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Objective: To establish the murine xenograft model of human prostate cancer by grafting tumor tissues beneath the renal capsule of intact male athymic mouse., Methods: Fifteen SCID mice were randomly divided into 3 groups (n = 5 each). Tissue recombinants were prepared in vitro with newborn BALB/c murine seminal vesicle mesenchyme (SVM) and surgical isolated human prostate cancer tissues by using recombination technique and then grafted beneath the renal capsule of intact male athymic mouse. At Week 4 after initial implantation, grafts were harvested and tumor sizes calculated. The expressions of human specific markers CK8/18 and vimentin were evaluated by immunohistochemistry to identify the human prostatic origin in grafts. P63 protein, a basal cell marker, was detected in prostate basal membrane to identify whether it was benign or malignant tissue. And the study control was prepared by implanting prostate cancer tissues alone under the renal capsule in SCID mouse., Results: Of all 78 implantation cases in 15 mice, the tumor-forming rates were 100% (39/39) and 94.1% (37/39) respectively in the recombination and prostate cancer alone grafting groups. The recombination group was shown to be more efficient in terms of tumor size and weight in comparison with the prostate cancer alone group [(9.7 ± 3.1) vs (6.8 ± 2.0) mm(3), (12.1 ± 3.6) vs (8.2 ± 2.2) µg, P < 0.01]. There was no difference in serum PSA level between two groups. Grafts were confirmed as human prostate cancer tissues with the expressions of CK8/18 and vimentin. No expression of P63 was detected., Conclusion: The xenograft murine model of human prostate cancer is successfully established. It contains stroma components and is particularly suitable for studying the interaction of stroma and epithelia in the in vivo progression of prostate cancer.

This paper demonstrates the embellishment of existing microfluidic devices with integrated three dimensional (3D) micronanostructures via femtosecond laser micronanofabrication, which, for the first time, proves two-photon photopolymerization (TPP) to be a powerful technology for chip functionalization. As representative examples, microsieves with various pore shape and adjustable pore size were successfully fabricated inside a conventional glass-based microfluidic channel prepared by wet etching for microparticle separation. Moreover, a fish scale like microfilter was also fabricated and appointed as a one-way valve, which showed excellent performance as we expected. These results indicate that such embellishment of microfluidic devices is simple, low cost, flexible and easy to access. We believe that, combined with TPP, the application of lab-on-chip devices would be further extended.

We have studied the ultrafast dynamics of two-photon-pumped amplified spontaneous emission (ASE) from a single crystal by the time-resolved fluorescence upconversion technique. With the increase of two-photon pump intensities, the emission decay time is dramatically shortened by 30 times (from 3ns to approximately 87 ps), and the energy migration rate is acutely enhanced when ASE occurs. The stripe length is also found to play an important role in the formation of the ASE. Meanwhile, the gain coefficient is evaluated to be 15cm(-1) for 560nm at an excitation intensity of 2.3mJ/pulse/cm(2) by the variable stripe length technique.

In this paper, one simple method to control two-direction anisotropic wetting by regular micropearl arrays was demonstrated. Various micropearl arrays with large area were rapidly fabricated by a kind of improved laser interference lithography. Specially, we found that the parallel contact angle (CA) theta(2) decreased from 93 degrees to 67 degrees as the intensity ratio of four laser beams increased from 2:1 to 30:1, while the perpendicular CA theta(1) determined by the thickness of the resin remained constant. This was interpreted as the decrease of height variations Delta h from 1100 to 200 nm along the parallel direction caused by the increase of the intensity ratio. According to this rule, both theta(1) and theta(2) could be simultaneously controlled by adjusting the height variation Delta h and the resin thickness. Moreover, by combining appropriate design and low surface energy modification, a natural anisotropic rice leaf exhibiting CAs of 146 degrees +/- 2 degrees/153 degrees +/- 3 degrees could be mimicked by our anisotropic biosurface with the CAs 145 degrees +/- 1 degrees/150 degrees +/- 2 degrees. We believe that these controlled anisotropic biosurfaces will be helpful for designing smart, fluid-controllable interfaces that may be applied in novel microfluidic devices, evaporation-driven micro/nanostructures, and liquid microdroplet directional transfer.

Instruction: We determined whether adjuvant vinorelbine/paclitaxel plus carboplatin prolonged overall survival among patients with completely resected stage IIIA-N2 non-small cell lung cancer (NSCLC)., Methods: We randomly assigned patients with completely resected stage IIIA-N2 NSCLC to a control group or to a treatment group with vinorelbine/carboplatin or paclitaxel/carboplatin doublet adjuvant chemotherapy. The primary endpoint was overall survival; secondary endpoints were disease-free survival and the toxicity and safety of the regimen., Results: This trial was terminated before accumulation of the planned numbers for registration because of the results of bigger clinical trial. Finally, 150 patients underwent randomization to vinorelbine/paclitaxel plus carboplatin (79 patients) or observation. In the chemotherapy group, 38 patients received vinorelbine plus carboplatin and 41 patients received paclitaxel plus carboplatin. In both groups, the median age was 57 years, 73% were men, and 28% had squamous carcinoma. Chemotherapy caused neutropenia in 82% of the patients (including grade 3 and 4 neutropenia in 42%), and there were no treatment-related deaths in this trial. After a median follow-up of 29 months (range, 1-110 months), the overall survival was significantly prolonged in the chemotherapy group, when compared with the observation group (33 months [95% confidence interval {CI}, 27.4-38.6] versus 24 months [95% CI, 15.8-32.2], p = 0.037), as was disease-free survival (32 months [95% CI, 21.3-42.7] versus 20 months (95% CI, 13.1-26.9), p = 0.020). The 5-year overall survival rates were 31.1% and 19.1%, respectively., Conclusions: Although with limitations, this clinical trial showed that adjuvant vinorelbine/paclitaxel plus carboplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected stage IIIA-N2 NSCLC.

A novel cationic Ir(III) complex [Ir(Bpq)(2)(CzbpyCz)]PF(6) (Bpq=2-[4-(dimesitylboryl)phenyl]quinoline, CzbpyCz = 5,5'-bis(9-hexyl-9H-carbazol-3-yl)-2,2'-bipyridine) containing both triarylboron and carbazole moieties was synthesized. The excited-state properties of [Ir(Bpq)(2)(CzbpyCz)]PF(6) were investigated through UV/Vis absorption and photoluminescence spectroscopy and molecular-orbital calculations. This complex displayed highly efficient orange-red phosphorescent emission with an emission peak of 583 nm and quantum efficiency of Phi=0.30 in dichloromethane at room temperature. The binding of fluoride ions to [Ir(Bpq)(2)(CzbpyCz)]PF(6) can quench the phosphorescent emission from the Ir(III) complex and enhance the fluorescent emission from the N--N ligand, which corresponds to a visual change in the emission from orange-red to blue. Thus, both colorimetric and ratiometric fluoride sensing can be realized. Interestingly, an unusual intense absorption band in the visible region was observed. And the detection of F(-) ions can also be carried out with visible light as the excitation wavelength. More importantly, the linear response of the probe absorbance change at lambda=351 nm versus the concentration of F(-) ions allows efficient and accurate quantification of F(-) ions in the range 0-50 microM.

E, E-1, 4-bis[4'-(N,N-dibutylamino)styryl]-2,5-dimethoxy-benzene (DBASDMB) organic crystals with high crystalline quality, large size and excellent optical properties are prepared. The linear and nonlinear properties in the crystal are comparatively studied. The relaxation dynamics pumped by two-photon are very similar with that pumped by one-photon. The crystal exhibits very strong two-photon excited fluorescence and amplified spontaneous emission. Efficient two-photon absorption, reasonably high fluorescent quantum efficiency, and high crystal quality together with stimulated emission make organic crystals ideal for the application in frequency upconversion and other optoelectronic fields.

Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6h that was sustained throughout the 21day immobilization period. MMP-3 upregulation was higher in the medial condyle than the lateral, and was greatest in the superficial cartilage zone, followed by middle and deep zones. These areas also showed decreases in safranin O staining, consistent with reduced cartilage proteoglycan content, as early as 7days after immobilization. One hour of daily moderate mechanical loading, applied as passive joint motion, reduced the MMP-3 and ADAMTS-5 increases that resulted from immobilization, and also prevented changes in safranin O staining. Intra-articular injections of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), dampened the catabolic effects of a 7day immobilization period, indicating a likely requirement for MMP-3 in the regulation of proteoglycan levels through ADAMTS-5. These results suggest that biomechanical forces have the potential to combat cartilage destruction and can be critical in developing effective therapeutic strategies., (Copyright (c) 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.)

Background: Adjuvant cisplatin-based chemotherapy benefits selected patients with stages II and III non-small cell lung cancer (NSCLC). However, carboplatin being tolerated better than cisplatin, carboplatin-based adjuvant therapy may have better chemotherapy compliance. This study aimed to investigate the feasibility and toxicity of adjuvant carboplatin and docetaxel in patients with completely resected locally advanced NSCLC., Methods: Eighty patients with completely resected locally advanced NSCLC were enrolled in this trial. Adjuvant chemotherapy was initiated between 1 and 4 weeks after surgery, and consisted of four cycles of carboplatin (AUC=5), and docetaxel (Taxotere, 75mg/m(2)) every 3 weeks, after which patients received prophylactic G-CSF supportive therapy., Results: Patient demographics were: Median age 55 years (range 34-73): gender ratio was 56.3% male/43.7% female: 72.5% of the patients were at stage IIIA and 27.5% were at stage IIIB. The two most common histologies were adenocarcinoma (62.5%) and squamous cell carcinoma (17.5%). Sixty-six patients (82.5%) received four cycles of therapy over a 12-week period. Fourteen patients (17.5%) did not complete therapy due to: patient refusal (n=12), severe adverse events (n=1) and bone metastases during chemotherapy (n=1). No treatment related deaths were observed and the primary adverse events were hematologic toxicity, alopecia, fatigue and gastointestinal reaction (nausea, vomiting and diarrhea)., Conclusion: Combination therapy with carboplatin and docetaxel with the use of G-CSF supportive therapy has an acceptable toxicity profile such that the majority of patients completed four cycles of therapy in 12 weeks., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Reported is femtosecond laser direct patterning of sensing materials toward flexible integration of micronanosensors (FIMS), meaning the capability to fabricate multiple functional sensors of smaller size on a nonflat surface of a substrate that is not limited to silicon. As a representative example, a photosensitive SnO(2) colloidal solution (sol) was developed, from which complex micronanostructures were written via a two-photon absorption process. After thermal decomposition of organic components, the patterned SnO(2) microsensors responded to relative humidity (RH) with a variation range of 5 orders of magnitude. FIMS would open a new door for miniaturization of micronanosensors expected in intelligent microsystems.

Arsenic, an ancient drug used in traditional Chinese medicine, has attracted worldwide interest because it shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). PML and PML-RARalpha degradation is triggered by their SUMOylation, but the mechanism by which As2O3 induces this posttranslational modification is unclear. Here we show that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RARalpha and PML. Arsenic binding induces PML oligomerization, which increases its interaction with the small ubiquitin-like protein modifier (SUMO)-conjugating enzyme UBC9, resulting in enhanced SUMOylation and degradation. The identification of PML as a direct target of As2O3 provides new insights into the drug's mechanism of action and its specificity for APL.

The influence of biomechanical stimuli on modulating cartilage homeostasis is well recognized. However, many aspects of cellular mechanotransduction in cartilage remain unknown. We developed a computer-controlled joint motion and loading system (JMLS) to study the biological response of cartilage under well-characterized mechanical loading environments. The JMLS was capable of controlling (i) angular displacement, (ii) motion frequency, (iii) magnitude of the axial compressive load applied to the moving joint, and it featured real-time monitoring. The accuracy and repeatability of angular position measurements, the kinematic misalignment error as well as the repositioning error of the JMLS were evaluated. The effectiveness of the JMLS in implementing well-defined loading protocols such as moderate Passive Motion Loading (PML) and increased Compressive Motion Loading (CML) were tested. The JMLS demonstrated remarkable accuracy and reliability for the measurement and kinematics tests. Moreover, the effectiveness test demonstrated the ability of the JMLS to produce an effective stimulus via PML that led to the suppression of the catabolic effects of immobilization. Interestingly, the biological response of the CML group was catabolic and exhibited a pattern similar to that observed in the immobilization group. This novel non-invasive system may be useful for joint biomechanics studies that require different treatment conditions of load and motion in vivo.

Joint tissues are exquisitely sensitive to their mechanical environment. Indeed, mechanical loading may be the most important external factor regulating the development and long-term maintenance of joint tissues. Moderate mechanical loading maintains the integrity of articular cartilage, and under these conditions of homeostasis, matrix metalloproteinases (MMPs) are expressed at modest levels. However, both disuse and overuse can result in altered likely high levels of MMP expression, leading to cartilage degradation. The transcriptional regulator ED-rich tail 2 (CITED2) is expressed in chondrocytes in a load-dependent manner but in a pattern inversely related to that of MMPs. CITED2 mediates the moderate load-induced suppression of MMPs, possibly by competing with Ets-1, a known MMP transactivator, for binding to the co-activator p300, suggesting a mechanism for transcriptional suppression by CITED2. These findings suggest that CITED2 may act as a mechanosensitive molecular switch regulating cartilage matrix breakdown. This regulatory pathway could be exploited clinically to limit pathologic cartilage degradation.

Electro-optic probing of electric fields has been considered as a promising approach for integrated circuit diagnosis. However, the method is subject to relatively weak voltage sensitivity. In this Letter, we solve the problems with electro-acoustic effect. In contrast to the general electro-optic effect, the light phase modulation induced by the acoustic effect is 2 orders of magnitude stronger at its resonant frequency, as we observed in a GaAs thin film probe. Furthermore, this what we believe to be a novel method shows a highly reproducible linearity between the detected signals and the input voltages, which facilitates the voltage calibration.

Objective: To investigate the molecular pathway of substance P (SP) to induce osteoblastic differentiation., Methods: Mesenchymal stem cells were isolated and cultured. The cultures were divided into four groups with Group A (control group) cultured without any factors, Group B cultured with SP, Group C cultured with SP and SP receptor neurokinin-1 (NK1) antagonist, and Group D cultured with SP NK1 antagonist respectively to induce osteoblastic cells differentiation. Osterix gene expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) for three times after 1-2 weeks of cultivation and the results were analyzed by one-way analysis of variance (ANOVA)., Results: The log phase of bone marrow stromal cells appeared at 4-6 days. ALP staining revealed that the majority of cells, more than 95%, were positive and small blue-purple granules were found in the cytoplasm. And Group B, treated with SP, showed a higher level of ALP activity than the other three groups. Meanwhile, RT-PCR found that Osterix expression in Group B was obviously up-regulated, compared with other groups. But Osterix expression in Group D had no remarkable differences, compared with the controls., Conclusions: SP can up-regulate Osterix gene expression to stimulate differentiation of mesenchymal stem cells into osteoblastic cells at the final stage. The regulatory effect of SP on Osterix expression was dependant on SP NK1 receptors.

Effective upconversion emission from an organic crystal of cyano-substituted oligo (p-phenylenevinylene) (CNDPASDB) based on two-photon absorption is presented. Frequency upconverted cavityless lasing, or amplified spontaneous emission, from the crystal pumped by a femtosecond laser of 800 nm was observed when the excitation energy exceeded the threshold of 1.3 mJpulse(-1)cm(-2). Its polarization contrast was estimated to be approximately 0.93. This large ratio is due to the unified unidirectional configuration of the molecular long axis in crystal, beneficial to the stimulated emission with a low threshold. These results indicate that the present CNDPASDB crystal has a potential for upconversion laser device application.

This study describes the development and application of a novel rat patellar tendon model of mechanical fatigue for investigating the early in vivo response to tendon subfailure injury. Patellar tendons of adult female Sprague-Dawley rats were fatigue loaded between 1-35N using a custom-designed loading apparatus. Patellar tendons were subjected to Low-, Moderate- or High-level fatigue damage, defined by grip-to-grip strain measurement. Molecular response was compared with that of a laceration-repair injury. Histological analyses showed that progression of tendon fatigue involves formation of localized kinked fiber deformations at Low damage, which increased in density with presence of fiber delaminations at Moderate damage, and fiber angulation and discontinuities at High damage levels. RT-PCR analysis performed at 1- and 3-day post-fatigue showed variable changes in type I, III and V collagen mRNA expression at Low and Moderate damage levels, consistent with clinical findings of tendon pathology and were modest compared with those observed at High damage levels, in which expression of all collagens evaluated were increased markedly. In contrast, only type I collagen expression was elevated at the same time points post-laceration. Findings suggest that cumulative fatigue in tendon invokes a different molecular response than laceration. Further, structural repair may not be initiated until reaching end-stage fatigue life, where the repair response may unable to restore the damaged tendon to its pre-fatigue architecture., (Copyright 2009. Published by Elsevier Ltd.)

Cyano-substituted oligo (alpha-phenylenevinylene)-1,4-bis(R-cyano-4-diphenylaminostyryl)-2,5-diphenylbenzene (CNDPASDB) molecules are studied in solution and aggregate state by time-resolved fluorescence techniques. CNDPASDB exhibits a strong solvent polarity dependent characteristic of aggregation-induced emission (AIE). By time-dependent spectra, the gradual transition from local excited state to intramolecular charge transfer state with the increasing solvent polarity is clearly resolved. The transition time in high polarity solvent DMF is very fast, around 0.5 ps, resulting in a low fluorescence quantum yield. While in aggregate state, the intramolecular torsion is restricted and the local environment becomes less polar. Thus, the intramolecular charge transfer state is eliminated and efficient AIE occurs.

Objective: To evaluate xerostomia, mucositis and dental caries during head and neck radiotherapy., Methods: Twenty patients with nasopharyngeal carcinoma were included. Oral examinations were conducted before radiotherapy, after dosage of 2000 cGy irradiation, immediately after the termination of radiotherapy, and 1 month and 6 months after termination of the radiotherapy. Oral hygiene instruction, effective oral care and dental intervention were performed during the treatment. Salivary flow rate was evaluated by modified Schirmer's test. Xerostomia, mucositis and dental caries status were evaluated based on oral examinations., Results: Salivary flow rate decreased significantly after the first dosage of 2000 cGy, and was aggravated with the increase in irradiation dosage until the termination of radiotherapy. Xerostomia and mucositis were observed in parallel with the reduction of saliva flow rate, and were aggravated with the increase in irradiation dosage. Mucositis began to recover within 1 month after the termination of radiotherapy and fully recovered within 6 months after the termination of the radiotherapy. Six months after the termination of irradiation, new carious lesions were detected in two patients., Conclusion: Oral sequelae developed during radiotherapy of the head and neck. Oral health instructions and effective intervention were essential before, during and after the radiotherapy.

The PAHs-degradation bacterium strain JY11 was newly isolated from the polluted soil in Jinan Oil Refinery Factory, Shandong Province of China. The isolate was identified as Janibacter anophelis with respect to its 16S rDNA sequence, DNA-DNA relatedness and fatty acid profiles, as well as various physiological characteristics. The strain was Gram-positive, non-motile, non-spore-forming, short rods in young culture, 0.8-1.0 microm in diameter and 1.3-1.6 microm long, and coccoid cells in the stationary phase of growth that are 1.0-1.2 microm in diameter and 1.3-1.5 microm long, occurred in pairs and sometimes in chains or in group, aerobic, oxidase-week positive, catalase-positive. J. anophelis strain JY11 can utilize naphthalene, phenanthrene, anthracene, pyrene, xylene, methanol, ethanol and salicylic acid as sole carbon source. The strain could remove 98.5% of phenanthrene, 82.1% of anthracene, and 97.7% of pyrene with an initial concentration of 500 ppm in five days without adding co-metabolism substrates and surfactants.

Background: Renal transplantation is currently the prevalent therapy for most patients with end-stage renal disease. No clinical markers for such rejection have been universally accepted. We aimed to investigate the possibility of use of human leukocyte antigen (HLA) class I (ABC) on peripheral blood CD3+/CD8+ T lymphocytes as a marker of acute rejection., Methods: For recipients undergoing renal transplantation from September 2007 to November 2008, peripheral blood samples were obtained pretransplantation and at days 3 and 7 posttransplantation when the patients were still hospitalized and at weeks 2 and 3 and months 1, 2, 3, and 6 posttransplantation. For patients with fever, lumbodynia, gross hematuria, or oliguria after transplantation, blood samples were collected immediately before and at days 3 and 7 after the administration of anti-inflammatory regents. The level of HLA class I (ABC) on peripheral-blood CD3+/CD8+ T lymphocytes was measured on flow cytometry., Results: For the 79 transplant recipients, the level of HLA class I (ABC) on peripheral-blood CD3+/CD8+ T lymphocytes was consistently elevated during the first 3 weeks after transplantation, declined gradually to pretransplantation levels, then tapered off and remained stable. Patients experiencing acute rejection (AR) or not after transplantation did not differ in level of HLA class I (ABC) up to 6-month follow-up, except at days 14 and 21 after transplantation, when the level was higher for patients experiencing AR (P<0.01)., Conclusions: Upregulation of HLA class I (ABC) on peripheral-blood CD3+/CD8+ T lymphocytes could be used as an accurate and reliable predictor of AR after renal transplantation.

Background and Objective: Even though most breast cancers occur in postmenopausal women in western countries, age <35 is one of the prognostic factors. This study was to compare the clinicopathologic characteristics and prognosis between premenopausal breast cancer patients aged of <35 and > or =35 in south China, and to explore the prognostic factors., Methods: A total of 905 consecutive premenopausal patients were evaluated, with first diagnosis of breast cancer referred to surgery at the Sun Yat-sen University Cancer Center from October 2003 to December 2006. The clinicopathologic factors and the survival rates between the very young group(aged of <35 at diagnosis) and the non-young group(aged of > or =35 at diagnosis) were retrospectively compared., Results: The overall median follow-up time was 27.77 months. The 3-year disease-free survival rate was significantly lower (78.0% vs. 89.1%, P<0.001) and the 3-year survival rate relatively lower(94.3% vs. 96.8%, P=0.10) in the very young group than in the non-young group. In addition, the 3-year survival and disease-free survival rates were significantly lower in the very young group with HR (hormone receptor)-positive than in the non-young group (P<0.05). The univariate and multivariate analysis of clinicopathologic characteristics between two groups showed that age <35 at diagnosis, axillary lymph node involvement, presence of vascular invasion, and high expression of Ki67 were risk factors for recurrence., Conclusion: Compared with non-young premenopausal patients, very young breast patients with HR-positive cancer have a worse outcome.

The enhanced second-harmonic (SH) generation from Si (111) stripes induced by external cylindrical strain is investigated. The dependence of the intensity of the strain-induced SH on the sample azimuth shows that the Si under cylindrical strain has 3m symmetry, which is similar to that of the Si (111) surface. Further studies indicate that the intensity of the enhanced SH is a quadratic function of the cylindrical strain within the magnitude that the Si stripe can bear. For the p-polarized and s-polarized SH, the intensities are, respectively, enhanced by 47.9% and 13% at epsilon(0)=2.93x10(-4). The enhancement of SH is due to the contributions from the strain-induced second-order nonlinear susceptibility chi(strain)(2) to the bulk dipole.

The transcription regulator CITED2 (CBP/p300-Interacting-Transactivator-with-ED-rich-tail-2) is known to suppress genes mediating angiogenesis and extracellular matrix (ECM) remodeling. However, it is unclear whether CITED2 has a role in controlling skeletal repair or remodeling. We tested the hypothesis that CITED2 functions in bone fracture healing by suppressing the expression of genes critical to ECM remodeling, angiogenesis and osteogenesis, importantly the matrix metalloproteinases (MMPs). Three hours following mandibular osteotomy or sham surgery of adult rats, osteotomy fronts were harvested and the expression of CITED2 and genes associated with fracture healing was ascertained by quantitative PCR. In parallel, gain-of-function studies examined the effect of overexpressing CITED2 on the expression and activity of several MMPs. In the fractured mandible, CITED2 expression was inversely related to the expression of MMP-2, -3, -9, -13, VEGF, HIF-1alpha, M-CSF, RANK-L, and OPG. Consistent with this, the over-expression of CITED2 in osteoblasts inhibited the expression and activity of MMP-2, -3, -9, and -13. Taken together, the studies suggest that CITED2 is a critical upstream regulator of fracture healing. The suppression of CITED2 early after fracture may allow an optimal initiation of the healing response.

Microfluidic researches are now resorting to advanced micro-nanoprocessing technologies for production of more functional "lab-on-a-chip" systems. However, two-photon polymerization (TPP), a powerful designable micro-nanofabrication approach, has not been put to use on the exciting field, largely due to the difficulties in forming buried channels. Here, we solve the problem by TPP prototyping of nanoshells, for which the usage of the negative tone resin SU-8 is found critical. The fabrication efficiency improved by orders of magnitude, together with the prospect of integration of movable micro-mechanical and optical components into the chip would make TPP a promising enabling tool for the micro-analytical systems. Finally, a 25 microm length functional microvalve in a microfluidic channel was rapidly realized and its "ON" and "OFF" states were tested.

Aim: To explore the effect of silencing of signal transducer and activator of transcription 3 (STAT3) expression by RNA interference (RNAi) on growth of human hepatocellular carcinoma (HCC) in tumor-bearing nude mice in vivo., Methods: To construct the recombinant plasmid of pSilencer 3.0-H1-STAT3-siRNA-GFP (pSH1-siRNA-STAT3) and establish the tumor-bearing nude mouse model of the HCC cell line SMMC7721, we used intratumoral injection together with electroblotting to transfect the recombinant plasmid pSH1-siRNA-STAT3 into the transplanted tumor. The weight of the nude mice and tumor volumes were recorded. STAT3 gene transcription was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Level of protein expression and location of STAT3 were determined by Western blotting and immunohistochemical staining. STAT3-related genes such as survivin, c-myc, VEGF, p53 and caspase3 mRNA and protein expression were detected in tumor tissues at the same time. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptosis of tumor cells., Results: The weight of the treated nude mice increased, and the tumor volume decreased markedly compared with those of the mock-treated and negative control groups (P < 0.01). The results of RT-PCR and Western blotting showed that mRNA and protein levels of STAT3 declined markedly in the treated group. The change in STAT3-related gene expression in tumor tissues at the mRNA and protein level also varied, the expression of survivin, VEGF and c-myc were obviously reduced, and expression of p53 and caspase3 increased (P < 0.01). Most of the tumor tissue cells in the treated group developed apoptosis that was detected by TUNEL assay., Conclusion: Silencing of STAT3 expression by RNAi significantly inhibits expression of STAT3 mRNA and protein, and suppresses growth of human HCC in tumor-bearing nude mice. The mechanism may be related to down-regulation of survivin, VEGF and c-myc and up-regulation of p53 and caspase3 expression. Accordingly, the STAT3 gene may act as an important and effective target in gene therapy of HCC.

Synaptotagmin I is a key synaptic protein involved in both exocytosis and endocytosis. We aimed to investigate Synaptotagmin I expression in the anterior temporal neocortex of epilepsy patients, and to explore the possible role of Synaptotagmin I in refractory epilepsy. In the present study, 30 epilepsy patients were divided into refractory epilepsy and non-refractory epilepsy groups, another 15 histologically normal anterior temporal lobes from head trauma patients were used as control group. The results were compared among different groups. The findings were consistently observed using immunohistochemistry, immunofluorescence, and Western blotting technique. Synaptotagmin I was mainly expressed in the cytoplasm and cytomembrane of neurons. The expression of Synaptotagmin I in refractory epilepsy group was significantly higher than that in the control and non-refractory epilepsy groups. These findings provide new information in the epileptogenesis of refractory epilepsy, and suggest that Synaptotagmin I might be involved in human refractory epilepsy. Further studies will be required to elucidate the mechanism by which Synaptotagmin I plays role in refractory epilepsy.

We propose a quantum trajectory analysis of a scheme to measure the states of a coupled-dot device (qubit) where there is a fluctuating energy gap Δ between the two states. The system consists of the qubit and a readout dot coupled to source and drain leads. The tunnel rate through the detector is conditioned by the occupation number of the nearer quantum dot (target) of the qubit and therefore probes the states of the qubit. We derive a Lindblad-form master equation to calculate the unconditional evolution of the qubit and a conditional stochastic master equation calculating the conditional evolution for different tunneling rates. The results show the effects of various device parameters and provide the optimum selection and combination of the system structure.

Objective: To analyze the chromosomal karyotype aberrations of exfoliated urothelial cells in superficial bladder cancer patients and the correlation thereof to recurrence of carcinoma., Methods: Voided urine samples were collected from 42 patients with pathologically confirmed recurrent bladder cancer and 24 bladder cancer patients without pathologically confirmed recurrence, all of which had undergone complete transurethral resection and had been followed up for more than 3 years. Fluorescence in situ hybridization (FISH) was used with Spectrum Green to label the chromosome 7 and Spectrum Red to label the chromosome 17 of the exfoliated urothelial cells., Results: The aneuploidy rates of chromosomes 7 and 17 were 48.5% (32/66) and 50.0% (33/66) respectively, and the co-aneuploidy rate of chromosomes 7 and 17 was 25.8% (17/66). In the patients with G(2/3) superficial bladder cancer, the aneuploidy rate of chromosomes 17 of those with recurrence was 64.3%, significantly higher than that of patients without recurrence (22.2%, P < 0.05). However, there were not significant differences in the aneuploidy rates of chromosomes 7 and 17 in the pT(a) and pT(1) superficial bladder cancer patients with or without recurrence (all P > 0.05), however, the co-aneuploidy rate of chromosomes 7 and 17 of the patients with recurrence was 47.8%, significantly higher than that of the patients without recurrence (12.5%, P < 0.05). Fourteen of the 42 patients with recurrence showed progression, i.e., with increased grade or stage (>/= pT(2)). The aneuploidy rates of chromosomes 7 and 17 of these 14 patients were 78.6% and 92.9% respectively, both significantly higher than those of the 28 patients without progression (42.9% and 46.4% respectively, both P < 0.05)., Conclusion: Abnormality in the chromosomes in exfoliated urothelial cells of superficial bladder cancer patients using FISH technique helps predict recurrence and progression of the cancer.

We report remote manipulation of micronanomachines containing magnetic nanoparticles. Surface-modified Fe(3)O(4) nanocrystals were synthesized as doping agents of the photopolymerizable resin, which was pinpoint written by femtosecond laser-induced two-photon photopolymerization to create microsprings. Owing to the nature of superparamagnetism of Fe(3)O(4) nanoparticles, force exerted to the microsprings relies sensitively on the field gradient of the external ferromagnet, and various motions like elongation, bending, and swing are achieved in a well-controllable remote manner. As a noncontact, sensitive, easy, and environmentally friendly approach, the magnetic driving of micronanomachines may play an important role for nano and biological applications.

A remarkable recent progress in two-photon photopolymerization is the achievement of fabrication resolution around tens of nanometers, establishing a femtosecond laser as a nanofabrication tool. However, how the superresolution has been made possible is still under arguement. We propose a concept of polymer network permeability to solvents, meaning a structure-loosened nanopolymer state that allows free penetration of small molecules to interpret the mechanism. Experimentally, we found proof showing existence of the state, including an unusually large volume shrinkage rate (>60%), shape-memory effect, a giant softness of nanospring, and the mechanical stability of rinsed two-photon written polymer nanowires.

Thanatos-associated proteins (THAPs) are zinc-dependent, sequence-specific DNA-binding factors involved in cell proliferation, apoptosis, cell cycle, chromatin modification and transcriptional regulation. THAP11 is the most recently described member of this human protein family. In this study, we show that THAP11 is ubiquitously expressed in normal tissues and frequently downregulated in several human tumor tissues. Overexpression of THAP11 markedly inhibits growth of a number of different cells, including cancer cells and non-transformed cells. Silencing of THAP11 by RNA interference in HepG2 cells results in loss of cell growth repression. These results suggest that human THAP11 may be an endogenous physiologic regulator of cell proliferation. We also provide evidence that the function of THAP11 is mediated by its ability to repress transcription of c-Myc. Promoter reporter assays indicate a DNA binding-dependent c-Myc transcriptional repression. Chromatin immunoprecipitations and EMSA assay suggest that THAP11 directly binds to the c-Myc promoter. The findings that expression of c-Myc rescues significantly cells from THAP11-mediated cell growth suppression and that THAP11 expression only slightly inhibits c-Myc null fibroblasts cells growth reveal that THAP11 inhibits cell growth through downregulation of c-Myc expression. Taken together, these suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc.

Aim: To evaluate the efficacy and safety of 3,000 mg daily levetiracetam (LEV; Keppra) as an adjunctive therapy for Chinese patients with refractory partial seizures., Methods: This randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 4-week titration interval and a 12-week maintenance period, and concluded with a 4-week medication withdrawal period or entered an open-label study. LEV was compared with placebo., Results: The 50% responder rate (the proportion of patients with a minimum of 50% reduction in partial seizure frequency) occurred in 46.4% of the LEV group, compared with 39.3% of the placebo group (p = 0.590). The median of the absolute weekly frequency reduction from baseline of partial seizures was 0.66 per week for LEV versus 0.48 per week for placebo (p = 0.187). The most common treatment-emergent adverse events, mostly mild to moderate in severity, were somnolence, dizziness and agitation., Conclusion: In this study, adjunctive therapy with LEV 3,000 mg daily was well tolerated but not as effective as expected in controlling partial seizures in this study population. Considering the lower mean weight of this study population, we suggest the dosage of LEV 3,000 mg daily may contribute to the results., (Copyright 2009 S. Karger AG, Basel.)

Three kinds of high efficiency phase-type fractal zone plates were rapidly (in tens of minutes) fabricated by femtosecond laser two-photon photopolymerization. Their theoretical maximal diffractive efficiencies of 24.5%, 12.52%, and 18.76% were predicted both by numerical simulation and analytical deduction and were verified by the measured values of 20.5%, 9.1%, and 13%, respectively. The characteristic of multifoci and the improved imaging ability for phase-type fractal lens was also demonstrated. Moreover, to further enhance the diffractive efficiency, a four-level fractal phase lens, whose diffraction efficiency reached as high as 37.6%, was proposed and realized.

Purpose: To observe the effect of three protective agents on edge closeness of glass ionomer cements filling in vitro., Methods: Eighty freshly extracted human molars were randomly divided into A and B groups(40 molars each group). The teeth cavities were prepared at 1/3 part to buccal gingiva of each molar and those of A group were filled with GC Fuji IX and those of B group with another glass ionomer cement. A and B groups were respectively divided into three experiment groups and one control group(A1/B1). The filling surfaces of three experimental groups were separately coated with vaseline(A2/B2), cocoa butter(A3/B3), biscover (A4/B4). After thermal cycling(x 30, 5-55 degrees centigrade), the depth of dye penetrating into the teeth was observed through an optical microscope. The data was analyzed with rating information on diverse groups of the rank and testing, using SPSS13.0 software package., Results: Different dye penetration degrees were shown between filling material and cavity walls among each group, while the degrees of dye penetration of experimental groups were significantly slighter than those of corresponding control group(P<0.05), and there was no difference among experimental groups (P>0.05)., Conclusion: The three protective agents can increase the edge closeness of glass ionomer cement filling.

Dammann gratings, as beam splitters and coherent signal generators, were produced in a short fabricating cycle by femtosecond laser fabrication via two-photon photopolymerization. These holograms that each generated 2x2, 3x3, 4x4, 5x5, and 6x6 spot sources in the fan-out demonstrated diffraction efficiency of 36%, 25%, 29%, 52%, and 49%, respectively, comparable with the theoretical values. This work shows the promising prospect of femtosecond laser fabrication in compatibly manufacturing various micro-optical devices including Dammann gratings and their integrated systems.

We investigated laminin beta1 expression in the hippocampi of patients with intractable epilepsy and explored the role of laminin beta1 in the pathogenesis of this condition. Fluorescence quantitative PCR, immunofluorescence, immunohistochemistry and Western blotting were used to measure laminin beta1 expression in surgically removed hippocampi of patients with intractable epilepsy, and the results were compared with control hippocampi. Fluorescence quantitative PCR showed increased expression of laminin beta1 mRNA in patient hippocampi compared with control tissues. Immunohistochemical staining demonstrated that laminin beta1 protein expression was significantly increased in patient hippocampi, and immunofluorescence microscopy showed accumulation of laminin beta1 in the cell membrane and cytoplasm of patient hippocampi. These findings were confirmed by Western blotting of protein preparations from patient hippocampi. Elevated expression of laminin beta1 mRNA and protein in the hippocampus suggests that laminin beta1 may play a role in the development of epileptic seizures in patients with intractable epilepsy.

EDAG, a hematopoietic tissue-specific protein, is involved in the regulation of proliferation, differentiation and apoptosis of hematopoietic cells. In this study, a dose-dependent inhibition of EDAG expression by PMA was observed in K562 cells. The responsive element for the PMA-induced inhibition was contained in the region between -211 and +32bp of the EDAG gene promoter. By oligonucleotide-directed mutagenesis, EMSA, ChIP and transient transfection assays, we found that two tandem repeat GATA-1 sites in the promoter of EDAG gene played an important role in the PMA-mediated down-regulation of the EDAG gene expression in K562 cells. The kinetics of EDAG expression during PMA induction showed that the levels of EDAG expression were down-regulated concomitantly with GATA-1 down-expression. Decreased GATA-1 expression by siRNA reduced expression of EDAG in K562 cells, and restored expression of GATA-1 significantly rescued EDAG expression from PMA-mediated suppression. Overexpression of EDAG in K562 cells inhibited the megakaryocytic differentiation induced by PMA which raised the interesting possibility that PMA induced K562 cells differentiation toward megakaryocytic phenotype through, at least in part, the inhibition of EDAG expression. In vivo analysis confirmed that EDAG was highly expressed in primitive progenitor cells and down-regulated in megakaryocytes which was consistent with the expression pattern of GATA-1. Furthermore, PKC and MAPK specific inhibitors treatment attenuated the down-regulation of EDAG induced by PMA. Taken together, these results suggest that the inhibition of the EDAG gene by PMA is mediated through down-regulation of transcription factor GATA-1 and involved the PKC/MAPK signaling pathway.

Objective: Study on the diagnostic accuracy of fine needle aspiration biopsy of cervical lymph nodes and to discuss the reasons of making a misdiagnosis., Methods: Five hundred and eighty cases of cervical lymph node fine needle aspiration biopsy were reviewed retrospectively. Among them, histologic findings were available in 161 cases. The cytologic and histologic diagnoses were compared., Results: There were altogether 226 cases of reactive lymphoid hyperplasia, 202 cases of specific inflammation, 45 cases of malignant lymphoma and 107 cases of metastatic carcinoma. The concordance rate between the cytologic and corresponding histologic diagnoses was 94.4%. The primary foci of most cases with metastatic carcinoma could be delineated by reviewing the clinical and pathologic finding. Inadequate cellularity was the main reason of making misdiagnosis and useful diagnostic clues might be obtained by careful study of the clinical findings., Conclusions: Fine needle aspiration biopsy of cervical lymph node carries a high diagnostic accuracy. It provides important clues in guiding subsequent clinical management. However, for detailed subtyping of certain disease entities such as malignant lymphoma, surgical biopsy for histologic and immunohistochemical studies are required.

We present the first report of two-photon induced plastic surface deformation in solid polymer films. Exposure of azo polymer films, which absorb in the visible range (lambda(max) = 480 nm), to intense 920 nm irradiation leads to polarization dependent photofluidic polymer nanomovement caused by photoselective two-photon trans <-->cis isomerization. The deformations were induced by a gradient of light intensity; and strongly depend on the wavelength and the polarization direction of the incident laser light and the position of the focused spot with respect to the plane of the polymer film.

Micronanostructures prepared by two-photon photopolymerization are utilized as templates for electroless plating of metals, giving rise to an approach for fabricating complex-shaped metal micronanostructures that are so far not achievable by other means. We show that when the coated-layer thickness of a metal coating is larger than a critical value (around 20 nm for silver at 2-3 microm wavelength) associated with the metal's skin depth, the photonic crystals exhibit optical properties more comparable to a solid metal structure than to their polymer counterparts.

Mechanical overloading is a major causative factor of tendinopathy; however, its underlying mechanisms are unclear. We hypothesized mechanical overloading would damage tendons and alter genes associated with tendinopathy in a load-dependent manner. To test this hypothesis, we fatigue loaded rat patellar tendons in vivo and measured expression of the matrix-degrading enzyme MMP-13 and the inflammatory cytokine IL-1beta. We also examined these responses in cultured tenocytes exposed to intermittent hydrostatic pressure in vitro. Additionally, we hypothesized load-induced changes in tenocyte MMP-13 expression would be dependent on expression of IL-1beta. In vivo fatigue loading at 1.7% strain caused overt microstructural damage and upregulated expression of MMP-13 and IL-1beta, while 0.6% strain produced only minor changes in matrix microstructure and downregulated expression of both MMP-13 and IL-1beta. Loading of cultured tenocytes at 2.5 and 7.5 MPa produced comparable changes in expression to those of in vivo tendon loading. Blocking IL-1beta expression with siRNA suppressed load-induced both MMP-13 mRNA expression and activity. The data suggest fatigue loading alters expression of MMP-13 and IL-1beta in tendons in vivo and tenocytes in vitro in a load-dependent manner. The data also suggest MMP-13 is regulated by both IL-1beta-dependent and IL-1beta-independent pathways.

A series of substituted phenylpyrazole[4,5-b]oleanane derivatives have been synthesized and biologically evaluated as inhibitors of glycogen phosphorylase (GP). The structure of phenylpyrazole moiety in compound 17 was determined by ROESY. All of the synthesized oleanane derivatives were biologically evaluated against rabbit muscle GPa. Within this series of compounds, pyrazole triterpene 7 (IC(50) = 10.8 μM) exhibited slightly more potent activity than its parent compound 1. Preliminary SAR analysis of the pyrazoleoleanane derivatives as GP inhibitors is discussed.

Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34+ lin- bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.

Purpose: To evaluate the cytotoxicity of new root canal filling material-composite oyster shell paste., Methods: According to the evaluated criteria of medical materials, biology and animal trials recommended in ISO 10993,the extracts of powder part and the mixture of the new material were prepared separately and selected as the experimental. The RPMI1640 subject was used as the negative control and the V79 cell as the experimental cell. The cells were cultured in extract of different thickness compound for 2,4,7 days respectively and the changes of the cells were observed under microscope.The proliferation of the cells were examined and the optical density(OD)was obtained using MTT assay. SPSS12.0 software was used for statistical analyses., Results: During all culture periods, the V79 cells showed normal morphology and proliferation increased with culture time. The OD of the experimental groups were not significantly different from that of the negative groups(P>0.05)and the OD increased as time goes on., Conclusion: The new root canal filling material shows no detected cytotoxic effect from this study.

Objective: To determine and compare the difference of cell apoptosis and proliferation in the transition and peripheral zones in the human prostate., Methods: Seventeen normal prostate glands from organ donors were sampled from normal men according to McNeal/s zonal anatomy, and 20 hyperplastic transition zones obtained from prostatectomy specimens of BPH patients. Cell proliferation and Bcl-2 expression were assessed by immunostaining using PCNA and anti-Bcl-2 antibodies, while apoptotic bodies were specifically stained using TUNEL. Bcl-2 mRNA expression was detected by RT-PCR., Results: In the normal epithelium, the rates of cell proliferation and apoptosis were markedly decreased in the transition zone as compared with the peripheral zone. The proliferation index was significantly increased in the hyperplastic transition zone in BPH, while the apoptosis index significantly decreased in comparison with the normal prostate. Bcl-2 was significantly greater in the normal transition epithelium than in the peripheral zone, and over-expressed in the hyperplastic transition zone. There was a significant negative correlation between the Bcl-2 expression and the apoptosis of the epithelial cells in the hyperplastic transition zone (r(s) = -0.867, P < 0.01)., Conclusion: The hyperplastic transition zone may result from both an increase of cell proliferation and a failure of cell apoptosis. Increased expression of Bcl-2 may participate in the BPH process by blocking cell apoptosis.

With pot experiment, this paper studied the effects of PCBs (0, 180, 900, 1800 and 2700 microg x kg(-1)) on the seedlings growth and the leaves chlorophyll content, MDA content, and membrane protective enzyme system of Aegiceras corniculatum. The results showed that PCBs had definite stimulative effects on the seedlings growth. The stem height, basal stem diameter, and stem volume were all increased with increasing PCBs concentration. Within the test range of PCBs, the chlorophyll content and chlorophyll a/b ratio maintained at a relatively stable and normal level. The decrement of chlorophyll content and the increment of chlorophyll a/b ratio were less than 25% and 10% of the control, respectively. With increasing PCBs concentration, SOD activity increased first and decreased then, while POD activity and MDA content were in adverse. It was suggested that A. corniculatum could endure and adapt definite concentrations of PCBs through physiological and biochemical mechanisms, being available to the phytoremediation of PCBs pollution.

Objective: To investigate the curative effects of different reconstruction methods in the treatment of avulsion of ureteral mucosa., Methods: Twenty adult dogs were randomly divided into 4 equal groups: Group III (control group in which the ureter was incised and a ureteral stent was placed therein), Group II (the ureter was incised and a ureteral mucosal avulsion about 5 cm in length was created and the avulsed mucosa was replaced to the original position and a ureteral stent was placed in addition), Group III (a piece of bladder mucosa was incised and grafted to the avulsed ureter mucosa and a ureteral stent was placed in addition), and Group IV (a tubularized peritoneal free graft and a ureteral stent were placed in the avulsed ureter). Ten weeks later intravenous pyelography (IVP) was conducted to observe the images of ureter. Then the dogs were killed and pathological examination of the reconstructed ureter was conducted., Results: IVP showed atresia and stenosis in all control group dogs. No obvious stenosis was observed in Groups II and IV. Pathological examination showed that the newly grown mucosa was similar to the normal ureter structure in Groups II and IV. In Group III one dog died, slight distension of ureter superior to the reconstructed part was found in 2 dogs, and no obvious stenosis was observed in 3 dogs., Conclusion: Orthotopic replacement and tabularized peritoneal free grafting with placement of ureter stent are effective in treatment of avulsion of ureter mucosa. Bladder mucosa can be used as selectable material.