Objective To lay the foundation for analyzing the mechanism of liver cell injury caused by mtDNA deletion and mutation in patients with obstructive jaundice. Methods 30 patients were randomly selected as obstructive jaundice group (case group) and 10 patients as control group according to the strict condition. Author makes use of the methods of PCR amplification of the entire human mitochondrial genome in 17 mismatch-specific overlapping fragments and gene sequencing results to Preliminary estimate the localizathion of hepatocyte mtDNA damage in patients with obstructive jaundice. Result Deletions and length of partial liver cells were 8429-9591 of about 1. 1 kb, 16024-60 of about 0. 6 kb, 1889-3031 of about 1. 1 kb and 4977bps common deletion and the high mutation rate of some bases in D-loop region. Conclusion There are multiple mtDNA deletions and multiple point mutations in patients with obstructive jaundice

Transforming growth factor-beta (TGFbeta) is present, predominantly in latent forms, in normal and malignant breast tissue. The mechanisms by which latent TGFbeta is activated physiologically remain largely an enigma. The objective of this study was to assess whether the proteases, cathepsin D and prostate specific antigen (PSA) could activate latent TGFbeta1 and TGFbeta2 in conditioned media of the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines, newly purchased from ATCC. Both of the cell lines were seeded in 6-well plates 2 days prior to treatment with varying concentrations of cathepsin D and PSA. Active TGFbeta1 and TGFbeta2 in the media were then measured by ELISA after 4, 8, 24 and 72 hours of treatment. TGFbeta1 and TGFbeta2 mRNA expression of both cell lines were measured by RT-PCR to determine whether any increase in level of active TGFbeta1 and TGFbeta2 was due to increased production. There was a significant increase in only active TGFbeta2 levels in the MDA-MB-231 cell line with both treatments. Cathepsin D and PSA did not have any effect on TGFbeta1 and TGFbeta2 mRNA expression. Cathepsin D and PSA were unable to activate latent TGFbeta1 and TGFbeta2 in these two breast cancer cell lines. A constant level of TGFbeta2 mRNA in the control and treated MDA-MB-231 cells suggests that the increase in level of active TGFbeta2 was not a result of increased production but was likely to be due to activation by a mechanism independent of cathepsin D and PSA.
Transforming Growth Factor beta ; Cell Line ; Cathepsin D ; seconds ; public service announcement

Factor VIIa ; Genetic Therapy ; Hemophilia A ; drug therapy ; epidemiology ; genetics ; physiopathology ; History, 21st Century ; Humans ; Recombinant Proteins ; Singapore ; epidemiology

The article introduced the goal,principle,method and the characteristics of the physical diagnosis operation skill of our academy training,especially emphasizing on the training way,the standard and the effect.

BACKGROUNDHost immune responses against hepatitis B virus (HBV) induced by antiviral therapy play a crucial role in viral clearance. To further investigate the immune mechanisms underlying the differences between respondents and non-respondents, we analyzed myeloid dendritic cells (mDCs), plasmacytoid dendritic cells (pDCs), FoxP3(+) regulatory T cells (FoxP3(+) Treg) and programmed death 1 (PD-1) expression in CD4(+)/CD8(+) T cells in chronic hepatitis B patients undergoing pegylated interferon (PegIFN)α-2b treatment.

METHODSPatients received PegIFNα-2b for 24 or 48 weeks, with follow-up at 24 weeks. The frequencies of mDCs, pDCs, FoxP3(+) Treg, and PD-1 expression by CD4(+)/CD8(+) T cells were evaluated by flow cytometry at baseline, weeks 4 and 12, end of treatment, and follow-up (12/24 weeks).

RESULTSIn HBeAg seroconverters (respondents), the mDC relative frequency decreased at week 4 and then rebounded at week 12. The pDC relative frequency decreased consistently. In non-HBeAg seroconverters (non-respondents), both mDC and pDC frequencies decreased slightly. The FoxP3(+) Treg relative frequency decreased during treatment and remained low during follow-up in respondents, while in non-respondents it decreased slightly during therapy but rebounded after discontinuation. In patients with HBeAg < 17.55 PEI-U/ml at week 12 and < 8.52 PEI-U/ml at week 24, the FoxP3(+) Treg frequency decreased during treatment and at follow-up. In respondents, CD4(+)PD-1 and CD8(+)PD-1 levels decreased at week 4 and remained low at week 12. In non-respondents, PD-1 expression decreased at week 4 but rebounded at week 12.

CONCLUSIONSThe results indicate that the dynamic changes in DCs, FoxP3(+) Treg frequency, and PD-1 expression by CD4(+) and CD8(+) T cells exhibit different trends in HBeAg and non-HBeAg seroconversion patients. During PegIFNα-2b treatment of chronic hepatitis B patients, these changes may be of predictive value for HBeAg seroconversion. HBsAg and HBeAg levels are related to FoxP3(+) Treg frequency.

Adult ; Antiviral Agents ; therapeutic use ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; DNA, Viral ; blood ; Female ; Forkhead Transcription Factors ; analysis ; Hepatitis B ; drug therapy ; immunology ; Hepatitis B e Antigens ; blood ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Polyethylene Glycols ; therapeutic use ; Programmed Cell Death 1 Receptor ; analysis ; Recombinant Proteins ; therapeutic use ; T-Lymphocytes ; immunology ; T-Lymphocytes, Regulatory ; immunology

Seven terpenoids and three sterols were isolated from the methanol extracts of the aerial parts of Ricinus communis by chromatography methods and their structures were identified by spectra analysis as ficusic acid( 1), phytol(2), callyspinol(3) , lupeol(4), 30-norlupan-3beta-ol-20-one(5) , lup-20(29)-en-3beta,15alpha-diol(6) , acetylaleuritolic acid( 7), stigmast4-en-3-one(8) , stig-mast-4-en-6beta-ol-3-one(9) , and stigmast4-en-3,6-dione(10). Compounds 1-3 and 5-10 were obtained from this species for the first time and 5 and 6 showed significant inhibitive activity and good selectivity against 11beta-HSD of mouse and human in vitro. [Key words] Ricinus communis; terpenoids; sterols; 11beta-HSD
11-beta-Hydroxysteroid Dehydrogenase Type 1 ; antagonists & inhibitors ; 11-beta-Hydroxysteroid Dehydrogenase Type 2 ; antagonists & inhibitors ; Animals ; Diabetes Mellitus ; drug therapy ; enzymology ; Humans ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Inhibitory Concentration 50 ; Mice ; Ricinus ; chemistry ; Sterols ; pharmacology ; therapeutic use ; Terpenes ; pharmacology ; therapeutic use

Animals ; Athletic Performance ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Morinda ; Myocardium ; metabolism ; Physical Conditioning, Animal

Objective To assess the diagnostic value of contrast enhanced ultrasound (CEUS) in liver metastases. Methods Thirty-six patients were examined with conventional ultrasonography, then underwent continuous real-time CEUS with low mechanical index. The size, location, number and perfusion patterns of liver metastases were evaluated. Results In 36 patients, 67 liver metastases were found with conventional ultrasound and 106 liver metastasis were found with CEUS. The perfusion patterns of lesions were in four types: ①Thirty-seven lesions (34.91%) showed as total enhancement during the early arterial phase and hypoechoic appearance during the portal venous phase and the late phase;②Fifty-six lesions (52.83%) showed a peripheral rim-like hyperechonic enhancement during the arterial phase and fast wash-out in the portal phase;③Twelve lesions (11.32%) showed as isoechoic enhancement during the arterial phase and the portal phase and was hypoechoic in the late phase;④One lesion (0.94%) showed hypoechoic appearance during all phases. The dimension of the lesions played an important role in the perfusion patterns. Conclusion The enhancement pattern and time of lesions are closely correlated with the tumor arterial supply. CEUS has high value in diagnosing liver metastases.

OBJECTIVE Hypericin, a powerful naturally photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. In the present study, we aimed to evaluate the skin penetrability of a topically applied hypericin, expecting reducing the risk of prolonged skin photosensitivity, which often occurs after systemic administration. METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers. In vivo studies, fluorescence microscopy was performed to examine the distribution of hypericin in the skin, macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin. RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mice skin, spread to the dermis, and resulted in obvious photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin 7 d after hypericin-PDT treat?ment. CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases.