NF-?B, a group of important transcription factors, are introduced and discussed here on several aspects: their component and molecular structure; their activity control by I?B and IKK, the mechanism of their activation; their important roles in transcriptional regulation for large numbers of genes; and their importance in immunity, inflammation, cell survival, proliferation and apoptosis. The analysis of the relation between NF-?B and disease occurrence, the analysis of the relation between NF-?B and disease therapy, and the application prospect of the new strategy regarding the novel drug design and correlative diseases therapy on the basis of NF-?B as the target, are also included.

The rat single-pass intestinal perfusion model was applied to study the effect of CYP3A and P-glycoprotein on the absorption of buagafuran in lumen of rats. Buagafuran concentrations in intestinal perfusate and blood in vena mesenterica collected at different time points after perfusion were determined by GC-MS. Permeability coefficient of buagafuran was calculated by the equation [P(lumen) = -(Q/2pirl)Ln(C(out)/C(in)) and P(blood) = (deltaM(B)/deltat)/(2pirl)]. The effects of troleandomycin (TAO, CYP3A inhibitor), cyclosporin A (CYP3A/p-glycoprotein inhibitor) on the absorption of buagafuran in lumen were observed. After rat single-pass intestinal perfusion, the cumulative amount of buagafuran in mesenteric vein of rat was 73.4, 82.9, and 98.3 pmol x cm(-2) and were increased 3.9, 4.6, and 5.6 fold by addition of inhibitor of P-gp (LSN335984), CYP3A (TAO) or P-gp and CYP3A (CsA), respectively. Moreover, the metabolized fraction of buagafuran was decreased by 12%, 11% and 21% with inhibitors. The results suggested that the poor bioavailability of buagafuran was mostly due to the interplay of P-gp and CYP3A on the absorption, transport and metabolism of buagafuran in intestine of rats.

A simple, rapid and sensitive method was developed for the quantification of tenofovir in plasma of Beagle dogs using HPLC-MS/MS analysis. The analytes tenofovir and internal standard (IS) adefovir were separated on a Zorbax SB-C18 column (3.5 microm, 100 mm x 2.1 mm, Agilent, USA) with mobile phase of methanol/water containing 0.3% formic acid using a gradient elution mode at a flow rate of 0.2 mL x min(-1). The plasma sample preparation was a simple deproteinization by the addition of 20% trichloroacetic acid followed by centrifugation. The detection was performed in positive selected reaction monitoring (SRM) mode with an electrospray ionization (ESI) source. The reactions monitored were m/z 288.1-176.2 for tenofovir and m/z 274.1-162.2 for adefovir (IS). Linear detection responses were obtained for tenofovir ranging from 10 to 5 000 ng x mL(-1). The intra- and inter-day precisions (RSD%) was no more than 6.3% with high recovery and good stability for the quantification, indicating the present method was specific, fast, accurate and reliable. The method was successfully applied to the pharmacokinetic study of two tenofovir agents. Tenofovir dipivoxil fumarate (BP0018, test agent) and tenofovir disoproxil fumarate (reference agent) were orally administrated to 8 Beagle dogs according to the 2 x 2 crossover design. Comparing with the reference agent, the longer MRT and t1/2 were obtained in the group of BP0018, while no significant difference was observed in AUC(0-t), AUC(0-infinity), C(max) and t(max) between them, suggesting that tenofovir dipivoxil fumarate was bioequivalent to the tenofovir disoproxil fumarate in Beagle dogs.

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

Adult ; Aged ; Humans ; Middle Aged ; Pneumoconiosis ; diagnostic imaging ; Radiography, Thoracic ; Retrospective Studies

OBJECTIVETo investigate the semen quality of cancer patients and search for a better way of sperm cryopreservation for them.

METHODSWe retrospectively analyzed the quality of the semen from 43 cancer patients under cryopreservation in the Sperm Bank of Zhejiang Province, and compared the semen parameters between the cancer patients and 248 normal donors as well as between the testicular cancer cases (n=22) and non-testicular cancer cases (n=21).

RESULTSThe cancer patients exhibited significantly lower semen quality than the normal donors as in sperm concentration (60.90 x 10(6)/ml vs 74.27 x 10(6)/ml), progressive motility (41.07% vs 51.79%), and recovery rate (49.98% vs 57.33%) (all P <0.05). Furthermore, the progressive sperm motility and sperm recovery rate after freezing were significantly decreased in the testicular cancer cases (15.68% and 42.81%) than in the non-testicular cancer cases (28.36% and 57.53%) (both P <0.05).

CONCLUSIONSemen quality declines in cancer patients, and therefore early sperm cryopreservation is essential for them. Due to the poor sperm motility and recovery rate of testicular cancer patients after freezing, further investigation is required on the improvement of sperm cryopreservation methods.

Adult ; Cryopreservation ; methods ; Humans ; Male ; Neoplasms, Germ Cell and Embryonal ; Semen ; Semen Analysis ; Semen Preservation ; methods ; Sperm Count ; Sperm Motility ; Testicular Neoplasms

Adult ; Drowning ; Humans ; Hydrogen Sulfide ; poisoning ; Male ; Radiography, Thoracic ; X-Ray Film ; Young Adult

OBJECTIVE To investigate the existence of genes for beta-lactam antibiotic resistance and for aminoglycosides modification enzymes(AMEs) in Pseudomonas aeruginosa(PAE) isolates from ICU patients and analyze the homology among strains.METHODS ?-Lactamase genes including TEM,SHV,OXA-10,PER,VEB,GES,CARB,IMP,VIM,SPM,GIM,DHA,FOX,MOX and oprD2,were detected by PCR amplication in 21 PAE isolates.The genes for AMES including aac(3)-Ⅰ,aac(3)-Ⅱ,aac(6′)-Ⅰ,aac(6′)-Ⅱ,ant(3″)-Ⅰ and ant(2″)-Ⅰwere determined by PCR amplification as well.RESULTS Among 21 isolates 21(100%),2(9.5%),1(4.8%),2(9.5%)and 4(19.0%) were positive for TEM,SHV,GES,CARB and VIM genes,respectively.The deletion of oprD2 gene was found in 14 out of 21 strains.Other ?-lactamase genes were absent in all isolates.As for AME genes,aac(3)-Ⅱ,aac(6″)-Ⅰ,aac(6)-Ⅱ,ant(3″)-Ⅰ,ant(2″)-Ⅰ and aac(3)-Ⅰgenes were present in 19.0%,23.8%,9.5%,4.8%,and 19.0% of 21 isolates,However,aac(3)-Ⅰ gene was no position in any isolates.CONCLUSIONS P.aeruginosa carries various beta-lactamase and AME genes in ICU patients.Genetic cluster analysis suggested that clonal propagation result in nosocomial infection of PAE.

Background The application of femtosecond laser in the corneal refractive surgery has made great progression recent years,but the morphology characteristic of corneal stroma surface after making-flap of femtosecond laser is closely concerned.Objective This study was to analyze the influence of photodisrnption of femtosecond laser on the corneal stroma surface and to investigate the effect of different laser pulse energy on the sudace ultrastructure of corneal stroma.Methods Corneal flaps were made with Visu Max femtosecond laser in 16 fresh porcine eyes with the pulse energy 125 nJ,155 nJ and 195 nJ respectively,and Moria-M2 microkeratome was used as control.Scanning electron microscopy (S-3400N Hitachi High-Technologies Corp) was used to observe and compare the ultrastructural characteristic of corneal stroma bed surface after making of corneal flap.Results The corneal strnma was evaporated and created a smooth surface when photodisrnption happened in the femtosecond laser group.Residual tissue bridges could been exhibited among the cavitation bubbles under the scanning electron microscope.Corneal strnma surface was smooth in the 125 nJ pulse energy group,but some tissue bridges still were visible.In the 155 nJ pulse energy group,much more smooth surface was seen without tissue bridges and mechanical damages on the corneal surface.However,the surface quality was worse and many tissue bridges and grooves existed in the 195 nJ pulse energy group.In addition,different sizes of slots caused by big cavitation bubbles were visible with the round and oval shape.The edges were regular and sharp with small damage zone after cutting with femtoseeond laser.However,many elevated fibril tissues could be seen on the corneal surface after making of flap with microkeratome.Many crimp and irregularity tissues were found on the surface.Blunt surface and indentations appeared in the cutting edge.Conclusions The mierostrueture of corneal stroma surface is more smoother after making of corneal flap with fentosecond laser in comparison with microkeratome.Pulse energy of 155 nJ is preferably during the making-flap with femtosecond laser.

Objective To investigate the effects of television-watching and computer-using on sleep/wake patterns, sleep duration and sleep problems of school-aged children in Shanghai. Methods A total of 4 108 school-aged children from 10 primary schools of Shanghai were enrolled by multi-stage cluster sampling and surveyed by questionnaires. The information of television-watching and computer-using, family and personal condition was investigated by self-prepared questionnaire, and the Chinese version of Children's Sleep Habits Questionnaire was employed to survey the sleep behaviors of children. The effects of television-watching and computer-using on sleep/wake patterns, sleep duration and sleep problems were analyzed by multiple linear regression analysis and Logistic regression analysis. Results The percentage of children who watched television≥2 h per day was 4.1% during weekdays, and that came to 49.2% during weekends. In terms of frequency of computer-using, most children reported "rarely" (88.2%, 0-1 time/week), followed by "often" (11.0%, 2-4 times/ week) and "usually" (0.8%, 5-7 times/week). With the age increase, the percentages of children who watched television≥2 h per day and those who "often" used computer gradually increased. It was revealed by multiple linear regression analysis and Logistic regression analysis that television-watching and computer-using were not only positively correlated with later bedtime, later wake time and shorter sleep duration but also significantly associated with sleep problems such as bedtime resistance, sleep onset delay, sleep duration disorder, sleep anxiety and parasomnia. Conclusion Television-watching and computer-using exert influences on sleep behaviors of sleep/wake patterns, sleep duration and sleep problems. Concerns about the potential negative effects of television-watching and computer-using on sleep behaviors may help to promote healthy sleep patterns and improve sleep quality.