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Use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with reduced risk of colorectal cancer (CRC). However, the mechanism by which NSAIDs suppress colorectal tumorigenesis remains unclear. We previously showed that NSAIDs selectively kill emerging tumor cells via death receptor (DR) signaling and a synthetic lethal interaction mediated by the proapoptotic Bcl-2 family protein BID. In this study, we found NSAIDs induce endoplasmic reticulum (ER) stress to activate DR signaling and BID in tumor suppression. Importantly, our results unveiled an ER stress- and BID-dependent immunogenic effect of NSAIDs, which may be critical for tumor suppression. NSAID treatment induced hallmarks of immunogenic cell death (ICD) in CRC cells and colonic epithelial cells upon loss of APC tumor suppressor, and elevated tumor-infiltrating lymphocytes (TILs) in the polyps of APCMin/+ mice. ER stress inhibition or BID deletion abrogated the antitumor and immunogenic effects of NSAIDs. Furthermore, increased ER stress and TILs were detected in human advanced adenomas from NSAID-treated patients. Together, our results suggest that NSAIDs induce ER stress- and BID-mediated ICD to restore immunosurveillance and suppress colorectal tumor formation.

Two new coordination polymers, [Zn(3-NDI)0.5(NDC)(DMF)]n (1) and {[Zn1.5(3-NDI)0.5(BDC)1.5]·2.5DMF}n (2), were synthesized based on naphthalenediimide and aromatic dicarboxylic acids (3-NDI = N,N′-bis (3-pyridine methyl)-1,4,5,8-naphthalenediimide, H2NDC = 1,4-naphthalenedicarboxylic acid, H2BDC = terephthalic acid, and DMF = N,N′-dimethylformamide). Complex 1 is a two-dimensional structure, whereas complex 2 is a three-dimensional structure with a hex topology. Both complexes feature photochromic behaviors, which are proved by single-crystal X-ray diffraction, UV-vis spectroscopy and EPR characterization. Furthermore, both complexes have obvious fluorescence quenching behaviors upon irradiation by using a xenon lamp.

ObjectiveThere is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need.Design and resultsA total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI −12.59 to −2.50; p=0.0018), respectively.ConclusionsThis is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group.Trial registrationNCT01770431; Post-results.

Intrinsic and acquired resistance to anti-EGFR antibody therapy, frequently mediated by a mutant or amplified KRAS oncogene, is a significant challenge in the treatment of colorectal cancer (CRC). However, the mechanism of KRAS-mediated therapeutic resistance is not well understood. In this study, we demonstrate that clinically used anti-EGFR antibodies, including cetuximab and panitumumab, induce killing of sensitive CRC cells through p73-dependent transcriptional activation of the pro-apoptotic Bcl-2 family protein PUMA. PUMA induction and p73 activation are abrogated in CRC cells with acquired resistance to anti-EGFR antibodies due to KRAS alterations. Inhibition of aurora kinases preferentially kills mutant KRAS CRC cells and overcomes KRAS-mediated resistance to anti-EGFR antibodies in vitro and in vivo by restoring PUMA induction. Our results suggest that PUMA plays a critical role in meditating the sensitivity of CRC cells to anti-EGFR antibodies, and that restoration of PUMA-mediated apoptosis is a promising approach to improve the efficacy of EGFR-targeted therapy.

Prevention or early detection is one of the most promising strategies against colorectal cancer (CRC), the second leading cause of cancer death in the US. Recent studies indicate that antitumor immunity plays a key role in CRC prevention. Accumulating evidence suggests that immunosurveillance represents a critical barrier that emerging tumor cells have to overcome in order to sustain the course of tumor development. Virtually all of the agents with cancer preventive activity have been shown to have an immune modulating effect. A number of immunoprevention studies aimed at triggering antitumor immune response against early lesions have been performed, some of which have shown promising results. Furthermore, the recent success of immune checkpoint blockade therapy reinforces the notion that cancers including CRC can be effectively intervened via immune modulation including immune normalization, and has stimulated various immune-based combination prevention studies. This review summarizes recent advances to help better harness the immune system in CRC prevention.

The expression of breast cancer resistant protein (BCRP) in lung cancer is correlated with development of multidrug resistance (MDR) and therefore leads to lower response to chemotherapy. ZM323881, a previously developed selective VEGFR-2 inhibitor, was found to have inhibitory effects on BCRP-mediated MDR in this investigation. ZM323881 significantly decreased the cytotoxic doses of mitoxantrone and SN-38 in BCRP-overexpressing NCI-H460/MX20 cells. Mechanistic studies revealed that ZM323881 effected by inhibiting BCRP-mediated drug efflux, leading to intracellular accumulation of BCRP substrates. No significant alteration in the expression levels and localization pattern of BCRP was observed when BCRP-overexpressing cells were exposed to ZM323881. Stimulated bell-shaped ATPase activities were observed. Molecular docking suggested that ZM323881 binds to the modulator site of BCRP and the binding pose is stable validated by 100 ns molecular dynamic simulation. Overall, our results indicated that ZM323881 reversed BCRP-related MDR by inhibiting its efflux function. These findings might be useful in developing combination chemotherapy for MDR cancer treatment.

Cabozantinib (XL184) is a small molecule tyrosine kinase receptor inhibitor, which targets c-Met and VEGFR2. Cabozantinib has been approved by the Food and Drug Administration to treat advanced medullary thyroid cancer and renal cell carcinoma. In the present study, we evaluated the ability of cabozantinib to modulate the function of the ATP-binding cassette subfamily G member 2 (ABCG2) by sensitizing cells that are resistant to ABCG2 substrate antineoplastic drugs. We used a drug-selected resistant cell line H460/MX20 and three ABCG2 stable transfected cell lines ABCG2-482-R2, ABCG2-482-G2, and ABCG2-482-T7, which overexpress ABCG2. Cabozantinib, at non-toxic concentrations (3 or 5 μM), sensitized the ABCG2-overexpressing cells to mitoxantrone, SN-38, and topotecan. Our results indicate that cabozantinib reverses ABCG2-mediated multidrug resistance by antagonizing the drug efflux function of the ABCG2 transporter instead of downregulating its expression. The molecular docking analysis indicates that cabozantinib binds to the drug-binding site of the ABCG2 transporter. Overall, our findings demonstrate that cabozantinib inhibits the ABCG2 transporter function and consequently enhances the effect of the antineoplastic agents that are substrates of ABCG2. Cabozantinib may be a useful agent in anticancer treatment regimens for patients who are resistant to ABCG2 substrate drugs.

Background. Prostate cancer (PCa) is the ninth most common cause of cancer death globally. Many studies have investigated aspirin exposure and mortality risk among PCa patients, returning inconsistent results. We conducted a comprehensive meta-analysis to explore the association between aspirin exposure and mortality risk among PCa patients and to investigate potential dose/duration/frequency-response relationships. Methods and Results. Studies published from 1980 to 2018 of PubMed and EMBASE databases were searched. We included 14 studies with 110,000 participants. Multivariate-adjusted odds ratios (ORs) were pooled using random-effect models. Potential dose/duration/frequency-response relationships were evaluated for aspirin exposure and prostate cancer-specific mortality (PCSM) risk. We did not detect an association between the highest aspirin exposure and mortality risk (PCSM of prediagnostic aspirin exposure, OR: 0.96, 95% confidence interval [CI]: 0.87-1. 07, I2 = 0%; PCSM of postdiagnostic aspirin exposure, OR:0.92, 95% CI: 0.77-1.10, I2 = 56.9%; all-cause mortality [ACM] of prediagnostic aspirin exposure, OR: 0.96, 95% CI: 0.88-1.04, I2 = 9.4%; ACM of postdiagnostic aspirin exposure, OR: 0.95, 95% CI: 0.73-1.23, I2 = 88.9%). There was no significant dose/frequency-response association observed for aspirin exposure and PCSM risk. On duration-response analysis, we found that short-term postdiagnostic aspirin exposure (shorter than 2.5 years) increased the risk of PCSM. Conclusions. Our meta-analysis suggests that there is no association between aspirin exposure and PCSM risk. Nor is there an association between the highest aspirin exposure and ACM risk among PCa patients. More studies are needed for a further dose/duration/frequency-response meta-analysis.

Nitric oxide (NO) is a well-known signaling molecular that plays a significant role in stress tolerance of plants to heavy metals. However, the detoxification mechanism of NO has not been well studied. Here, we examined the absorbing and transporting characteristics of copper (Cu) and cadmium (Cd) in tomato seedlings through nutrient solution culture and its response to exogenous NO under Cu and/or Cd stress. Results showed that Cu and Cd with the concentration of 50Mgr;mol·L一氧化氮(NO)作为信号分子,在抵御重金属胁迫中起重要作用,但对不同离子胁迫下的解毒机制尚缺乏研究.本研究采用营养液培养法,研究了铜(Cu)、镉(Cd)单一或复合胁迫下,番茄幼苗对Cu、Cd的吸收转运特性及对外源NO的响应机制.结果表明: 50 μmol·L

BACKGROUND Prostate cancer is a common type of malignant tumor invading the male reproductive-urinary system, which has increasing incidence worldwide. Androgen receptor variant 7 (AR-V7) participates in regulating prostate cancer cell proliferation and gene expression. This study aimed to investigate the expression of AR-V7 in circulated tumor cells (CTCs) in patients with prostate cancer and to assess its correlation with drug sensitivity against enzalutamide or abiraterone. MATERIAL AND METHODS Blood samples of prostate cancer patients were collected for separating CTCs, in which mRNA expression level of full-length AR and AR-V7 was measured to analyze their correlation with enzalutamide or abiraterone resistance. Progression-free survival (PFS) of patients with different AR-V7 expression levels was compared. AR-V7 was overexpressed in transfected prostate cancer cells, and its effects on proliferation were analyzed by clonal formation assay. RESULTS qRT-PCR showed AR-V7 overexpression in a total of 13 patients; 76.92% of these patients developed drug resistance, the distal metastasis of which was significantly higher than that in the group with AR-V7 downregulation, with lower PFS (p

Arabinoglactan protein (AGP)-rich nanoparticles obtained from the sticky exudates of Hedera helix (English ivy), have shown promising potential to be used in nanomedicine owing to their excellent aqueous solubility, low intrinsic viscosity, biocompatibility, and biodegradability. In this study, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine are evaluated. Via electrostatic and hydrophobic interactions, pH-responsive nanoconjugates are formed between the INPs and the doxorubicin (DOX) with an entrapment ratio of 77.9 ± 3.9%. While the INPs show minimal cytotoxicity, the formed INP-DOX conjugates exhibit substantially stronger cytotoxic activity than free DOX against multiple cancer cell lines, suggesting a synergistic effect is established upon conjugation. The anti-cancer effects of the INP-DOX conjugates are further evaluated via in vivo xenograft assays by subcutaneously implanting DOX resistant cell line, SW620/Ad-300, into nude mice. The tumor volumes in mice treated with the INP-DOX conjugates are significantly less than those of the mice treated with free DOX. In addition, the INPs are further exploited as nano-fillers to develop fibrous scaffolds with collagen, via mimicking the porous matrix where the INPs are embedded under natural condition. Enhanced adhesion of smooth muscle cells (SMCs) and accelerated proliferation of mouse aortic SMCs are observed in this newly constructed scaffold. Overall, the results obtained from the present study suggest great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. The AGP-rich INP renders a glycoprotein architecture that is amenable for modification according to the functional designs, capable of being developed as versatile nanomaterials for extensive biomedical applications. Statement of Significance Naturally occurring organic nanomaterials have drawn increasing interest for their potential biomedical applications in recent years. In this study, a new type of naturally occurring nanoparticles obtained from the sticky exudates on the adventitious roots of English ivy ( H. helix ), was explored for its potential biomedical application. In particular, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine were evaluated both in vitro and in vivo . Overall, the results obtained from the present study suggest the great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. This study may open a totally new frontier for exploring the biomedical application of naturally occurring nanomaterials.

One glass single ITO layer solution has been demonstrated for large size projected-capacitive touch panels. Using simple touch sensors and algorithm, the proposed solution can effectively solve the issues of sensitivity reduction and large coordinate shifting existing in current large size touch panels. A touch system based on the proposed solution can achieve a coordinate shifting of less than 1.5%.

Background This study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli . Methods This randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed. Results All but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified. Conclusion The prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy. Clinical trials registration : NCT01356823 .

A patterned inverted cone (PIC) structure on flexible substrate produced by focused femtosecond laser was demonstrated for the out-coupling efficiency enhancement of electroluminescent devices. A green Organic Light-Emitting Diode (OLED) with PIC structure on flexible substrate was employed to verify the effect of the proposed method, which exhibited a current efficiency enhancement by a factor of 2.2 at 10 mA/cm2 without any emission spectrum altered, compared with conventional flexible OLED. The PIC structure is compatible with current device fabrication process and applicable for full color OLED display and lighting.

BackgroundHepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined. MethodsIn an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years. ResultsDuring the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in ...

Background and Purpose The transporter, multidrug resistance protein 1 (MRP1, ABCC1), plays a critical role in the development of multidrug resistance (MDR). Ibrutinib is an inhibitor of Bruton's tyrosine kinase. Here we investigated the reversal effect of ibrutinib on MRP1-mediated MDR.

The phenomenon of multidrug resistance (MDR) has attenuated the efficacy of anticancer drugs and the possibility of successful cancer chemotherapy. ATP-binding cassette (ABC) transporters play an essential role in mediating MDR in cancer cells by increasing efflux of drugs from cancer cells, hence reducing the intracellular accumulation of chemotherapeutic drugs. Interestingly, small-molecule tyrosine kinase inhibitors (TKIs), such as AST1306, lapatinib, linsitinib, masitinib, motesanib, nilotinib, telatinib and WHI-P154, have been found to have the capability to overcome anticancer drug resistance by inhibiting ABC transporters in recent years. This review will focus on some of the latest and clinical developments with ABC transporters, TKIs and anticancer drug resistance.

Cancer cells often become resistant to chemotherapy through a phenomenon known as multidrug resistance (MDR). Several factors are responsible for the development of MDR, preeminent among them being the accelerated drug efflux mediated by overexpression of ATP binding cassette (ABC) transporters. Some small molecule tyrosine kinase inhibitors (TKIs) were recently reported to modulate the activity of ABC transporters. Therefore, the purpose of this study was to determine if motesanib, a multikinase inhibitor, could reverse ABCB1-mediated MDR. The results showed that motesanib significantly sensitized both ABCB1-transfected and drug-selected cell lines overexpressing this transporter to its substrate anticancer drugs. Motesanib significantly increased the accumulation of [ 3 H]-paclitaxel in ABCB1 overexpressing cells by blocking the efflux function of ABCB1 transporter. In contrast, no significant change in the expression levels and localization pattern of ABCB1 was observed when ABCB1 overexpressing cells were exposed to 3 μM motesanib for 72 h. Moreover, motesanib stimulated the ATPase activity of ABCB1 in a concentration-dependent manner, indicating a direct interaction with the transporter. Consistent with these findings, the docking studies indicated favorable binding of motesanib within the transmembrane region of homology modeled human ABCB1. Here, we report for the first time, motesanib, at clinically achievable plasma concentrations, antagonizes MDR by inhibiting the efflux activity of the ABCB1 transporter. These findings may be useful for cancer combination therapy with TKIs in the clinic.

Background ARRY-334543 is a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases. We conducted this study to determine whether ARRY-334543 can enhance the efficacy of conventional anticancer drugs through interaction with ABC transporters.

A compact light guide plate (LGP) with special designed microstructures and dual collimated light sources was proposed to achieve an adjustable riming angle backlight for eco-display. The micro-prisms were utilized to guide the emitting rays toward normal viewing cones while a set of strip patterned diffuser toward wide viewing cones. The uniformity of spatial luminous can reach 91% / 87% at view cone of ±3/±60 deg. in each mode. Only 5% of power consumption in narrow viewing angle mode was needed to keep the same luminance in wide viewing angle mode.

A novel backlight module that integrates dual layer strip patterned organic light emitting diode (DLSP-OLED) for 2D/3D switchable display was demonstrated. The DLSP-OLED functions as a parallax barrier in 3D mode and a planar light source in 2D mode. The results indicated that the backlight module with a thin form factor ( ~ 1.1 mm) can achieve uniformity of 91% in 2D mode, and increased optical efficiency by a factor of 2.8 with a crosstalk of less than 6% in 3D mode, compared with the conventional 2D/3D switchable display. A fast switching rate (

A combined fringe and in-plane switching (FIS) mode single-cell-gap transflective display using blue-phase liquid crystal (BPLC) is proposed. The structure makes use of the space above the pixel electrodes of this FIS mode as reflective regions and the space between pixel electrodes as transmissive regions. The structure which can be optimized to balance the optical phase retardation between transmissive region and reflective region with simple fabrication process exhibits relatively high optical efficiency and well matched voltage of transmittance and reflectance curves.

To preliminarily evaluate the feasibility, therapeutic effect and toxicity of stereotactic gamma-ray body radiation therapy (γ-SBRT) for asynchronous bilateral renal cell carcinoma (bRCC).A retrospective analysis was performed on the clinical data of nine patients with asynchronous bRCC who were unable to undergo surgery and received γ-SBRT between February 2002 and May 2012. A total dose of 36-51 Gy was delivered to the 50 % isodose line covering the planning target volume at 3-5 Gy/fraction, whereas a total dose of 60-85 Gy was delivered at 5-7 Gy/fraction to the gross target volume. The local control rate (LC) and overall survival rate (OS) were calculated using the Kaplan-Meier method.Patient follow-up ended in March 2013 and the follow-up rate was 100 %. Of the nine patients, none presented with complete remission and five (55.6 %) achieved partial remission. The objective response rate was 55.6 %. The 1-, 3- and 5-year LC rates were 64.8, 43.2 and 43.2 %, respectively. The 1-, 3- and 5-year OS rates were 66.7, 53.3 and 35.6 %, respectively. Four (44.4 %) patients had an acute radiation reaction; there were two cases of grade I leukocytopenia and two cases of grade I gastrointestinal reactions. Late radiation-induced toxicity consisted of grade II gastrointestinal reactions in two patients.Stereotactic gamma-ray body radiation therapy was found to be safe and effective in the treatment of asynchronous bRCC. Improved prognosis will require individualised treatment and a combination of multiple therapeutic approaches; this will be a primary research trend in the future.

P-glycoprotein (P-gp) serves as a therapeutic target for the development of multidrug resistance reversal agents. In this study, we synthesized 21 novel compounds by peptide coupling at corresponding carboxyl and amino termini of (S)-valine-based bis-thiazole and monothiazole derivatives with diverse chemical scaffolds. Using calcein-AM efflux assay, we identified compound 28 (IC50 = 1.0 μM) carrying 3,4,5-trimethoxybenzoyl and 2-aminobenzophenone groups, respectively, at the amino and carboxyl termini of the monothiazole zwitter-ion. Compound 28 inhibited the photolabeling of P-gp with [(125)I]-iodoarylazidoprazosin with IC50 = 0.75 μM and stimulated the basal ATP hydrolysis of P-gp in a concentration-dependent manner (EC50 ATPase = 0.027 μM). Compound 28 at 3 μM reduced resistance in cytotoxicity assay to paclitaxel in P-gp-expressing SW620/Ad300 and HEK/ABCB1 cell lines. Biochemical and docking studies showed site-1 to be the preferable binding site for 28 within the drug-binding pocket of human P-gp.

A novel fabrication method using holographic exposure for switchable blue phase (BP) liquid crystal (LC)/polymer Fresnel lens was demonstrated. The Fresnel pattern can be achieved by interfering a planar and a spherical wave fronts with a 532-nm laser. The BPLC/polymer Fresnel lens can thus be fabricated without photo mask and controlled with a simpler driving compared with the conventional LC Fresnel lens.

New phenstatin-fatty acid conjugates have been synthesized and tested against the KB-3-1, H460, MCF-7 and HEK293 cell lines, with an increase in anti-proliferative activity being observed at the micro-molar level paralleling an increase in un-saturation in the fatty acid component.

For the purpose of improving the resultant performance processes of microsurface precise grinding in different machining conditions, the obtained grinded surface should be quality-evaluated and influence-assessed under the instructions of topography modeling. Since microsurface fitting algorithms exerts a considerable influence on those constructed topography mathematical features in geometric domain, which results to different grinding micro-topography processes caused by one specific influence mechanism, and makes the performance investigation of fitting algorithms in surface micro-topography grinding processes indispensable. Through extracting the coordinate positions of those selected physical control points in one objective surface topography sample to be grinded by using a series of precise spatial coordinate measurement apparatuses, several typical algorithms of surface fitting in geometric domain were used for constructing the micro-topography models of those sample section surface with complicated point cloud. On the base of computing the newly proposed mathematical features caused from those micro-topography models, fuzzy evaluation data sequences were established and one new multi-dimensional mathematical quantitative evaluation method derived from fuzzy relation set was proposed and employed to deal with their inherent mutual-relationships. As the performance comparisons of resultant grinded topography between using surface modeling operations and not using surface modeling operations were clearly quantified, it is obvious that the multi-dimensional fuzzy influence relation set between surface fitting algorithms, topography geometric features, and practical grinding processes in different experimental conditions will be quantitatively analyzed in detail, which contributes to the acquirement of final conclusions concerned with the inherent influence mechanism and mutual mathematical relation set emerged from the performance results of different surface fitting algorithms, together with the topography spatial features and practical surface grinding process characteristics in one specific experimental conditions as well. Through realizing grinding processes evaluation based on multi-dimensional fuzzy relation set and making performance comparisons with several other typical statistical evaluation methods in index analysis, an in-depth performance inspection of surface precise grinding with objective micro-topography will be facilitated and optimized; simultaneously, a new research idea for improving microsurface modeling and its subsequent grinding processes in a practical experimental operation can also be demonstrated in the long run.

A novel highly collimated backlight module transforming a point light source into a planar light source by means of a double wedge-shaped light-guide plate (LGP) was designed. The uniformity of spatial luminous can reach 80.5% at view cone of ±1.8 deg. The Gray-half-tone technology can be used to fabricate the microstructures for mass productions.

The purpose of the study was to evaluate and compare the clinical values of tension-free vaginal tape (TVT), tension-free vaginal tape-transobturator (TVT-O), or tension-free vaginal tape-Secur (TVT-Secur) as treatment for female stress urinary incontinence.The pre-operative and 1-year post-operative follow-up protocols for patients who were treated with serial mid-urethral tension-free tape procedures in two hospitals from October 2008 to December 2009 were prospectively studied. These patients were randomly allocated to TVT, TVT-O, or TVT-Secur.A total of 102 women participated. At the 1-year follow-up, complications were not statistically different across the three groups except for pain in the thigh, which was more common in the TVT-O group. The overall efficacy and cure rate were similar between the TVT and TVT-O groups, but were significantly lower in the TVT-Secur group.A comparison of the three procedures shows that TVT-O is easy to operate and is as safe as TVT-Secur, and it has similar long-term efficacy to TVT, though, as one of the third-generation mid-urethral tension-free tapes, TVT-Secur is still being evaluated. Basing on the outcome of our study, it had rare complications but unsatisfactory efficacy, and we suggest that TVT-Secur is not fit for severe cases. However, observation and comparison of these groups in a larger sample size on a longer term are needed.

A simple one glass solution with just a single layer of sensors for projected-capacitive touch panels has been proposed. It can effectively solve the coordinate shifting existing in touch panels with just a single layer of triangular sensors, thus of great potential for large size touch panels.

Objective This study was aimed to identify the specific methylation profile in bile specimens of pancreaticobillary diseases for differential diagnosis of malignant biliary stricture. Design and methods In a total of 80 bile specimens from pancreaticobillary diseases, the methylation status of 19 tumor suppressor genes were analyzed by methylation-specific PCR and the methylation index (MI) were compared between the malignant and benign groups. Results Methylation of DKK3, p16, SFRP2, DKK2, NPTX2 and ppENK were more frequently detected in the bile of malignant biliary strictures than benign patients. When setting MI 0.5 as the threshold, this 6-gene panel could distinguish the malignant biliary stricture with a high sensitivity, specificity and accuracy (77.27%, 77.78% and 77.50%, respectively). Conclusion The methylation profile including 6 specific genes in bile may be a promising biomarker for differential diagnosis between malignant and benign biliary strictures.

The persistence of covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) in hepatocytes plays a key role in viral persistence and resistance to therapy. Therefore, quantitative cccDNA measurement is of clinical importance for evaluating the efficacy of antiviral drugs, selecting an appropriate treatment strategy, and predicting the prognosis. Current established methods for measurement of cccDNA need further improvement. A modified method was developed using digestion with restriction endonucleases that do not recognize sites in the HBV DNA and plasmid-safe ATP-dependent DNase (PSAD), and using a cccDNA-specific primer set in a real-time PCR reaction. The cccDNA-specific primer has a similar amplification efficiency as a commercial kit. Treatment of samples with restriction endonuclease followed by PSAD digestion increased significantly the specificity of a cccDNA-selective primer set compared with other treatments (P

Field cancerization currently described the theory of tumorigenesis and, until now, has been described in almost all organ systems except in liver. For this reason, we explore the presence of field cancerization in liver and its underlying clinical implication in hepatocellular carcinoma (HCC). In our study, methylation profile of HCC and surgically resected margin (SRM) were established by methylation-specific PCR. Liver cirrhosis (LC), chronic hepatitis and normal liver were treated in the same way as the background control. The correlation analysis among the methylation profile of HCC, SRM and clinicopathological data of HCC patients was made respectively. Our results showed that methylation abnormities related to HCC, but not background disease existed in histologically negative SRM. Monoclonal and polyclonal models may coexist in field cancerization in liver. Patients with RIZ1 methylation in SRM had a shorter disease free survival. The local recurrence trend of early and later recurrence in HCC is potentially related to a second field tumor. From these results, we can suggest that field cancerization exists in liver. The study of field cancerization in liver plays an important role in hepatocarcinogenesis. Second field tumor derived form field cancerization may have important implications in HCC prognosis assessment that is worthy of further study.