The study aims to investigate the embryo-fetus development toxicity of the novel PPAR-δ agonist HS060098 on SD rats. The pregnant rats that were randomly divided into the solvent control group (1% hydroxypropyl methyl cellulose water solution) and HS060098 suspension groups (10, 30 and 100 mg x kg(-1) xd(-1)) were orally administered with HS060098 suspension or vehicle during the gestation of 6 -15 days (GD6-15). At termination (GD20), female rats were sacrificed. The pregnant females were evaluated by corpora lutea count, implantation sites, existence and death of embryos. Fetal sex, weight, externals, variations and malformations of viscus and skeleton were observed. The results show that there were no significant abnormality in maternal general conditions and fetal appearance as well as viscera, but in the 100 mg x kg(-1) x d(-1) group, the maternal weight gain decreased greatly (P < 0.01) and the skeletal ossification delayed remarkably (P < 0.01); in the 30 mg x kg(-1) xd(-1) group, the fatal and litter number of incompletely ossified sternebrae II was higher than those of the control group (P < 0.05); the skeletal malformations occurred in all dose groups, which indicate that the novel PPAR-δ agonist HS060098 had maternal toxicity and adversely effected fetal skeletal development under the experimental conditions.
Animals ; Bone and Bones ; drug effects ; Embryonic Development ; drug effects ; Female ; Fetal Weight ; PPAR delta ; agonists ; Pregnancy ; Rats ; Toxicity Tests

Objective To explore the changes of soluble tumor necrosis factor receptor type 1(sTNFR1)in children with acute virus encephalitis(VE)and its clinical significance.Methods The levels of tumor necrosis factor-?(TNF-?),sTNFR1 and neuron specific enolase(NSE)in cerebrospinal fluid were determined by enzyme-linked immunosorbent assay(ELISA)in 55 children who were admitted with VE,including 25 cases with severe VE(SVE)and 30 cases with mild VE(MVE).Fifteen cases without VE were as control group.Results The levels of TNF-?,sTNFR1 in cerebrospinal fluid in encephalitis children were significantly higher than that in control group(Pa

OBJECTIVETo study the effect of hydroxycamptothecin (HCPT) on apoptosis-inducing factor (AIF) expression and AIF translocation from mitochondria to the nucleus in human hepatocellular cancer cell SMMC-7721 during apoptosis.

METHODSAfter treatment with 80 mg/ml of HCPT, the cancer cells were stained with A0/EB to monitor their apoptosis. Their mitochondria was examined with electronmicroscopy and the AIF expression of the cells was tested by RT-PCR and Western blot. The translocation of AIF from mitochondria to the nucleus during apoptosis was analyzed by confocal microscopy.

RESULTSSMMC-7721 cells treated with HCPT showed chromatin condensation, nuclear fragmentation and mitochondria swelling. The mRNA and protein expression of AIF in treated and untreated SMMC-7721 cells were not significantly different. However, cells treated with 80 mg/ml HCPT for 6 h or 12 h showed massive translocation of AIF into the nuclei.

CONCLUSIONThese results show the important role the mitochondrial pathway of apoptosis plays in HCPT-induced tumor cell death, at least in SMMC-7721 cells.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Apoptosis Inducing Factor ; biosynthesis ; genetics ; Camptothecin ; analogs & derivatives ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Humans ; Liver Neoplasms ; pathology ; Translocation, Genetic

OBJECTIVESTo investigate the differentially expressed mitochondrial proteins in hydroxycamptothecin (HCPT)-treated SMMC-7721 cells by using quantitative proteome.

METHODSSMMC-7721 cell apoptosis was induced by HCPT and the mitochondria were isolated with a mitochondria isolation kit. Mitochondrial proteins labeled with a cleavable isotope-coded affinity tag were identified and quantified using two-dimensional liquid chromatography/tandem mass spectrometry.

RESULTSHighly purified mitochondria were obtained. Seventy-four mitochondrial proteins, which were statistically significantly altered (P less than 0.05) in HCPT-treated cells, were identified and analyzed. A total of 42 proteins were significantly down-regulated, and 32 were up-regulated in the cells that responded to apoptosis. The functions of these proteins were likely involved in cell energy metabolism, nucleic acid translation and transcription, cytoskeleton, etc.

CONCLUSIONOur results about the information of differentially expressed mitochondrial proteins in HCPT-treated cells and the control cells will help to understand the mechanism by which HCPT induces cell apoptosis. The integrated techniques we used in this study will be helpful to the investigation of subcellular quantitative proteomics.

Apoptosis ; drug effects ; Camptothecin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Humans ; Mitochondria ; metabolism ; Mitochondrial Proteins ; metabolism ; Proteome ; metabolism

OBJECTIVETo study regulation of Ca(2+)-activated K(+) channels (KCa) of mesenteric artery smooth muscle cell (SMC) from 21 old patients with essential hypertension (EH) by endothelin-1 (ET-1) and prostagl E(1) (PGE(1)).

METHODSMesenteric artery branch from EH was digested by enzyme. Patch clamp technique was used to pull cell-attached and inside-out patches on mesenteric artery SMC from EH and the normotensive patients respectively. The signal channel open probability (Po), open dwell-time (To) and close dwell-time (Tc), open channel number per patch were recorded. After adding Ca(2+) (10(-8) approximately 10(-6) mol/L), ET-1(2 approximately 8 x 10(9) mol/L) and PGE(1) (10, 20, 40, 100, 200, 400 nmol/L) to cytoplasm respectively. The parameters above were observed again.

RESULTSCompared to that of normotensive patients, the activities of KCa channels of patients with EH was higher. After adding Ca(2+) to cytoplasm,the Po of KCa channels in normotensive patients increased significantly. But it was few changes in EH group. KCa channels has dual reaction to ET-1 in normotensive patients. We have found no statistics difference when ET-1 present on KCa channels of EH cases. Whereas PGE(1) can affect KCa channels current and channels kinetic significantly in side-out patches. The Po of KCa channels increased. The To protracted and the Tc curtailed in EH.

CONCLUSIONSThe activities of KCa channels of patients with EH increased significantly. but the sensitive to Ca(2+) decreased. ET-1 were few effect to KCa channels. The PGE(1) can activated KCa channels of patients with EH.

Aged ; Alprostadil ; pharmacology ; Cells, Cultured ; Endothelin-1 ; pharmacology ; Female ; Humans ; Hypertension ; metabolism ; physiopathology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; cytology ; Middle Aged ; Muscle, Smooth ; metabolism ; physiopathology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; drug effects ; metabolism

OBJECTIVETo analyze the pathological type and clinical features of patients with lymphoma cell leukemia (LML).

METHODSAccording to the 2008 WHO classification of tumors of hematopoietic and lymphoid tissue, the pathological type and clinical features of 127 LML cases were analyzed retrospectively.

RESULTSThere were 15 kinds of NHL developed LML. The incidence in frequent order of them was B-lymphoblastic lymphoma, CLL/small lymphocytic lymphoma (SLL) and T-lymphoblastic lymphoma. The LML of T and B cell subtypes were 45 and 74, respectively. There was a significant difference in overall survival between T-LML and B-LML (P < 0.01). Eighty one patients presented LML at the same time of the NHL diagnosis and 46 during the course (1 - 88 months) of disease. Primary nodal and extranodal NHLs developed LML were 96 and 31 cases, respectively. The clinical manifestations of LBL and SLL patients differed from that of ALL and CLL patients.

CONCLUSIONLML is not a rare manifestation of NHL. Pathological types of NHL developed LML are 15 kinds in our patients. The clinical features of LML patients are somewhat special, especially for primary extranodal LML patients.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Leukemia, Lymphoid ; classification ; pathology ; Lymphoma, Non-Hodgkin ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the expression differences of minichromosome maintenance 2 (MCM2) mRNA and protein among colon adenocarcinoma, colon adenoma and normal mucosa, and among different clinicopathological types of adenomas.

METHODSFifty specimens, including 33 colonic adenomas, 12 colonic adenocarcinomas and 5 normal colonic mucosa were selected. Each specimen was divided into two parts, one for immunohistochemistry and the other for real-time RT-PCR. Expression differences of MCM2 mRNA among the colonic adenocarcinoma, adenoma and normal colonic mucosa were evaluated by REST-XL software.

RESULTSThe expression of MCM2 was observed in the basal third to half of the colonic crypts in normal mucosa, while throughout the epithelium in the colonic adenocarcinomas and adenomas. However, the expression of MCM2 mRNA in the adenocarcinomas was significantly higher than that in the adenomas(P=0.001). The MCM2 mRNA expression was elevated in the adenoma with villous type, in the conditions of high-grade dysplasia, larger size, sessile morphology and in patients of older ages, but the difference was not significant by REST-XL (P>0.05).

CONCLUSIONThe difference of MCM2 expression between the adenoma and the adenocarcinoma indicates its potential value in the early diagnosis of colonic cancer.

Adenocarcinoma ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins ; genetics ; metabolism ; RNA, Messenger ; Young Adult

OBJECTIVETo determine the molecular basis of late onset ornithine transcarbamylase (OTC) deficiency in a Chinese family of Han nationality and the exon sequences of OTC gene of this patient.

METHODSPolymerase chain reaction-single strand conformation polymorphism and direct sequencing were used to identify the mutation type.

RESULTSA missense mutation E122G in the conserved residue of exon 4 was identified which is unreported before.

CONCLUSIONThe E122G mutation in human OTC gene may cause late onset OTC deficiency.

Age of Onset ; Base Sequence ; Child, Preschool ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Family Health ; Fatal Outcome ; Female ; Humans ; Male ; Models, Molecular ; Mutation, Missense ; Ornithine Carbamoyltransferase ; chemistry ; genetics ; Ornithine Carbamoyltransferase Deficiency Disease ; enzymology ; genetics ; pathology ; Pedigree ; Polymorphism, Single-Stranded Conformational ; Protein Structure, Secondary

OBJECTIVETo investigate the incidence, risk factors and preventative methods associated with chyle leak following complete mesocolic excision(CME) for colon cancer.

METHODSClinical data of 592 patients with colon cancer undergoing CME in the department of Colorectal Surgery in the Fujian Medical University Union Hospital from September 2000 to September 2011 were analyzed retrospectively.

RESULTSChyle leak occurred in 46 patients(7.7%). The incidence of postoperative chyle leak following right CME hemicolectomy was 13.3%(30/226), significantly higher than that after left CME hemicolectomy (4.4%). On univariate analysis, chyle leak following CME was associated with tumor size(P<0.05), tumor location(P<0.01), and lymph nodes harvested(P<0.01). Multivariate logistic regression revealed that tumor location and lymph nodes harvested were independent risk factors associated with chyle leak following CME(P<0.05).

CONCLUSIONSTumor location and lymph nodes harvested are independent risk factors for chyle leak following complete mesocolic excision for colon cancer. When the drainage output suddenly increases after oral intake resumption, the chyle test of ascitic fluid should be performed for early diagnosis and prompt management.

Aged ; Chylous Ascites ; etiology ; Colonic Neoplasms ; surgery ; Female ; Humans ; Male ; Mesocolon ; surgery ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Risk Factors

Objective: To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits.Methods: Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. Results: The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone ⅡA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05).Conclusion: The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.