167 +/- 39) micromol/L and BUN concentration (21 +/- 7) mmol/L in group I were significantly higher than those in group U: serum creatinine (116 +/- 13) micromol/L and BUN concentration (14.1 +/- 2.6) mmol/L (P < 0.05). The renal ultrastructure was greatly injured in group I, meanwhile, it was obviously ameliorated in group U.

CONCLUSIONUlinastatin greatly improved renal function and provides remarkable protection on renal ultrastructure after ischemia-reperfusion of kidney in rats.

Animals ; Glycoproteins ; pharmacology ; Kidney ; blood supply ; drug effects ; ultrastructure ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; pathology

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Liver ; pathology ; Liver Diseases ; pathology ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Postoperative Complications ; pathology ; Young Adult

OBJECTIVETo investigate the association between tumor necrosis factor-beta (TNF-beta) gene polymorphisms and coronary heart disease (CHD).

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific primer-PCR (PCR-SSP) were used for the detection of TNF-beta genotype in 210 patients with CHD and 186 healthy controls. The serum TNF-beta levels were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe frequencies of CC, CA and AA genotypes of C804A in patients and controls were 25.7% and 37.1%, 49.5% and 45.7%, 24.8% and 17.2%, respectively; there were statistically significant differences in the distributions of the genotypes (P<0.05) and the allele frequencies (P<0.05) between the two groups; the risk of suffering from CHD in those of AA and CA genotypes was 1.704 times that in those of CC genotype (OR=1.704, 95%CI: 1.109-2.617). However, there was no significant difference in the distribution of the genotype of G252A between the patients and controls, though significant difference was seen between the subgroups of the CHD group. The serum TNF-beta and high sensitive C-reactive protein (hsCRP) levels of the patients were significantly higher than those of the controls (P<0.05); however, there were no significant differences in regard to different TNF-beta genotypes among the patients and controls respectively.

CONCLUSIONThe single nucleotide polymorphism (SNP) at position 804 in the exon 3 of TNF-beta gene is associated with CHD and the allele A may be a risk factor for CHD in Chinese. The polymorphism of G252A may not play an important role in the pathogenesis of CHD.

Aged ; Asian Continental Ancestry Group ; Coronary Disease ; genetics ; Exons ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Introns ; Lymphotoxin-alpha ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide

OBJECTIVESTo study the effects of rat endothelial progenitor cell (EPC) transplantation on hepatic fibrosis in carbon tetrachloride (CCl4) induced hepatic fibrosis rats.

METHODSHepatic fibrosis was developed in 24 healthy female SD rats by feeding them 25% CCl4/olive oil for 8 weeks. Eight of them were sacrificed at the end of the 8 weeks. The rats were subdivided into a EPCs transplanting group (n=8) and a saline control group (n=8). After the EPCs were isolated and cultured for 9 days, the cells were injected into the portal veins of the rats in the EPCs transplanting group. Four weeks later all of the rats were sacrificed. The blood biochemical parameters from the serum were examined. The degree of liver fibrosis was evaluated by reading Masson staining liver slides and by detecting the expression of a-SMA and collagen III.

RESULTSCompared with the saline control group, hepatic activity index (HAI), levels of ALT, AST and TBil in the serum were all lower in the EPCs transplanting group, but the level of Alb was higher and the expression of a-SMA and collagen III were lower. Compared with the 8 week hepatic fibrosis group, the levels of ALT, AST and TBil in the serum of the EPCs transplanting group were all lower. In the saline control group, the serum levels of ALT, AST and TBil were higher, the level of Alb was lower, and the expressions of a-SMA and Collagen III were higher.

CONCLUSIONIn hepatic fibrosis rats, transplantation of rat EPCs could minimize the hepatic fibrosis process and the injuries.

Animals ; Carbon Tetrachloride ; Endothelial Cells ; cytology ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; pathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Stem Cell Transplantation

Adolescent ; Adult ; Child ; Female ; Fracture Fixation, Intramedullary ; methods ; Humans ; Male ; Radius Fractures ; surgery

OBJECTIVETo study the features of micro satellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC).

METHODSTen high-polymorphic micro satellite markers on chromosome 4 were selected to be detected for loss of heterozygosity (LOH), micro satellite instability (MSI) and allelic imbalance (AI) in 56 HCC using PCR-simple sequence length polymorphism (PCR-SSLP) analysis.

RESULTSLOH was found in 40 of 56 HCC (71.4%) on at least 1 locus, the top two loci were D4S426 (61%), D4S1534 (53.7%). LOH on D4S406 was significantly higher in cases with positive serum HBsAg than in those with negative HBsAg. Similarly, LOH on D4S1538 occurred more frequently in patients with HBsAg negative than those with HBsAg positive [76.9% (20/26) vs 12.5% (2/16), chi2=13.999, P<0.01]. LOH on D4S426, D4S1615 and D4S165 were more frequent in poorly or moderately differentiated HCC than in well-differentiated HCC [76.7%(23/30) vs 18.2%(2/11), chi2=9.242, P<0.01; 53.8% (14/26) vs 16.7% (2/12), P<0.05; 60.7% (17/28) vs 18.2% (2/11), P<0.01]. LOH on loci D4S2921 was more frequently detected in tumors with intrahepatic metastasis than in those without [63.6% (21/33) vs 18.2% (2/11), chi2=5.132, P<0.01]. MSI was found in 8.9% (5/56) cases. AI was found in 26.8% (15/56) of all cases examined.

CONCLUSIONFrequent micro satellite alterations on chromosome 4 were existed in HCC. LOH, which represents tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis of HCC; MSI, representing mismatch repair gene pathway, arranges as the next.

Adult ; Aged ; Carcinoma, Hepatocellular ; genetics ; Chromosomes, Human, Pair 4 ; Female ; Humans ; Liver Neoplasms ; genetics ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged