Search

The effective one-component plasma (EOCP) model has provided an efficient approach to obtaining many important thermophysical parameters of hot dense matter [J. Clérouin, et al., Phys. Rev. Lett. 116, 115003 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.115003]. In this paper, we perform extensive quantum molecular dynamics (QMD) simulations to determine the equations of state, ionic structures, and ionic transport properties of neon and krypton within the warm dense matter (WDM) regime where the density (ρ) is up to 12 g/cm^{3} and the temperature (T) is up to 100 kK. The simulated data are then used as a benchmark to explicitly evaluate the EOCP and Yukawa models. It is found that, within present ρ-T regime, the EOCP model can excellently reproduce the diffusion and viscosity coefficients of neon and krypton due to the fact that this model defines a system which nearly reproduces the actual physical states of WDM. Therefore, the EOCP model may be a promising alternative approach to reasonably predicting the transport behaviors of matter in WDM regime at lower QMD computational cost. The evaluation of Yukawa model shows that the consideration of the energy level broadening effect in the average atom model is necessary. Finally, with the help of EOCP model, the Stokes-Einstein relationships about neon and krypton are discussed, and fruitful plasma parameters as well as a practical ρ-T-dependent formula of the effective coupling parameter are obtained. These results not only provide valuable information for future theoretical and experimental studies on dense neon and krypton but also reveal the applicability of the EOCP model and the limitation of the Yukawa model in WDM regime and further support the continuing search for a unified description of ionic transport in dense plasma.

Aim: To assess the reproducibility of a semiautomatic quantification tool for cervical stiffness and evaluate the normal changes in cervical elasticity during the three trimesters of pregnancy., Methods: This longitudinal prospective pilot study evaluated cervical elasticity during the three trimesters of pregnancy (11-14, 20-24 and 28-32 weeks) in women with singleton pregnancies. Women with a history of conization, cerclage, cervical Naboth cysts (diameter > 10 mm), cervical tumors, or uterine malformation were excluded. A semiautomatic tool was used to evaluate the stiffness of the whole cervix and the internal and external cervical os with multiple quantitative elasticity parameters and the cervical length (CL) on the sagittal view via transvaginal elastography. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess intra- and interobserver variability. E-Cervix parameters during the three trimesters were compared using the Friedman test., Results: In total, 217 women with 651 strain examinations during the three trimesters were included. The intra- and interobserver ICC for the E-Cervix parameters ranged from 0.947 to 0.991 and 0.855 to 0.989, respectively. There were significant differences in all parameters among the three trimesters. Cervical elasticity showed significant softening and became heterogeneous during the three trimesters. The median CL was significantly shorter in the first trimester than in the second and third trimesters (P = 0.004, P < 0.001)., Conclusion: E-Cervix provides a graphical tool for operators to easily define regions of interest and obtain multiple repeatable measures of elasticity. The normal references for E-Cervix parameters during the three trimesters reflect the physiological cervical changes during pregnancy., (© 2019 Japan Society of Obstetrics and Gynecology.)

We present the results of theoretical studies of formation and evolution of the current sheet in a colliosionless plasma during magnetic reconnection in relativistic limit. Relativistic magnetic reconnection is driven by parallel laser pulses interacting with underdense plasma target. Annihilation of laser created magnetic field of opposite polarity generates strong non-stationary electric field formed in between the region with opposite polarity magnetic field accelerating charged particles within the current sheet. This laser-plasma target configuration is discussed in regard with the laboratory modeling of charged particle acceleration and gamma flash generation in astrophysics. We present the results of 3-dimensional kinetic simulations and theoretical studies on the formation and evolution of the current sheet in a collisionless plasma during magnetic field annihilation in the ultra-relativistic limit. Annihilation of oppositively directed magnetic fields driven by two laser pulses interacting with underdense plasma target is accompanied by an electromagnetic burst generation. The induced strong non-stationary longitudinal electric field accelerates charged particles within the current sheet. Properties of the laser-plasma target configuration are discussed in the context of the laboratory modeling for charged particle acceleration and gamma flash generation in astrophysics.

Objective: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia., Design: Prospective multicentre study., Setting: Tertiary hospitals., Participants: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated., Main Outcome Measures: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience., Results: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement., Conclusion: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists., (© 2019 John Wiley & Sons Ltd.)

Extensive quantum molecular dynamics (QMD) simulations are performed to determine the equation of state, sound velocity, and phase diagram of middle-Z krypton in a warm dense regime where the pressure (P) is up to 300 GPa and the temperature is up to 60 kK. The shock wave experimental data are used to validate the present theoretical models. It is found that, within the regime of the current density (ρ) and temperature (T), sound velocity can effectively discriminate differences between different theoretical models, and therefore it is more suitable as a benchmark to verify the practicability of models. The QMD-simulated results of the ionic structures and electronic properties imply the occurrence of two kinds of phase transitions, including transition from a solidlike to fluid state and that from an insulator to conductive fluid in this T-P regime. The calculated electrical conductivities confirm that the metallization transition occurs at about 60 GPa and 17.5 kK along the principal Hugoniot. With the help of simulation results and experimental data, a comprehensive phase diagram for krypton is constructed by using the solid-fluid and insulator-metal fluid phase boundaries, which fills the gap of the experimental work [Proc. Natl. Acad. Sci. USA 112, 7925 (2015)PNASA60027-842410.1073/pnas.1421801112]. These results will provide an instructive basis for the experimental investigations of rare gases over a wide T-P range.

Objective: To explore the efficacy of bilateral sagittal cross percutaneous kyphoplasty(PKP) for preventing recurrent fracture of the cemented vertebrae., Methods: From January 2017 to June 2017, 85 patients with single-segment osteoporotic vertebral compression fractures(OVCFs) were treated by bilateral sagittal cross PKP(cross group). There were 35 males and 50 females with an average age of (70.1±8.3) years old in cross group. Another 85 patients with single-segment OVCFs were treated by traditional PKP (traditional group). There were 37 males and 48 females with an average age of (73.3±9.5) years old in traditional group. The cement distribution condition, recurrent fracture of the cemented vertebrae, the anterior vertebral body height and sagittal Cobb angle, visual analogue scale(VAS) were observed in two groups., Results: All patients underwent operation successfully. The follow-up time were (11.8±4.5) months in cross group and (12.1±3.7) months in traditional group. In cross group, all patients' bone cement touched the upper and lower endplates of the vertebral body while 67 cases (78.8%) in traditional group did with significant difference between two groups ( P <0.05). No patient in cross group suffered recurrent fracture of the cemented vertebrae while 10 cases (11.8%) in traditional group did with significant difference between two groups( P <0.05). The anterior vertebral body height, sagittal Cobb angle and VAS in both groups were obvious improved at 2 days after operation ( P <0.05) and there were no significant difference between two groups at 2 days after operation and the final follow-up( P >0.05)., Conclusions: Bilateral sagittal cross PKP was a simple, safe and effective technique which can make bone cement distribute in the fractured vertebral body and contact the upper and lower endplates of the vertebral body, thus preventing the recurrent fracture of the cemented vertebrae., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: The 3D model of lumbar spine was established by using Mimics software. To observe the applicability and needling parameters of lumbar vertebral kyphoplasty with unilateral puncture by backward rotation method using simulated puncture., Methods: Twenty-four patients (12 males and 12 females) with osteoporotic thoracic fracture in the first time and no signs of lumbar misalignment and bone destruction were scanned by spiral CT on the lumbar spine. The original DICOM file was modeled in 3D with Mimics software, and the vertebral bodies were separated. After being imported into 3-matic software, the posterior wall of the vertebral body was restrained for standardized measurement. A sketch perpendicular to the mid-section of the pedicle and the posterior wall of the vertebral body was drawn. The simulated puncture was performed on the sketch. The angle and distance parameters of the range of motion of the puncture needle were recorded, and the puncture needle was recorded at the top. The crossing points of the anterior, middle and posterior zones of the tangential line of the vertebral body were located at the high extraversion angle, and the results were compared and analyzed., Results: All the data in the left and right sides had no significantly differences( P >0.05). Data of different segments in different gender were significantly differences( P <0.05). The maximal extraversion angle in lumbar spine increased gradually from (33.41±1.31) degree to (56.53±4.71) degree in males, as same as in females from(28.58±2.55) to (53.86±2.68) degree. There was no crossing point in area A, 3.3% of males and 26.67% of females in area B, rest in area C. The distribution areas on gender showed statistically significance ( P <0.05)., Conclusions: Backward rotation method can theoretically meet the requirements of puncture point for vertebral compression fracture, especially for males and lower lumbar spine. The determination of the maximum inclination angle is of guiding significance to the backward rotation method., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

The origin of the North American Cordillera and its affinity with the bounding craton are subjects of contentious debate. The mechanisms of orogenesis are rooted in two competing hypotheses known as the accretionary and collisional models. The former model attributes the Cordillera to an archetypal accretionary orogen comprising a collage of exotic terranes. The latter, less popular view argues that the Cordillera is a collisional product between an allochthonous ribbon microcontinent and cratonic North America. Here we present new seismic evidence of a sharp and structurally complex Cordillera-craton boundary in the uppermost mantle beneath the southern Canadian Cordillera, which can be interpreted as either a reshaped craton margin or a Late Cretaceous collisional boundary based on the respective hypotheses. This boundary dips steeply westward underneath a proposed (cryptic) suture in the foreland, consisent with the predicted location and geometry of the mantle suture, thus favoring a collisional origin.

Objective: To explore the clinical efficacy of electroacupuncture nerve stimulation therapy (ENST) for interstitial cystitis/painful bladder syndrome (IC/PBS)., Methods: A total of 68 patients with IC/PBS were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the observation group were treated with ENST; abdominal four acupoints and sacral four acupoints were connected with a pair of electrodes and treated alternately every other day. The ENST was given 50 min per times, three times a week for 3 months. The patients in the control group were treated with perfusion therapy of four-medication combination (heparin sodinm, lidocaine, sodium bicarbonate, gentamicin sulfate), twice a week for the first 6-8 weeks, followed by twice per month for 3 months. The infusion fluid remained for 1 h before discharging. The O' Leary-Sant score, including interstitial cystitis symptom index (ICSI) and interstitial cystitis problem index (ICPI), 24 h urination frequency, visual analogue scale (VAS) and maximum bladder volume were observed before treatment and treatment of 1 month, 3 months and 6 months after treatment respectively; the adverse events during the treatment were also recorded., Results: Compared before treatment, the O'Leary-Sant score (ICSI, ICPI), 24 h urination frequency, VAS and maximum bladder volume in the two groups were improved after 1, 3 months treatment and 6 months after treatment (all P <0.05). The scores of ICSI, ICPI, VAS and 24 h urination frequency in the observation group were significantly lower than those in the control group ( P <0.05). The maximum bladder volume in the observation group was significantly higher than that in the control group ( P <0.05). Six months after treatment, the total effective rate in the observation group was 87.5% (28/32), which was higher than 69.7% (23/33) in the control group ( P <0.01). No significant adverse events occurred during the treatment., Conclusion: ENST could effectively relieve the clinical symptoms of IC/PBS, but its long-term efficacy needs further observation.

Underwater quantum key distribution (QKD) has potential applications in absolutely secure underwater communication. However, the performance of underwater QKD is limited by the optical elements, background light, and dark counts of the detector. In this paper, we propose a modified formula for the quantum bit error rate (QBER), which takes into account the effect of detector efficiency on the QBER caused by the background light. Then we calculate the QBER of the polarization encoding BB84 protocol in Jerlov-type seawater by analyzing the effect of the background light and optical components in a more realistic situation. Finally, we further analyze the final key rate and the maximum secure communication distance in three propagation modes, i.e., upward, downward, and horizontal modes. We find that secure QKD can be performed in the clearest Jerlov-type seawater at a distance of hundreds of meters, even in the worst downward propagation mode. Specifically, by optimizing the system parameters, it is possible to securely transmit information with a rate of 67 kbits/s at a distance of 100 m in the seawater channel with an attenuation coefficient of 0.03/m at night. For practical underwater QKD, the performance can also be improved by using decoy states. Our results are useful for long-distance underwater quantum communication.

We carry out a detailed study on underwater ghost imaging (GI) in oceanic turbulence. We set up a physical model of GI through oceanic turbulence, which includes light-field transmission, and interaction between light field and oceanic turbulence without considering the effects of water absorption and scattering of light. We obtain theoretical expressions for the impulse response function and the visibility of GI in oceanic turbulence based on the power spectrum of the turbulence and the extended Huygens-Fresnel integral. The results show that the quality of GI under the effects of oceanic turbulence is related to the intensity of turbulence and the propagation distance of light. The quality of GI could be maintained at a relatively small distance in strong oceanic turbulence, whereas the quality is degraded dramatically at a relatively long distance in strong oceanic turbulence. We further analyze the quality of GI under various turbulence conditions and over different propagation distances by numerical calculation. Our results provide guidance for the realization of adaptive underwater optical GI over different length scales under the effect of oceanic turbulence.

Background: Increasing the size of the central veins is required to increase the success rate of central line placement and decrease complication risk. Right-sided approach for the central veins, Valsalva maneuver, and Trendelenburg position have been recommended, but these may not be available for some cases. This study aimed to determine a more convenient patient position that can result in the largest central vein diameter., Methods: Recruited subjects were placed in 60° and 30° upper body elevation, supine position, and 30° and 60° lower body elevation, and lumbar elevation (LE) was consecutively performed, with one position maintained for 10 min. Diameters of the subclavian vein (SCV) and internal jugular vein (IJV) were measured using high-resolution two-dimensional ultrasonography at each position., Results: The most suitable position on the ordinary bed for increasing central vein diameter was LE. The maximum and minimum SCV and IJV diameters in LE were significantly larger than those in the supine position (SCV: coefficients -0.633 and -0.863, p = 0.08 and 0.011, respectively; IJV: coefficients -1.09 and -1.15, p < 0.001 and = 0.001, respectively). Leg elevation for 10 min failed to dilate the central vein diameter., Conclusion: The LE without leg elevation produced a greater and more significant increase in central vein diameter than the supine position and may be useful for central line placement., (Copyright © 2018 Elsevier Inc. All rights reserved.)

[This corrects the article DOI: 10.18632/oncotarget.18138.].

Peculiar behavior is found in a Si cluster ion, moving with a speed of ∼0.22c (c: speed of light) in a solid Al plasma in the context of cluster-ion beam driven inertial confinement fusion: The Si ion, moving closely behind the forward-moving Si ion for a distance of several Å in the cluster, feels the wake field generated by the forward Si. The acceleration interaction force on the rear Si ion by the forward-moving ion may balance with the deceleration backward force in the longitudinal-moving direction. The forward-moving Si ion would be decelerated, as an isolated ion is decelerated without correlation. However, the deceleration of the rear Si ion, moving behind closely, would be reduced significantly. The rear Si ion may catch up and overtake the forward-moving Si ion in the cluster during the Si cluster-ion interaction with the high-density Al plasma. This peculiar behavior appears when the ions are aligned well longitudinally. The wake field is confined around the Si ion in the forward and transverse directions for a distance smaller than the Si cluster interionic distance l&#95;{c}. However, the tail of the wake field extends beyond l&#95;{c} due to the Si ion high speed of ∼0.22c. Therefore, the peculiar behavior shown above appears only for the ions in one cluster aligned well longitudinally.

The acidic microenvironment of tumor tissues has been proven to be a major characteristic for differentiation from normal tissues, thereby providing a desirable target for both disease diagnosis and functional imaging. We herein introduce a way to endow gold nanoparticles with aggregation behaviour induced by pH tuning. The nanoparticle surface was modified with two thiol conjugate molecules, which could smartly stabilize it at the pH of blood and normal tissues but induce aggregation in response to the acidic extracellular pH in tumor. The surface conjugate molecule composition effect was studied systematically, and at the optimal surface conjugate molecule composition, a pH-responsive active tumor-targeting c(RGDyk)-MHDA/LSC@AuNP nanoprobe was successfully obtained and showed a significantly enhanced contrast effect for both in vitro and in vivo photoacoustic (PA) imaging. Intravenous administration of our nanoprobe to U87MG tumor-bearing nude mice showed PA imaging contrasts almost 3-fold higher than those for the blocking group. Quantitative biodistribution data revealed that 9.7 μg g -1 of nanoprobe accumulated in the U87MG tumor 4 h post-injection. These findings might provide an effective strategy for developing new classes of intelligent and biocompatible contrast agents with a high efficiency for PA imaging and PA imaging-guided cancer therapy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for celastrol is still unclear. As celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both celastrol and PA could bind MD2, and that celastrol could expel PA from cells. Finally, celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2., (© 2018 Wiley Periodicals, Inc.)

Objective: Type 2 diabetes mellitus is increasing in young adults, and greater adiposity is considered a major risk factor. However, whether there is an association between obesity and diabetes and how this might be impacted by age is not clear. Therefore, we investigated the association between body mass index (BMI) and diabetes across a wide range of age groups (20-30, 30-40, 40-50, 50-60, 60-70 and ≥70 years old)., Design: We performed a retrospective cohort study using healthy screening programme data., Setting: A total of 211 833 adult Chinese persons >20 years old across 32 sites and 11 cities in China (Shanghai, Beijing, Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, Nantong) were selected for the study; these persons were free of diabetes at baseline., Primary and Secondary Outcome Measures: Fasting plasma glucose levels were measured and information regarding the history of diabetes was collected at each visit. Diabetes was diagnosed as fasting plasma glucose ≥7.00 mmol/L and/or self-reported diabetes. Patients were censored at the date of diagnosis or the final visit, whichever came first., Results: With a median follow-up of 3.1 years, 4174 of the 211 833 participants developed diabetes, with an age-adjusted incidence rate of 7.35 per 1000 persons. The risk of incident diabetes increased proportionally with increasing baseline BMI values, with a 23% increased risk of incident diabetes with each kg/m 2 increase in BMI (95% CI 1.22 to 1.24). Across all age groups, there was a linear association between BMI and the risk of incident diabetes, although there was a stronger association between BMI and incident diabetes in the younger age groups (age×BMI interaction, p<0.0001)., Conclusions: An increased BMI is also independently associated with a higher risk of developing diabetes in young adults and the effects of BMI on incident diabetes were accentuated in younger adults., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With the rising demands for pancreas transplantation, surgeons are trying to extend the donors pool and set up a more appropriate assessment system. We aim to evaluate the effect of donor hypertension on recipient overall and graft survival rates., Methods: Twenty-four thousand one hundred ninety-two pancreas transplantation patients from the Scientific Registry of Transplant Recipients database were subdivided into hypertension group (HTN, n = 1531) and non-hypertension group (non-HTN, n = 22,661) according to the hypertension status of donors. Recipient overall and graft survival were analyzed and compared by log rank test, and hazard ratios of predictors were estimated using Cox proportional hazard models., Results: Patient overall and graft survival of non-HTN group were higher than that of the HTN group (both p < 0.001). The duration of hypertension negatively influenced both overall and graft survival rates (both p < 0.001). Multivariate analyses demonstrated that hypertension was an independent factor for reduced survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.01-1.18; p < 0.001). Other independent factors included recipient body mass index (HR, 1.02; 95% CI, 1.01-1.05; p < 0.001) and transplant type (pancreas after kidney transplants / pancreas transplant alone vs. simultaneous pancreas-kidney transplants; HR, 1.41; 95% CI, 134-1.55; p < 0.001)., Conclusions: Donor hypertension is an independent factor for recipient survival after pancreas transplantation and could be considered in donor selection as well as post-transplant surveillance in clinical practice.

Objective: To explore the association between tea consumption and cognitive impairment (CoI)., Methods: 4579 adults (≥60 years) from the Weitang Geratric Diseases Study were assessed for characteristics of tea consumption and cognitive function by administering questionnaires and the Abbreviated Mental Test (AMT), respectively. We divided the subjects into normal cognitive function group (AMT score ≥8) and CoI group (AMT score ≤7).   The association between tea consumption and risk of CoI was determined by logistic regression models., Results: The least-squared means of the AMT scores for the subjects who seldom consumed tea were less favorable than those who habitually consumed tea. An inverse association was found between tea consumption (of any type) and prevalence of CoI (odds ratio = 0.74, 95% confidence interval = 0.57-0.98, P = 0.032). Interestingly, the protective correlation of tea was more obvious in never smokers (odds ratio = 0.63), but vanished in current/former smokers (odds ratio = 1.10). In never smokers, frequency of tea consumption was significantly associated with CoI (P for trend = 0.010)., Conclusion: Habitual tea consumption is suggested to be associated with a decreased risk of CoI among elders in Suzhou, and a higher frequency of tea consumption was associated with a lower prevalence of CoI among never smokers.

A mechanism for high energy γ-photon generation based on laser-plasma accelerator is proposed. The laser pulse with a peak intensity of 10 22 W/cm 2 accelerates the electron beam to GeV by the laser wakefield effect. A solid Aluminium target serves as a plasma mirror which is located at the rear side of a gas jet and reflects the laser pulse. High order harmonics are generated due to the Doppler effect experienced by the incident laser. The collisions of the reflected attosecond pulses and the energetic electron beam provide a large cross section for nonlinear Compton scattering and produce a collimated γ-photon flux. The mechanism generates GeV photons with a pulse duration given by the duration of the electron beam.

The study explores whether miR-139-5p targeting LPAR4 affects epithelial-mesenchymal transition (EMT) and fibrosis in post-menopausal women with interstitial cystitis (IC) via the PI3K/Akt signaling pathway. Bladder tissues of IC and normal bladder tissues were collected. The pathology of bladder tissues was observed by HE, Masson and Picrosirius red staining. LPAR4 positive expression rate were determined by IHC. ELISA was performed to detect the levels of IL-6, IL-8, IL-10, and TNF-α. Rat IC models were randomized into seven different groups. miR-139-5p, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, P13K, Akt, E-cadherin, N-cadherin, Vimentin, TGF-β1, and CTGF expression were determined by RT-qPCR and Western blotting. Dual luciferase reporter gene assay verified that LPAR4 is a target gene of miR-139-5p. Fibrosis was a pathological manifestation of IC. The IC group showed higher LPAR4, PI3K, Akt, p-PI3K, p-Akt, N-cadherin, Vimentin, TGF-β1, and CTGF expression but lower miR-139-5p and E-cadherin expression than the normal group. The levels of IL-6, IL-8, IL-10, and TNF-α expression decreased while HB-EGF increased in the IC group in comparison of the normal group. Compared with the blank and NC groups, E-cadherin expression was increased in the miR-139-5p mimic and siRNA-LPAR4 groups, while LPAR4, PI3K, Akt, p-P13K, p-Akt, N-cadherin, Vimentin, TGF-β1, and CTGF expression were decreased. An opposite trend was found in the miR-139-5p inhibitor group. The miR-139-5p decreased in the miR-139-5p inhibitor + siRNA-LPAR4 and miR-139-5p inhibitor + wortmannin groups. Conclusively, miR-139-5p targeting LPAR4 inhibits EMT and fibrosis in post-menopausal IC women through the PI3K/Akt signaling pathway., (© 2017 Wiley Periodicals, Inc.)

Objective: Cancer patients with bone marrow metastases are rare and dismal. The study was to identify the clinical features and prognostic factors in cancer patients with bone marrow metastases., Patients and Methods: A total of 30 patients with bone marrow metastases were reviewed between September 2007 and September 2013. Bone marrow metastases were identified by bone marrow aspiration., Results: The median age was 56.5 years (range, 8-85 years). The two most common primary tumor sites were the stomach (7, 23.3%), breast (5, 16.7%). Bone metastases (27, 90.0%) were the most common concurrent metastases. The most common cause for bone marrow aspiration was anemia and thrombocytopenia (10, 33.3%). The median survival time was 3 months (range, 0.5-82 months). Patients with good performance status (n = 19) had a longer median survival time than patients with poor performance status (n = 11) (8 months vs. 1 months, P = 0.041). Patients with primary unknown origin (n = 5) had a significantly shorter overall survival time than patients with known origin (n = 25) (1 month vs. 6 months = 0.010). The median survival time was 9 months in the systemic therapy group (n = 21) and 1 month in the best supportive care group (n = 9) (P = 0.000)., Conclusion: To make primary origin clear and start systemic antitumor therapy is beneficial for patients with bone marrow metastases., Competing Interests: There are no conflicts of interest

A new type of magnetic metal chelating carrier (PCMM-IDA-Cu 2+ ) was prepared for the immobilization of papain, using chitosan as raw material, nano Fe 3 O 4 as magnetic material, SiO 2 as porogen, iminodiacetic acid (IDA) as a chelating ligand, and binding with transition metal ion (Cu 2+ ). The resulting products were well characterized by optical microscopy, scanning electron microscopy (SEM), vibrating sample magnetometer (VSM), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The BBD (Box-Behnken Design) of RSM (Response Surface Methodology) was applied to analyze the optimum enzyme immobilization conditions. The results showed that the enzyme immobilization capacity was 94.18mg/g of PCMM-IDA-Cu 2+ , with 7.976U/mg of relative immobilized enzyme activity under the optimum conditions (pH6.73, 1.56mg enzyme/15.0mg carrier, 30.9°C), and the recovery of enzyme activity was reached 87.21%. Compared with the free papain, the immobilized papain displayed enhanced enzyme activity, superior enzymatic properties, good operational stability and reusability. It is worth mentioning that the novel carriers exhibited selectively biological adsorption capacity, and this technique is an alternative method for the immobilization of enzyme, making the process more efficient and economic., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the invasive phenotype and become migratory, which is required for cancer progression and metastasis. In the present study, the expression of EMT-associated biomarkers and their association with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC) was investigated. E-cadherin, N-cadherin, β-catenin and zinc finger E-box binding homeobox 2 (ZEB2) protein expression was evaluated with immunohistochemistry in a cohort of 76 patients with operable LSCC. The association between these transition markers, clinicopathological parameters and their prognostic impact in LSCC was analyzed. Immunohistochemical analysis revealed that EMT-associated proteins were differentially expressed between LSCC and adjacent non-neoplastic laryngeal tissue. Negative E-cadherin expression and positive N-cadherin, β-catenin and ZEB2 expression were associated with a later tumor (T) stage, decreasing tumor differentiation and a reduced overall survival (OS) time (OS: E-cadherin, P=0.016; N-cadherin, P=0.003; β-catenin, P=0.002; ZEB2, P=0.0003). E-cadherin/β-catenin co-expression was significantly associated with the majority of clinicopathological parameters assessed, including lymph node metastases, T stage and tumor cell differentiation (P=0.004, P=0.005, and P<0.001, respectively). Multivariate analysis indicated that T stage and the positive expression of β-catenin and ZEB2 were independent risk factors for OS in LSCC (P=0.014, P=0.025 and P=0.003, respectively). It was concluded that EMT mediates tumor progression, and reduces OS time in patients with LSCC. E-cadherin/β-catenin co-expression may be associated with clinicopathological parameters. T stage, and the positive co-expression of β-catenin and ZEB2 may be independent predictors of prognosis in LSCC.

A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began in December 2013 in response to hydraulic fracturing. Using a hydraulic fracturing database, we explore relationships between injection parameters and seismicity response. We show that induced earthquakes are associated with completions that used larger injection volumes (10 4 to 10 5 cubic meters) and that seismic productivity scales linearly with injection volume. Injection pressure and rate have an insignificant association with seismic response. Further findings suggest that geological factors play a prominent role in seismic productivity, as evidenced by spatial correlations. Together, volume and geological factors account for ~96% of the variability in the induced earthquake rate near Fox Creek. This result is quantified by a seismogenic index-modified frequency-magnitude distribution, providing a framework to forecast induced seismicity., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background/aims: The adverse effects of obesity on male fertility have been widely reported. In recent years, the relationship between the differential expression of proteins and long non-coding RNAs with male reproductive disease has been reported. However, the exact mechanism in underlying obesity-induced decreased male fertility remains unclear., Methods: We used isobaric tags for relative and absolute quantification to identify differential protein expression patterns in the testis of rats fed a high-fat diet and normal diet. A microarray-based gene expression analysis protocol was used to compare the differences in long non-coding RNAs in high-fat diet-fed and normal diet-fed rats. Five obviously upregulated or downregulated proteins were examined using western blot to verify the accuracy of their expression. Then, we carried out functional enrichment analysis of the differentially expressed proteins using gene ontology and pathway analysis. Finally, the metabolic Gene Ontology terms and pathways involved in the differential metabolites were analyzed using the MetaboAnalyst 2.0 software to explore the co-expression relationship between long non-coding RNAs and proteins., Results: We found 107 proteins and 263 long non-coding RNAs differentially expressed between rats fed a high-fat diet and normal diet. The Gene Ontology term enrichment analysis showed that the protein function most highly enriched was related to negative regulation of reproductive processes. We also found five Gene Ontology terms and two metabolic pathways upregulated or downregulated for both proteins and long non-coding RNAs., Conclusion: The study revealed different expression levels for both proteins and long non-coding RNAs and showed that the function and metabolic pathways of differently expressed proteins were related to reproductive processes. The Gene Ontology terms and metabolic pathways upregulated or downregulated in both proteins and long non-coding RNAs may provide new candidates to explore the mechanisms of obesity-induced male infertility for both protein and epigenetic pathways., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

This study sought to identify sources of the reduced fertility of men with type 2 diabetes mellitus. Significant reductions in semen volume, sperm concentration, and total sperm count were observed in diabetic individuals, while transmission electron microscopy revealed that the structure of mitochondria in the tail of sperm from diabetic patients was damaged. Proteins potentially associated with these sperm defects were identified using proteomics. Isobaric tagging for relative and absolute quantitation labeling and high-performance liquid chromatography-tandem mass spectrometry allowed us to identify 357 proteins significantly differentially expressed in diabetic versus control semen (>1.2 or <0.83). According to gene ontology enrichment and pathway analyses, many of these differentially expressed proteins are associated with sperm function, including binding of sperm to the zona pellucida and proteasome function; of particular interest, half of these proteins were related to mitochondrial metabolism. Protein-interaction networks revealed that a decrease in Cystatin C and Dipeptidyl peptidase 4 in the mitochondria may be sources of the decreased motility of sperm from diabetic patients., (© 2017 Wiley Periodicals, Inc.)

Autosomal recessive woolly hair/hypotrichosis (ARWH/HT: OMIM #278150/604379) is a rare hereditary hair disease characterized by tightly curled hair at birth which can lead to sparse hair later in life. The mutations in both LIPH and LPAR6/P2RY5 are responsible for autosomal recessive woolly hair with or without hypotrichosis (ARWH/HT). To conduct clinical and genetic investigations in four patients from three unrelated Chinese Han families with ARWH/HT, we performed mutation screening of LIPH and LPAR6/P2RY5 gene and identified four mutations in LIPH: c.454G>A, c.614A>G, c.736T>A, c.742C>A. c.736T>A and c.742C>A mutations were reported in previous studies, and c.454G>A, c.614A>G were identified for the first time. We carried out functional studies of the two mutants with c.454G>A (p.Gly152Arg, G152R) or c.614A>G (p.His205Arg, H205R). Interestingly, both of them lead to secretion defects of LIPH, which are involved in the pathogenesis of ARWH/HT., (© The Author(s) 2018. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this work, a solution combustion followed by dissolution in hydrogen peroxide is adopted to achieve a precursor for decorating anatase TiO 2 nanosheets along single-crystalline rutile TiO 2 nanorods, which achieves balsam-pear-like core/shell nanorod arrays with enhanced photoelectrochemical water splitting. The enhanced photoelectrochemical performance is attributed to the novel nanoarchitecture, which can simultaneously offer a high surface area, enhanced light-harvesting, a rutile/anatase junction for charge carrier separation and a conductive pathway for charge carrier collection. The photoanode design can also give hints to other functional materials.

Objective: To evaluate the clinical effects of French door segmented laminectomy decompression for severe cervical OPLL complicated with spinal cord injury., Methods: The clinical data of 38 patients with serious cervical OPLL complicated with spinal cord injury were retrospectively analyzed and these patients were treated with French door segmented laminectomy decompression and internal fixation from June 2012 to June 2014. There were 25 males and 13 females, aged from 42 to 78 years with an average of 58.2 years. Of them, 35 cases suffered from aggravating neurological symptoms with a definite precipitating factor. Spinal cord injury was related to minor injury of the neck, such as hyperextension of the neck in 3 cases. Preoperative Japanese Orthopaedic Score (JOA) was 8.1±1.7 and Neck Disability Index (NDI) was 19.8±4.4. Preoperative CT scans showed the range of OPLL was more than three segments. The spinal canal was occupied 50% to 85% with an average of 70.7%., Results: All the patients were followed up for 10 to 24 months with an average of 15.6 months. The operative time was 90 to 150 min with an average of 120 min and blood loss was 300 to 800 ml with an average of (480±80) ml. At final follow-up, NDI and JOA were 7.5±2.5 and 13.5±2.0, respectively, and they were obviously improved compared with preoperation. Preoperative cervical Cobb angle was (8.10±2.70)° and at final follow-up was (15.60±1.80)°, and there was significant difference between preoperative and postoperative ( P <0.05). Deep infection occurred in 1 case, epidural hematoma in 1 case, C₅ nerve root palsy in 3 cases, and axial symptom in 8 cases after operation. No serious complications, such as vertebral artery injury, cerebrospinal fluid leakage, deterioration of neurological dysfunction, or internal fixation failure was found., Conclusions: French door segmented laminectomy decompression is safe and feasible for severe cervical OPLL complicated with spinal cord injury, and it is worth to be popularized in future., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Type 2 diabetes mellitus (T2DM) is closely related to depression; however, the exact molecular mechnisms of this association are unknown. Here, we investigated whether circular RNAs (circRNAs) in the blood are related to the occurrence of depression in patients with T2DM. Fourteen patients with T2DM and depressive symptoms, as assessed by the Self-Rating Depression Scale, were included in this study. Cutoff points of 44 (total coarse points) and 55 (standard score) were used to define depression. The Patient Health Questionnaire 9 was used for common mental disorders, and a score of 5 or more the cutoff for depression. Microarray assays and quantitative real-time reverse transcription polymerase chain reaction showed that 183 hsa-circRNAs were significantly upregulated, whereas 64 were downregulated in the T2DM with depression group (p < 0.05) compared with that in the T2DM group. Differentially expressed hsa-circRNAs could interact with microRNAs to target mRNA expression. KEGG pathway analysis predicted that upregulation of hsa-circRNA&#95;003251, hsa-circRNA&#95;015115, hsa-circRNA&#95;100918, and hsa&#95;circRNA&#95;001520 may participate in the thyroid hormone, Wnt, ErbB, and mitogen-activated protein kinase signalling pathways. We speculate that differentially expressed hsa-circRNAs could help us to clarify the pathogenesis of depression in patients with T2DM and could represent novel molecular targets for clinical diagnosis and therapy.

Background: Obesity, a common metabolic disease, is a known cause of male infertility due to its associated health risk. Long noncoding RNAs (lncRNAs) have also been reported to be associated with male reproductive diseases; however, their role in the association between high-fat diet-induced obesity (DIO) and male reproduction remains unclear., Methods: We used microarray analysis to compare the expression levels of lncRNAs and mRNAs in the spermatozoa of rats with DIO and normal rats. We selected a few lncRNAs that were obviously up-regulated or down-regulated, and then used RT-PCR to verify the accuracy of their expression. We then performed a functional enrichment analysis of the differentially expressed mRNAs using gene ontology and pathway analysis. Finally, target gene predictive analysis was used to explore the relationship between lncRNAs and mRNAs., Results: The results revealed a statistically significant difference in the fasting blood glucose level in rats with DIO and control rats. We found that 973 lncRNAs and 2,994 mRNAs were differentially expressed in the sperm samples of the DIO rats, compared to the controls. GO enrichment analysis revealed 263 biological process terms, 39 cellular component terms, and 40 molecular function terms ( p  < 0.01) in the differentially expressed mRNAs. The pathway analysis showed that metabolic pathways were most enriched in protein-coding genes., Discussion: To the best of our knowledge, this is the first report to show differences in the expression levels of lncRNAs and mRNAs in the sperms of rats with DIO and normal rats, and to determine the expression profile of lncRNAs in the sperm of rats with DIO. Our results have revealed a number of lncRNAs and pathways associated with obesity-induced infertility, including metabolic pathways. These pathways could be new candidates that help cope with and investigate the mechanisms behind the progression of obesity-induced male infertility., Competing Interests: The authors declare there are no competing interests.

Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups. Exosomes secreted by transfected ADMSCs were instilled into the bladders of postmenopausal rats. The expression of miR-214 and Mfn2 mRNA and EMT markers was assessed by qRT-PCR and western blotting. It was confirmed that Mfn2 was the target gene of miR-214 in IC. Compared with the normal bladder tissues, miR-214 decreased, but Mfn2 increased in IC bladder tissues. Compared with the blank group, the expression of miR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein increased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein decreased in the miR-214 mimics and Mfn2 groups. The expression of MiR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein decreased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein increased in the miR-214 inhibitors group. Our findings indicate that the inhibition of miR-214 promotes the EMT process and contributes to bladder wall fibrosis by up-regulating Mfn2, thus leading to the occurrence of IC in postmenopausal women.

Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.

Aims: To investigate the functional role of serum Human apurinic/apyrimidinic endonuclease 1 (APE1) in prediction of lymph node metastasis in gastric cancer patients. Materials and methods: Serum samples were pre-operational collected from 86 patients with gastric cancer from Tianjin Medical University Cancer Institute and Hospital from March 2016 to August 2016. The serum of APE1 was measured by ELISA development kit and other CA242, CA724, CA199 and CEA levels by electrochemiluminescence assay. Results: The total of 86 patients with gastric cancer was classified into two groups (lymph node positive and negative groups). Using ELISA assay, we found out that the concentration of serum APE1 was higher in lymph node positive group than that of lymph node negative group. The receiver operating characteristic (ROC) curve was performed to analyze, indicating that area under the ROC curve of serum APE1 were better than those of each regular markers (CEA+CA199+CA242+CA724) or combination of these markers. Additionally, the APE1 overexpression was uncovered in tissue of gastric cancer patients with lymph nodes metastases, which is correlation with results of serum APE1. Conclusion: Serum APE1 was identified as a valuable marker for prediction of lymph node metastases in patients with gastric cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

A smart gold nanoparticle based aptasensor is developed for the sensing of this biomarker in a convenient and fast manner. A comprehensive study was performed to elucidate the driving force of DNA adsorption, different factors' effects, such as gold nanoparticle size, DNA length, concentration, and working pH towards spermine sensing by using UV/Vis absorption spectroscopy and isothermal titration calorimetry. It was found that the developed aptasensor could detect spermine by two different sensing mechanisms simply by adjusting the DNA concentration without complicated procedures. Good performance in complicated matrices was proven by the satisfactory results obtained in the spike analysis of both artificial urine and clinical urine samples. Such a flexible and smart approach described here would provide a useful tool for the fast sensing of spermine and prostate cancer screening., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: To investigate the expression of migration-inducing gene 7 (MIG7) in different HCC lines and its relationship with vasculogenic mimicry (VM) formation and metastatic potentiality., Methods: Employing immunostaining to detect MIG7 protein expression and VM formation in 40 matched pairs of primary and metastatic HCC specimens from 40 patients, and investigating the correlation of VM formation with MIG7 protein expression. Detecting VM formation in HCC lines with different metastatic ability (MHCC-97H, MHCC-97L, Huh-7) and human normal hepatocyte line (L-02) through three-dimensional culture, and detecting MIG7 mRNA expression with RT-PCR, investigating the correlation of MIG7 protein expression with VM formation and HCC metastatic potentiality with Western blot assay; screening the HCC cell line with high MIG7 expression., Results: In 40 matched pairs of HCC tissue, there was a significant positive correlation between MIG7 protein expression and VM formation ( r s =0.595, P <0.01). The capability of VM formation of MHCC-97H with high metastatic potentiality was stronger than that of MHCC-97L with low metastatic potentiality and Huh-7 with non-metastatic potentiality, and there was no VM formation in L-02. The result of RT-PCR and Western blot assay indicated the same., Conclusions: MIG7 expression in HCC tissue is high and correlated positively with VM formation. MIG7 expression in different HCC cell lines is coincident with theirs VM formation, invasion and metastasis. MIG7 is a potential target for inhibiting the invasion and metastasis of HCC.

Estrogen affects the generation and transmission of neuropathic pain, but the specific regulatory mechanism is still unclear. Activation of the N-methyl-D-aspartate acid receptor 1 (NMDAR1) plays an important role in the production and maintenance of hyperalgesia and allodynia. The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain. A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats. These rats were then subcutaneously injected with 17β-estradiol, the NMDAR1 antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP-5), or both once daily for 15 days. Compared with injured drug naïve rats, rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency, indicating increased sensitivity to mechanical and thermal pain. Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity (as assessed by immunohistochemistry) and protein (as determined by western blot assay) in spinal dorsal root ganglia. This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5, whereas AP-5 alone did not affect NMDAR1 expression. These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve, and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia., Competing Interests: Conflicts of interest: None declared.

Tissue calcification is a major cause of failure of bioprosthetic heart valves. Aim of this study was to examine whether surface heparin treatment of the decellularized porcine heart valve reduces tissue calcification. Fresh porcine aortic heart valves were dissected as tissue discs and divided into four groups. Group A: controls without treatment, Group B: decellularization only, Group C: decellularization and glutaraldehyde cross-linking, Group D: decellularization and glutaraldehyde cross-linking followed by surface heparin treatment. After implantation in New Zealand White rabbits for 60 days, the explanted heart valve discs from the different study groups underwent a series of histological examinations as well as determination of calcium content by the methyl thyme phenol blue colorimetric method. Results of the explanted heart valve discs for the Von Kossa staining demonstrated that in Group A the heart valve tissue was the most severely stained with black color, whereas in Group D there was hardly any area that was stained black after implantation indicating the least tissue calcification. Furthermore, the inflammatory cells identified by the Hematoxylin-eosin staining appeared to be the least in Group D. The average tissue calcium content was highest in Group A (0.197 ± 0.115 μmol mg -1 ), modest in Group B (0.113 ± 0.041 μmol mg -1 ), and Group C (0.089 ± 0.049 μmol mg -1 ), and the lowest in Group D (0.019 ± 0.019 μmol mg -1 , p < 0.05). These results suggest that surface heparin treatment tends to reduce tissue calcification of the dellellularized porcine heart valve in a rabbit intramuscular implantation model. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 400-405, 2017., (© 2015 Wiley Periodicals, Inc.)

The present study was conducted to evaluate the radiological findings, particularly the ultrasonographic (US) characteristics of sclerosing adenosis (SA), and their correlation with histopathological results. A retrospective review identified 191 patients with a total of 200 lesions histopathologically confirmed as SA following breast surgery between July 2009 and December 2012. Of the 191 patients, 145 (151 lesions) with SA as the major component were included for US and mammographic (MG) analysis. All 145 patients analyzed were female, with a mean age ± standard deviation of 46.8±7.8 years (range, 25-71 years). All 145 patients underwent US examination and the imaging findings included heterogeneously echogenic areas in 9.3% (14/151), masses in 51.7% (78/151), masses with calcifications in 13.9% (21/151), focal acoustic shadowing in 4.0% (6/151) and were negative in 21.2% (32/151) patients. Among the 119 lesions with visible abnormalities, 87.4% (104/119) were hypoechoic, 58.0% (69/119) were irregular in shape, 52.1% (62/119) had an ill-defined margin, calcifications were found in 17.6% (21/119) and 7.6% (9/119) were hypervascular, while none of the characteristics mentioned above were significantly correlated with histopathology. A total of 136 patients underwent MG at the Fudan University Shanghai Cancer Center, and the imaging findings included microcalcifications in 31.6% (43/136), masses in 23.5% (32/136), asymmetric focal density in 14.7% (20/136), focal architectural distortion in 22.8% (31/136), and were negative in 7.4% (10/136). The mass lesions were fewer on MG compared with US (23.5 vs. 65.6%, respectively). The area under the curve of US distinguishing between benign and malignant lesions was significantly larger compared with that of MG (0.547 vs. 0.497, respectively; P=0.036). In the 60 lesions that were overestimated by Breast Imaging Reporting and Data System US category, one or more characteristics of malignancy were found on US imaging. The most common finding of SA was masses with or without calcifications on US and microcalcifications on MG. The accuracy of US was limited, but higher compared with that of MG; however, SA mimicking the characteristics of malignancy may contribute to misdiagnosis with US.

Purpose: To compare the diagnostic efficiency of digital breast tomosynthesis (DBT) plus digital mammography (DM) and magnetic resonance imaging (MRI) plus DM in symptomatic women., Materials and Methods: The protocol used in our study was accepted by the ethics committee at our hospital, and informed consent was obtained from all patients. Between June and December 2014, 197 patients with 238 histologically proven lesions all underwent DM, DBT and MRI. Two radiologists were responsible for interpreting all images according to the Breast Imaging Reporting and Data System (BI-RADS). The diagnostic performance of each method was assessed by receiver-operating characteristic (ROC) curve. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were compared using McNemar's test and Fisher's exact test. A Kappa test was used to assess the interobserver agreement., Results: The area under the ROC curve (AUC) was lower in the group that underwent DM alone (Radiologist1 [R1], 0.849; Radiologist2 [R2], 0.850) than in the group that underwent DBT plus DM (R1, 0.907, P = 0.0204; R2, 0.900, P = 0.0239) and MRI plus DM (R1, 0.939, P = 0.0006; R2, 0.935, P = 0.0009). However, the difference between the group that received DBT plus DM and the group that received MRI plus DM was not significant (R1, P = 0.1262; R2, P = 0.0843). The accuracy (R1, 71.8%; R2, 71.4%) and sensitivity (R1, 71.9%; R2, 71.2%) of DM were lower than those of DBT ((accuracy: R1, 85.3%, P = 0.001; R2, 83.6%, P < 0.001; sensitivity: R1,92.1%, P < 0.001; R2, 90.8%, P < 0.001) and MRI combined with DM (accuracy: R1, 90.3%, P = 0.001; R2, 90.7%, P < 0.001; sensitivity: R1, 94.7%, P < 0.001; R2, 95.4%, P < 0.001). In contrast, no significant difference was observed between DBT and MRI combined with DM (accuracy: R1, P = 0.644; R2, P = 0.360; sensitivity: R1, P = 0.502; R2, P = 0.359). The interobserver agreement of each method was excellent (k = 0.894 0.919 and 0.882 for DM, DBT and MRI combined with DM, respectively)., Conclusion: The diagnostic performance of DBT and MRI combined with DM is superior to that of DM alone in symptomatic women; MRI plus DM is slightly better than that of DBT plus DM, but this difference was not statistically significant.

Purpose: To analyze and compare the difference of condylar position between Angle Class I and Class II malocclusion patients using cone-beam CT (CBCT)., Methods: Thirty Class I patients, 30 Class II division 1 patients and 30 Class II division 2 patients were selected in this study. Each patient underwent CBCT. The images in the oblique position perpendicular to the condyloid process were reconstructed by Examvision software. The joint space was measured by Exam Vision software. The data were processed with SPSS17.0 software package., Results: The upper joint space was larger in Class II, the posterior joint space was smaller in Class II patients; and in Class II division 1 patients, both of the upper and anterior joint spaces were larger than in Class II division 2 patients，the differences were significant (P<0.05). The length of condyle was longer in Class I patients than in Class II patients., Conclusions: The condylar position in Class II division 2 patients was lower and further backward. The length of condyle is shortest in Class II division 2 patients.

Objective: To investigate the inhibitory effect of migration-inducing gene-7(Mig-7)interfered with retrovirus-mediated RNA(shRNA)combined with recombinant human endostatin(ES)on the growth and metastasis of subcutaneous xenograft of human hepatoma cells in nude mice. Methods: Two Mig-7-mRNA oligonucleotide sequences(Mig-7-shRNA-1 and Mig-7-shRNA-2)and one sequence as a negative control(Mig-7-shRNA-N)were designed. The specific Mig-7-shRNA recombinant retrovirus expression vector plasmid was constructed and used for the transfection of human hepatoma MHCC-97H cells with high expression of Mig-7. The subcutaneous xenograft tumor model of human hepatocellular carcinoma(HCC)in nude mice was established, and according to the condition of transfection and administration, the nude mice were divided into pSIREN-M1 group, pSIREN-MN group, ES group, and pSIREN-M1+ES group. The xenograft tumor volume, mass, and metastasis were compared between groups. Immunohistochemistry was used to observe the formation of vasculogenic mimicry(VM)in xenograft tumor and the difference in tumor microvascular density(MVD), and Western blot was used to measure the expression of Mig-7 and vascular endothelial growth factor(VEGF)in each group. A one-way analysis of variance was used for comparison between groups, and the Fisher's exact test was used for comparison of continuous data between groups. Results: Compared with the pSIREN-MN group, the pSIREN-M1 group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, and formation of VM( P < 0.05), as well as significantly higher VEGF expression and MVD( P < 0.05). Compared with the pSIREN-MN group, the ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, VEGF expression, and MVD( P < 0.05), as well as significantly higher Mig-7 expression and formation of VM( P < 0.05). Compared with the pSIREN-M1 group and the ES group, the pSIREN-M1+ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, formation of VM, VEGF expression, and MVD( P < 0.05). Conclusion: Mig-7-shRNA recombinant retrovirus combined with ES has a better inhibitory effect on the growth and metastasis of HCC xenograft tumor than Mig-7-shRNA recombinant retrovirus or ES alone. The anti-tumor angiogenesis therapy alone, which targets vascular endothelial cells in vivo, has a limited effect, since it may promote the formation of VM.

Protein tyrosine kinases belonging to the Janus kinase (JAK) family are associated with many cytokine receptors, which, on ligand binding, regulate important cellular functions such as proliferation, apoptosis and differentiation. The protective effects of JAK inhibitors on fibrotic diseases such as myelofibrosis and bone marrow fibrosis have been demonstrated in previous studies. The JAK inhibitor SHR0302 is a synthetic molecule that potently inhibits all members of the JAK family, particularly JAK1. However, its effect on hepatic fibrosis has not been investigated to date, to the best of our knowledge. In the present study, the effects of SHR0302 on the activation, proliferation, migration and apoptosis of hepatic stellate cells (HSCs) as well as HSC collagen production were investigated. Our data demonstrated that treatment with SHR0302 (10-9-10-5 mol/l) exerted an inhibitory effect on the activation, proliferation and migration of HSCs. In addition, the expression of collagen I and collagen III were significantly decreased following treatment with SHR0302. Furthermore, SHR0302 induced the apoptosis of HSCs, which was demonstrated by Annexin V/PI staining. SHR0302 significantly increased the activation of caspase-3 and Bax in HSCs whereas it decreased the expression of Bcl-2. SHR0302 also inhibited the activation of Akt signaling pathway. The pharmacological inhibition of the JAK1/signal transducer and activator of transcription (STAT)3 pathway led to the disruption of functions essential for HSC growth. Taken together, these findings provide evidence that SHR0302 may have the potential to alleviate hepatic fibrosis by targeting HSC functions.

Background: Combined hepatocellular and cholangiocarcinoma (CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); however, its cellular origin remains unclear. The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC., Methods: The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC (SHC). Loss of heterozygosity (LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC. Expression of hepatocyte markers [hepatocyte paraffin 1 (Hep Par 1) and glypican 3 (GPC3)] and cholangiocyte markers [cytokeratin (CK)7 and 19] in tumor tissues was examined by immuno histochemical analysis., Results: In the 16 CHC specimens, the difference in LOH patterns between HCC and ICC was less than 30%, suggesting the same clonal origin of HCC and ICC. Consistent with this finding, immunohistochemical analysis revealed that hepatocyte markers (Hep Par 1 and GPC3) and cholangiocyte markers (CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9% of CHC specimens, suggesting that the two components shared a similar phenotype with hepatic progenitor cells (HPCs). On the contrary, in all 10 SHC cases, the difference in LOH patterns between the HCC and ICC components was greater than 30%, suggesting different clonal origins of HCC and ICC. Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC (P < 0.05)., Conclusions: Our results suggest that the HCC and ICC components of CHC may originate from the same clone, having the potential for dual-directional differentiation similar to HPCs. CHC tended to exhibit the biological behaviors of both HCC and ICC, which may enhance the infiltrative capacity of tumor cells, leading to poor clinical outcomes for patients with CHC.

Aim: Nowadays, cathepsins have been reported to be related to aging. The aim of this study is to evaluate the association between serum levels of cathepsin D (CTSD) and human aging., Methods: In the present study, we analyzed the serum levels of CTSD and its relation with levels of sirtuin1 (SIRT1) and endothelial nitric oxide synthase (eNOS) activity, which were known having an important role in aging. This study recruited 90 healthy subjects (62 men and 28 women), which were subdivided into three groups with respect to age: young (about 19 years old, n = 30), middle-age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of CTSD and SIRT1 were measured by enzyme-linked immunosorbent assay, and eNOS activity was assessed by the conversion of 14(C)-L-arginine to 14(C)-L-citrulline., Results: Elderly subjects had significantly lower CTSD, SIRT1, and eNOS than younger ones. Serum levels of CTSD were negatively correlated with age. There was a statistically significant positive correlation between serum levels of CTSD, eNOS, and SIRT1., Conclusions: This study shows lower serum CTSD values in elderly subjects than in younger subjects. This is the first to demonstrate age-related changes in cathepsin D levels in humans and the association between SIRT1 and eNOS.

Objective: To analyze the mammographic, MRI, and clinicopathological characteristics of primary breast lymphoma (PBL)., Methods: Clinicopathological characteristics were retrospectively reviewed and analyzed in 32 patients with histopathologically proven PBL. All cases were female (mean age, 50 years; median age 46 years; range, 30-68 years)., Results: In the 32 cases, there were bilateral tumors in 5 cases and 27 cases of unilateral involvement. The patients presented with a painless mass in 25 cases and with pain in 7 cases. Rapid enlargement was observed in 6 cases. Mammograms of 17 tumors showed a round, circumscribed mass with high density or iso-density in 9, asymmetry in 7 and no abnormality was found in one. 37 lesions were detected on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in 29 patients, among which 25 (67.6%) lesions appeared as enhancing masses and 12 (32.4%) lesions as non-mass enhancements. All lesions showed iso- or hypo-intense signal on the T1WI and hyper-intense signal on the T2W1. Analysis of the enhancing masses based on the 2013 ACR BI-RADS lexicon revealed that among the mass descriptors in 25 lesions, the most common features were circumscribed or irregular margin in 24 (96.0%) and homogeneous internal pattern in 19 (76.0%). Of the 12 non-mass enhancing lesions, the most common descriptors included regional or multiple regional distribution in 6 (50.0%), and heterogeneous internal pattern in 8 (66.7%). The tumors showed early enhancement with penetrating vessels on DCE-MRI in 16 lesions, associated with skin thickening in 14, and axillary lymphadenopathy in 19. The time-signal intensity curve (TIC) in 14 patients was mainly of type Ⅲ (7/14, 50.0%)., Conclusions: Some imaging features may alert the diagnosis of primary breast lymphoma, but final diagnosis depends on histopathology. Early diagnosis is helpful for selecting appropriate treatment regimens.

Celastrol, a natural compound derived from the Chinese herb Tripterygium wilfordii Hook F, has been proven to inhibit heat shock protein 90 (HSP90) activity and has attracted much attention because of its promising effects in cancer treatment and in ameliorating degenerative neuron diseases. However, the HSP90 structure involved in celastrol interaction is not known. Here, we report a novel celastrol-binding pocket in the HSP90 dimer, predicted by molecular docking. Mutation of the two key binding pocket amino acids (Lys546 and Tyr493) disrupted the binding of celastrol to HSP90 dimers, as detected by isothermal titration calorimetry (ITC). Interestingly, such mutations also reduced binding between HSP90 and the cochaperone Cdc37, thus providing a new explanation for reported findings that celastrol shows more obvious effects in disrupting binding between HSP90 and Cdc37 than between HSP90 and other cochaperones. In short, our work discloses a novel binding pocket in HSP90 dimer for celastrol and provides an explanation as to why celastrol has a strong effect on HSP90 and Cdc37 binding.

Aims: Previous studies have suggested that high mobility group box-1 protein (HMGB1) binds to the toll-like receptor 4 (TLR4) signaling mediates the progression of various inflammatory diseases. But the roles of HMGB1 and TLR4 in aging remain poorly unknown. In this study, we aimed to investigate the serum levels of HMGB1 and myeloid differentiation factor 88 (MyD88), which is one of TLR4's intracellular adaptor proteins during human aging process and their relevance with cathepsin B (CTSB)., Methods: This research was conducted using the blood samples provided by healthy people (n = 90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 25 years old, n = 30), middle age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of HMGB1, MyD88 and CTSB were measured using an enzyme-linked immunosorbent assay., Results: The serum levels of HMGB1 and MyD88 were significantly decreased in the aged group compared with those in the young group. Linear regression analysis showed that HMGB1 and MyD88 positively correlated with CTSB among the whole healthy people. A negative correlation was determined between MyD88 and age., Conclusions: The serum levels of HMGB1 and MyD88 significantly decreased with age. MyD88, but not HMGB1, was negatively correlated with age.

The transforming growth factor β (TGF-β) superfamily of cytokines is multifunctional and involved in the regulation of cell growth and differentiation. TGF-β can induce an epithelial-mesenchymal transition (EMT) of both epithelial and endothelial cells. This has consequences for cancer progression in regards to both migration and invasion abilities. The type III TGF-β receptor (TβRIII) is a ubiquitously expressed TGF-β co-receptor which regulates TGF-β signaling and the progression of various types of cancer. Previous studies have shown that TβRIII exhibits abnormal expression and plays an essential role in regulating cancer invasion and metastasis, while little is known in regards to its role in hepatocellular carcinoma (HCC) progression. In the present study, we designed the present research to study the role of TβRIII in the invasion and metastasis of HCC and the possible mechanisms involved. The results demonstrated decreased expression of TβRIII in HCC patient tissues and human HCC cell lines. TGF-β1 stimulation led to the increased migratory ability and reduced expression of TβRIII in HCC cells. In addition, knockdown of TβRIII by small interfering RNA (siRNA) promoted the migration and invasion of HCC cells and induced activation of the Smad2 and Akt pathways. All the results suggest that TβRIII is a novel suppressor of HCC progression.