Animals ; Benchmarking ; methods ; statistics & numerical data ; Dose-Response Relationship, Drug ; Humans ; Models, Statistical ; No-Observed-Adverse-Effect Level ; Risk Assessment ; methods ; statistics & numerical data ; Toxicology ; methods

OBJECTIVE To investigate the pathogenic causes of lower respiratory tract infections(LRTIs) in the elderly in Guangzhou area.METHODS Pathogens obtained from 107 patients with LRTIs were performed by multiple diagnostic tools that including bacterial culture,PCR and specific immunological assays.RESULTS A bacterial cause was established in 42(68.5%) and an atypical pathogen cause in 25(31.6%) of the 107 patients.Mycoplasma pneumoniae and Haemophilus influenzae remained the most important pathogens for LRTIs.CONCLUSIONS In the prescription of antibiotics in the elderly with LRTIs,not only bacteria but also atypical pathogens should be taken into account.

Objective To develop a method of real-time quantitative polymerase chain reaction (RQ-PCR) for detection of translocation ETS leukemia-acute myeloid leukemia 1(TEL-AML1) fusion gene in children with acute lymphoblast leukemia(ALL),and explore its clinical application in minimal residual disease (MRD) monitoring.Methods By reverse transcription and RQ-PCR,a quantifying of TEL-AML1 fusion gene was developed,and the expression levels of TEL-AML1 were detected in bone marrow (BM) samples obtained from 24 children with ALL at diagnosis and at the end of induction of remission,as well as at a series of follow-up. Moreover,the results of MRD detection by RQ-PCR were compared with that of detection by routine morphological examine of BM and cells differentiation mark analysis by flow cytometer(FCM),to evaluate the sensitivity of RQ-PCR in MRD monitoring. Results A method of RQ-PCR targeted at TEL-AML1 fusion gene was established. In 11 BM samples,which collected from TEL-AML1 positive children at the end of induction therapy and all of them achieved completely remission (CR) by routine morphological examine,5 samples were found to be MRD positive by RQ-PCR,positive ratio was 45%. There were 15 BM samples collected in maintenance therapy period,and all these samples were CR by routine morphological examine. However,by RQ-PCR,3 out of 15 samples were found to be MRD positive during maintenance therapy period. After intense and maintenance therapy,the MRD levels of the 3 children were declined to negative. In a recrudescent child,the expression of TEL-AML1 fusion gene was rose by a magnitude of 103 copies before relapse,and after induction therapy once again the patient was completely relaxed.Conclusions RQ-PCR targeted at TEL-AML1 has a higher sensitivity than conventional morphologic way and FCM. RQ-PCR can be used in the quantitative detection of MRD,and provide gist for early prognosticating a relapse and instructing clinical therapy.

?Age-related macular degeneration ( AMD) is one of the main leading causes of irreversible damage eyesight over the 50 years old people. Genetic factors play an important role in the occurrence and development of AMD. ln recent years, the studies found that complement factor H ( CFH) gene has obvious correlation with the incidence of AMD. ln this article, we reviewed the researches on the CFH in AMD.

Objective To investigate the effects ofthrce generations oftretinoids on the apoptosis of and caspase expressions in human cutaneous squamous cell carcinoma cell line SCL-1. Methods SCL-1 cells were cultured in vitro in the presence of three tretinoins, namely all-trans retinoic acid (ATRA), acitrefln and tazarotene at a concentration of 1×10-5 mol/L. On day 1, 3, 5, MTT assay and ELISA were used to detect the cell proliferation and apoptosis of these SCL-1 cells respectively; on day3, flow cytometry with Annexin V/PI was applied to analyze the cell cycle and early apoptosis, Western blot to measure the protein expressions of caspase-8 and caspase-9 in these cells. Results The growth of SCL-1 cells could be inhibited by ATRA, acitretin or tazarotene of 1×10-5 mol/L in a time-dependent manner (all P<0.01). All the three tretinoids could induce the cell apoptosis of SCL-1 cells (P<0.01), arrest them in G1-phase, and activate caspase-8 and caspase-9 (F=35.50, 25.79, respectively, both P<0.01). Of the three tretinoins, acitretin exerted the strongest effect on all the parameters tested. Conclusions Tretinoins can inhibit the growth and induce the apoptosis of cutaneous squamous carcinoma cells, which may be mediated through Fas- and mitochondria-way.

Objective To investigate the molecular transduction mechanisms of apoptosis in cuta-neous squamous cell carcinoma cell line SCL-1 induced by acitretin. Methods SCL-1 cells were cultured and continuously treated with various concentrations of acitretin. Apoptosis was assessed by enzyme-linked immunosorbent assay (ELISA) in these cells on day 1, 3 and 5. Apoptotic cells were observed by acridine orange staining on day 5. The protein expressions of Fas, FasL, Fas-associated death domain (FADD), cas-pase-8, caspase-3 and poly ADP-ribose polymerase (PARP) were examined using Western blot in SCL-1 cells treated with acitretin at 1 x 105 mol/L at different time points. Neutralizing anti-Fas antibody (ZB4,1 μg/mL) was utilized to pretreat SCL-1 cells before the treatment with acitretin, following that, ELISA was done to compare the apoptosis in cells treated with ZB4, acitretin, or the combination of ZB4 and acitretin,respectively. Results Acitretin induced the apoptosis of SCL-1 cells in a dose- and time-dependent manner.Morphologically, acitretin-treated SCL-1 cells showed a typical characteristic of apoptosis. Significant increase in Fas, FasL, and FADD protein expression, as well as the activation of caspase-8, caspase-3 and PARP were induced by the treatment with acitretin. The apoptosis absorbance value was 0.78 ± 0.04 in cells treated with acitretin alone, decreased to 0.41 ± 0.03 in cells treated with ZB4 and acitretin (P ＜ 0.05), .suggesting that ZB4 could block the apoptosis of SCL-1 cells inducedby acitretin. Conclusion Acitretin could induce the apoptosis of cutaneous squamous cell carcinoma cells likely by Fas signaling pathway.

Objective To investigate the mechanism of klotho reversing the resistance of breast cancer to paclitaxel in MCF-7/PTX cells.Methods The Klotho expression in MCF-7 and MCF-7/PTX cells was detected by Western blot.The effects of Klotho on paclitaxel resistance in MCF-7/PTX cells was measured by MTT assay.The effects of Klotho and 3-methyladenine (3-MA) on proliferation and expression of Beclin1 in MCF-7/PTX cells were detected by MTT and Western blot assay,respectively.Results The expression of Klotho in MCF-7/PTX cells was decreased compared with MCF-7 cells.Klotho could sensitize MCF-7/PTX cells to paclitaxel.The expression of Beclin1 in MCF-7/PTX cells was higher than that in MCF-7 cells.Klotho and 3-MA could decrease the expression of Beclin1 in MCF-7/PTX cells,and the effects of Klotho on paclitaxel resistance in MCF-7/PTX cells was similar to that of 3-MA.Conclusion Paclitaxel resistance in breast cancer cells is related to expression of the Klotho which can reverse the resistance of breast cancer to paclitaxel by inhibiting autophagy.

OBJECTIVEBased on two sets of data from occupational epidemiology, Benchmark dose (BMD) was applied to estimate biological exposure limit (BEL).

METHODSCadmium exposed workers were selected from a cadmium smelting and a zinc products factory and control group was selected from doctors or nurses and staff from shops living in the same area; Urinary cadmium (UCd) was used as exposure biomarker and urinary beta(2) microglobulin (UBM), NAG (UNAG) and albumin (UALB) were as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S) was used to calculate BMD.

RESULTSCalculated abnormal prevalence was based on the upper limit of 95% of effect biomarkers in control group; There are significant dose response relationship between the prevalence of effect biomarkers (UBM, UNAG and UALB) and exposure biomarker (UCd); BEL was 5 microg/g creatinine for UBM as effect biomarker, It consists with the recommendation of WHO; BEL was 3 microg/g creatinine for UNAG as effect biomarker; BEL can be estimated by using the method of BMD; the more sensitive biomarker would used, the more occupational people would protected.

CONCLUSIONThe application of BMD in estimating biological exposure limit (BEL) is proper. UNAG is suggested as most sensitive biomarker to be used to estimate BEL for cadmium exposure.

Acetylglucosaminidase ; urine ; Albuminuria ; urine ; Biomarkers ; urine ; Cadmium ; adverse effects ; urine ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Occupational Exposure ; Reference Values ; beta 2-Microglobulin ; urine

OBJECTIVETo explore the characteristics of changes in neutrophil gelatinase-associated lipocalcin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) in Phytolaccae Radix-induced kidney injury in rats and the significance of the combined detection.

METHODWistar rats were divided into three groups: high and low dose (crude drug 40, 20 g x kg(-1) x d(-1)) Phytolaccae Radix decoction groups and the control group, and orally administrated with distilled water or equal volume of Phytolaccae Radix decoction for 35 consecutive days. Their blood and urine samples were collected on day 7, 14, 21, 28, 35,42. The anatomical analysis was conducted for each group. The contents of serum total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (CR) and urinary TP and ALB were detected-by means of biochemical analyzer. The concentrations of urinary NGAL, KIM-1 and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of renal pathology were observed by light or electron microscopy. The curve areas of various serum or urine indexes and the combined detection were compared by receiver operating characteristic curve (ROC curve).

RESULTRats were given Phytolaccae Radix decoction at the doses of 40, 20 g crude drug/kg daily for 35 consecutive days to induce kidney injury characterized by the degeneration of renal tubular epithelial cell and protein cast. The injury was partially reversible during the recovery period. Compared with the control group, the content of serum BUN, CR and urinary TP in each dose group mostly showed a downward trend. On day 21, the content of urinary ALB obviously increased till the end of administration. The contents of urinary NGAL, KIM-1 and IL-18 began increasing on day 7. Since day 14, high and low dose groups showed significant difference (P<0.01). The high dose group even showed notable changes during the recovery period. According to ROC analysis, the curve areas of NGAL, KIM-1 and IL-18 were 0.846, 0.837 and 0.863 (P <0.01), respectively, much higher than that of BUN and CR. The area of the combined detection was up to 0.947.

CONCLUSIONUrinary NGAL, IL-18 and KIM-1 could forecast and indicate the occurrence and development of renal injury to some degree, and show higher sensitivity and site specificity. The combined detection could further improve the test efficiency.

Acute-Phase Proteins ; genetics ; metabolism ; Animals ; Cell Adhesion Molecules ; genetics ; metabolism ; Drugs, Chinese Herbal ; adverse effects ; Female ; Humans ; Interleukin-18 ; genetics ; metabolism ; Kidney ; drug effects ; injuries ; metabolism ; Kidney Diseases ; etiology ; genetics ; metabolism ; Lipocalins ; genetics ; metabolism ; Male ; Proto-Oncogene Proteins ; genetics ; metabolism ; Rats ; Rats, Wistar