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Most hydrogels become frozen at subzero temperatures, leading to degraded properties and limited applications. Cryoprotectants are massively employed to improve anti-freezing property of hydrogels; however, there are accompanied disadvantages, such as varied networks, reduced mechanical properties, and the risk of cryoprotectant leakage in aqueous conditions. Reported here is the glassy hydrogel having intrinsic anti-freezing capacity and excellent optical and mechanical properties at ultra-low temperatures. Supramolecular hydrogel of poly(acrylamide-co-methacrylic acid) with moderate water content (≈50 wt.%) and dense hydrogen-bond associations is in a glassy state at room temperature. Since hydrogen bonds become strengthened as the temperature decreases, this gel becomes stronger and stiffer, yet still ductile, with Young's modulus of 900 MPa, tensile strength of 30 MPa, and breaking strain of 35% at -45 °C. This gel retains high transparency even in liquid nitrogen. It also exhibits unique phosphorescence due to presence of carbonyl clusters, which is further enhanced at subzero temperatures. Further investigations elucidate that the intrinsic anti-freezing property is related to a fact that most water molecules are tightly bound and confined in the glassy matrix and become non-freezable. This correlation, as validated in several systems, provides a roadmap to develop intrinsic anti-freezing hydrogels for widespread applications at extreme conditions., (© 2023 Wiley-VCH GmbH.)

Joints, as a flexing element to connect different parts, are widespread in natural systems. Various joints exist in the body and play crucial roles to execute gestures and gaits. These scenarios have inspired the design of mechanical joints with passive, hard materials, which usually need an external power supply to drive the transformations. The incorporation of soft and active joints provides a modular strategy to devise soft actuators and robots. However, transformations of responsive joints under external stimuli are usually in uni-mode with a pre-determined direction. Here, hydrogel joints capable of folding and twisting transformation in bi-mode are reported, which enable the composite hydrogel to form multiple configurations under constant conditions. These joints have an in-plane gradient structure and comprise stiff, passive gel as the frame and soft, active gel as the actuating unit. Under external stimuli, the response mismatch between different gels leads to out-of-plane folding or twisting deformation with the feature of bistability. These joints can be modularly integrated with other gels to afford complex deformations and multistable configurations. This approach favors selective control of hydrogel's architectures and versatile design of hydrogel devices, as demonstrated by proof-of-concept examples. It shall also merit the development of metamaterials, soft actuators, and robots, etc., (© 2023 Wiley-VCH GmbH.)

Viscoelasticity is a generic characteristic of soft biotissues and polymeric materials, endowing them with unique time- and rate-dependent properties. Here, by spatiotemporally tailoring the viscoelasticity in tough supramolecular hydrogels, we demonstrate reprogrammable morphing of the gels based on differential viscoelastic recovery processes that lead to internal strain mismatch. The spatial heterogeneity of viscoelasticity is encoded through integrating dissimilar hydrogels or by site-specific treatment of a singular hydrogel. The temporal morphing behavior of tough gels, including a fast deformation process and then a slow shape-recovery process, is related to the kinetics of associative interactions and the entropic elasticity of supramolecular networks after pre-stretching and release, which takes place spontaneously in the absence of external stimuli. Such a kinetically driven morphing mechanism resolves the trade-off between the mechanical robustness and shape-changing speed in tough hydrogels with dense entanglements and physical associations, and should be applicable to other viscoelastic materials. A numerical theory for the temporal morphing of tough supramolecular gels has been formulated by dynamic coupling of viscoelastic recovery and mechanics of deformations, which is further implemented to predict the sophisticated morphed structures. Furthermore, magnetic particles are incorporated into the morphed tough hydrogels to devise versatile soft actuators and robots for specific applications.

The design of soft robots capable of navigation underwater has received tremendous research interest due to the robots' versatile applications in marine explorations. Inspired by marine animals such as jellyfish, scientists have developed various soft robotic fishes by using elastomers as the major material. However, elastomers have a hydrophobic network without embedded water, which is different from the gel-state body of the prototypes and results in high contrast to the surrounding environment and thus poor acoustic stealth. Here, we demonstrate a manta ray-inspired soft robot fish with tailored swimming motions by using tough and stiff hydrogels as the structural elements, as well as a dielectric elastomer as the actuating unit. The switching between actuated and relaxed states of this unit under wired power leads to the flapping of the pectoral fins and swimming of the gel fish. This robot fish has good stability and swims with a fast speed (∼10 cm/s) in freshwater and seawater over a wide temperature range (4-50 °C). The high water content (i.e., ∼70 wt %) of the robot fish affords good optical and acoustic stealth properties under water. The excellent mechanical properties of the gels also enable easy integration of other functional units/systems with the robot fish. As proof-of-concept examples, a temperature sensing system and a soft gripper are assembled, allowing the robot fish to monitor the local temperature, raise warning signals by lighting, and grab and transport an object on demand. Such a robot fish should find applications in environmental detection and execution tasks under water. This work should also be informative for the design of other soft actuators and robots with tough hydrogels as the building blocks.

Processing tough hydrogels into sophisticated architectures is crucial for their applications as structural elements. However, Digital Light Processing (DLP) printing of tough hydrogels is challenging because of the low-speed gelation and toughening process. Described here is a simple yet versatile system suitable for DLP printing to form tough hydrogel architectures. The aqueous precursor consists of commercial photoinitiator, acrylic acid, and zirconium ion (Zr 4+ ), readily forming tough metallo-supramolecular hydrogel under digital light because of in situ formation of carboxyl-Zr 4+ coordination complexes. The high-stiffness and antiswelling properties of as-printed gel enable high-efficiency printing to form high-fidelity constructs. Furthermore, swelling-induced morphing of the gel is also achieved by encoding structure gradients during the printing with grayscale digital light. Mechanical properties of the printed hydrogels are further improved after incubation in water due to the variation of local pH and rearrangement of coordination complex. The swelling-enhanced stiffness affords the printed hydrogel with shape fixation ability after manual deformations, and thereby provides an additional avenue to form more complex configurations. These printed hydrogels are used to devise an impact-absorption element or a high-sensitivity pressure sensor as proof-of-concept examples. This work should merit engineering of other tough gels and extend their scope of applications in diverse fields., (© 2022 Wiley-VCH GmbH.)

Recent years have witnessed the rapid development of sustainable materials. Along this line, developing biodegradable or recyclable soft electronics is challenging yet important due to their versatile applications in biomedical devices, soft robots, and wearables. Although some degradable bulk hydrogels are directly used as the soft electronics, the sensing performances are usually limited due to the absence of distributed conducting circuits. Here, sustainable hydrogel-based soft electronics (HSE) are reported that integrate sensing elements and patterned liquid metal (LM) in the gelatin-alginate hybrid hydrogel. The biopolymer hydrogel is transparent, robust, resilient, and recyclable. The HSE is multifunctional; it can sense strain, temperature, heart rate (electrocardiogram), and pH. The strain sensing is sufficiently sensitive to detect a human pulse. In addition, the device serves as a model system for iontophoretic drug delivery by using patterned LM as the soft conductor and electrode. Noncontact detection of nearby objects is also achieved based on electrostatic-field-induced voltage. The LM and biopolymer hydrogel are healable, recyclable, and degradable, favoring sustainable applications and reconstruction of the device with new functions. Such HSE with multiple functions and favorable attributes should open opportunities in next-generation electronic skins and hydrogel machines., (© 2022 Wiley-VCH GmbH.)

Venus flytrap and bladderwort, capable of rapid predation through a snapping transition, have inspired various designs of soft actuators and robots with fast actions. These designs, in contrast to their natural counterparts, often require a direct force or pressurization. Here, we report a bistable domal hydrogel structure capable of spontaneous and reversible snapping under an electric field. Unlike a mechanical force, the electric field does not drive the gel directly. Instead, it redistributes mobile ions that direct the migration of water molecules and bends the polyelectrolyte hydrogel. Subject to constraint from surrounding neutral gel, the elastic energy accumulates until suddenly released by snapping, just like the process in natural organisms. Several proof-of-concept examples, including an optical switch, a speedy catcher, and a pulse pump, are designed to demonstrate the versatile functionalities of this unit capable of articulate motion. This work should bring opportunities to devise soft robotics, biomedical devices, etc.

Fluorescent hydrogels have attracted tremendous attention recently in the field of information security due to the booming development of information technology. Along this line, it is highly desired to improve the security level of concealed information by the advancements of materials and encryption technologies. Here we report multi-level encryption of information in a bilayer hydrogel with shape-morphing ability and patterned fluorescence. This hydrogel is composed of a fluorescence layer containing chromophore units in the poly(acrylic acid) network and an active layer with UV-absorption agents in the poly( N -isopropylacrylamide- co -acrylic acid) network. The former layer exhibits tunable fluorescence tailored by UV light irradiation to induce unimer-to-dimer transformation of the chromophores, facilitating the write-in of information through photolithography. The latter layer is responsive to temperature, enabling morphing of the bilayer hydrogel. Therefore, the bilayer hydrogel encoded with patterned fluorescent patterns can deform into three-dimensional configurations at room temperature to conceal the information, which is readable only after successive procedures of shape recovery at an appropriate temperature and under UV light irradiation from the right direction. The combination of morphing materials and patterned fluorescence as a new avenue to improve the encryption level of information should merit the design of other smart materials with integrated functions for specific applications.

Constructed via in-plane heterojunction contacts between the semiconducting 2H phase (as the channel) and the metallic 1T' phase (as the electrode), two-dimensional (2D) transition metal dichalcogenide (TMD) field-effect transistors (FETs) have received much recent attention because they significantly reduce contact resistance. In this paper, ab initio quantum transport simulation is done to study and predict the electronic states and contact properties of the 2H-MoS 2 /1T'-MX 2 (WS 2 , TaSe 2 , NbSe 2 , MoSe 2 , TaS 2 , and NbS 2 ) in-plane heterojunctions. It is found that the interfacial states are not obvious and the fluctuation of the average electron density at the 1T'/2H phase boundary is small for all 2H-MoS 2 /1T'-MX 2 heterojunctions. The average electrostatic potential differences (Δ V ) are all negative, which is beneficial to promote the charge transfer from 1T'-MX 2 to 2H-MoS 2 . Moreover, the p-type Schottky contact of the 2H-MoS 2 /1T'-MX 2 heterojunctions is formed and the Φ SB,P values are 0.609 eV, 0.625 eV, 0.641 eV, 0.617 eV, 0.469 eV and 0.477 eV for 1T'-WS 2 , 1T'-TaSe 2 , 1T'-NbSe 2 , 1T'-MoSe 2 , 1T'-TaS 2 , and 1T'-NbS 2 , respectively. The results provide theoretical guidance for designing two-dimensional material devices.

Objective: This study examined the association between iron status and a set of breast cancer risk factors among U.S. adult women aged 20-80 years., Methods: Data from National Health and Nutrition Examination Survey (2017-2018) were used to examine the relation between serum ferritin, serum iron and transferrin saturation with a set of breast cancer risk factors [body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), fasting plasma glucose, insulin and HOMA-IR]. The multivariable linear regressions were used controlling for age, race/ethnicity, menopause status, education level, smoking status, alcohol consumption, physical activity, high-sensitivity C-reactive protein (hsCRP) and total energy intake., Results: HbA1c, BMI and waist circumference data were available for 1902 women with a fasting sample (n = 913) for fasting plasma glucose, insulin and HOMA-IR. Transferrin saturation had significant, inverse associations with BMI, waist circumference and HbA1c. The size of difference observed were that participants in the fourth quartile of transferrin saturation had a 4.50 kg/m 2 smaller BMI, a 9.36 cm smaller waist circumference and a 0.1 % lower HbA1c level than participants in the first quartile. Similarly, serum iron concentrations were inversely associated with BMI and waist circumference. In addition, serum iron had significant, inverse associations with insulin and HOMA-IR. Sensitivity analyses among men gave similar results. For serum ferritin, there was a trend towards a positive association between waist circumference, HbA1c and fasting plasma glucose with serum ferritin. However, the associations did not reach statistical significance among women., Conclusions: Iron status may impact breast cancer risk via effects on adiposity or glucose metabolism. The findings should be confirmed with further prospective data., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

A simple and effective approach is demonstrated to fabricate tough metallosupramolecular hydrogel films of poly(acrylic acid) by one-pot photopolymerization of the precursor solution in the presence of Zr 4+ ions that form coordination complexes with the carboxyl groups and serve as the physical crosslinks of the matrix. Both as-prepared and equilibrated hydrogel films are transparent, tough, and stable over a wide range of temperature, ionic strength, and pH. The thickness of the films can be easily tailored with minimum value of ≈7 μm. Owing to the fast polymerization and gelation process, kirigami structures can be facilely encoded to the gel films by photolithographic polymerization, affording versatile functions such as additional stretchability and better compliance of the planar films to encapsulate objects with sophisticated geometries that are important for the design of soft electronics. By stencil printing of liquid metal on the hydrogel film with a kirigami structure, the integrated soft electronics shows good compliance to cover curved surfaces and high sensitivity to monitor human motions. Furthermore, this strategy is applied to diverse natural and synthetic macromolecules containing carboxyl groups to develop tough hydrogel films, which will open opportunities for the applications of hydrogel films in biomedical and engineering fields., (© 2021 Wiley-VCH GmbH.)

Background: To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer using real-world clinical data., Methods: Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were retrospectively analyzed. Curative effect and adverse reactions were evaluated., Results: A total of 110 patients were enrolled in this study, and 87.3% received salvage chemotherapy. The median number of salvage treatment lines was 5 (range: 1-19). The median follow-up duration was 12 months (range: 1-56.3 months), the overall response rate (ORR) was 6.4%, the clinical benefit rate (CBR) was 31.8%, the median progression-free survival (mPFS) was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival (OS) was 17 months (95% CI: 12.1-21.9 months). The mPFS for patients who received ≤2 treatment line was 11.8 months (95% CI: 4.3-19.3 months). Univariate and multivariate analyses suggested that absence of liver metastases, secondary endocrine resistance, and number of metastasis sites <3 were the main factors influencing the benefit of everolimus combined with endocrine therapy. The most common adverse events of grade 3 were: stomatitis (5.5%), non-infectious pneumonia (1.8%), and erythra (1.8%). No grade 4 adverse reactions were observed., Conclusions: Our results showed that everolimus (5 mg/day) combined with endocrine therapy was effective and relatively safe for patients with hormone receptor-positive, HER2-negative metastatic breast cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4273). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Triple negative breast cancer (TNBC) is a special type of breast cancer. At present, the major treatment for TNBC is chemotherapy. Neoadjuvant therapy and obtained pathology completed response could bring the TNBC patients better prognosis. The most used TNBC chemotherapy protocols are established on the basis of anthracycline and taxane. Through the thorough knowledge of molecular mechanism of TNBC, neoadjuvant therapy protocols have optimized, including the use of platinum, immune checkpoint inhibitors and poly-ADP-ribose polymerase inhibitors, and assumed positive outcome for TNBC patients.

Objective: To explore the value of speculating etiology of the magnetic resonance imaging (MRI) T1 weighted imaging (T1WI) labyrinthine high signal ratio in patients with unilateral sudden deafness accompanied by vertigo and tinnitus and its relationship with hearing prognosis. Methods: Fifty-two patients with unilateral sudden deafness accompanied by vertigo and tinnitus who were admitted to Beijing Tongren Hospital Affiliated to Capital Medical University from January 2016 to July 2019 were collected, including 27 males and 25 females, aged (47.7±15.1) years. The inner ear MRI data of 52 patients (17 plain scan, 35 enhanced scan) with unilateral sudden deafness were retrospectively analyzed. Two radiologists independently measured the labyrinthine high signal intensity of the affected side and the contralateral normal side on T1WI and enhanced T1WI and calculated the signal ratio (the normal labyrinth signal was subtracted from the affected signal and then divided by the normal signal). The etiology of the enhanced group was judged based on two methods, including whether the abnormal high signal was enhanced or not (unenhancement indicated hemorrhage and enhancement indicated inflammation), and the locations of labyrinthine involvement on enhanced three-dimensional fluid attenuated inversion recovery (3D-FLAIR) (inflammation usually involved the perilymph spaces, while hemorrhage involved the perilymph and endolymph spaces). In the plain group, the locations of labyrinthine involvement on 3D-FLAIR was applied to infer the potential etiology. Results: The two methods presumed that 8 cases might be hemorrhage (22.9%, 8/35) and 27 be inflammation (77.1%, 27/35) in the enhanced group, which had a high consistency, while it was speculated that 7 patients might be hemorrhage (7/17) and 10 patients be inflammation (10/17) in the plain group. The measurement results of the two radiologists were highly consistent within and between the groups [the intraclass correlation coefficient (ICC) values were greater than 0.800]. The area under the receiver operating characteristic (ROC) curve (AUC) of the T1WI high signal ratio in the enhanced group for speculating etiology was 0.949 ( P <0.01), when the predictive threshold value was 0.467, with a sensitivity of 96.3% and a specificity of 87.5%. It might be hemorrhage when the ratio was higher than the threshold value, otherwise it was inflammation. The T1WI labyrinthine high signal ratio was higher in the hemorrhage group than that of the inflammation group, and the hearing prognosis was worse (all P <0.05). The T1WI labyrinthine high signal ratio of the unrecovered group was higher than that of the recovered group ( P =0.034). Conclusions: The etiology of labyrinthine high signal formation can be inferred by quantitative values combined with the involved sites. The high signal in the labyrinth indicates poor hearing prognosis, the higher the signal intensity, the greater the possibility of hemorrhage and the worse the hearing prognosis.

Morphing materials have promising applications in soft robots, intelligent devices, and so forth. Among the various design strategies, kirigami structures are recognized as a powerful tool to obtain sophisticated 3D configurations and unprecedented properties from planar designs on common materials. Here, some kirigami designs are demonstrated for programmable, multistable 3D configurations from composite hydrogel sheets. Via photolithographic polymerization, perforated composite hydrogel sheets are fabricated, in which soft and active hydrogel strips are patterned in stiff and passive hydrogel frames. When immersed in water, the gel strips buckle out of plane due to swelling mismatch. In the kirigami structures, the geometric continuity is disrupted by the introduction of cutouts, and thus the degrees of deformation freedom increases remarkably. Multiple configurations are obtained in a single composite hydrogel by controlling the buckling direction of each strip. Multitier configurations are also obtained by using a hierarchically designed kirigami structure. A multicontact switch of an electric circuit is designed by harnessing the multitier gel configurations. Furthermore, a rotation mode is realized by introducing chirality in the kirigami design. The versatile design of the kirigami structure for programmable deformations should be applicable for other intelligent materials toward promising applications in biomedical devices and flexible electronics., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The geometric error motions of rotary stages greatly affect the accuracy of constructed machines such as machine tools, measuring instruments, and robots. In this paper, an embedded sensor system for real-time measurement of two radial and three angular error motions of a rotary stage is proposed, which makes use of a rotary encoder with multiple scanning heads to measure the rotational angle and two radial error motions and a miniature autocollimator to measure two tilt angular errors of the axis of rotation. The assembly errors of the grid disc of the encoder and the mirror for autocollimator are also evaluated and compensated. The developed measuring device can be fixed inside the rotary stage. In the experiments, radial error motions of two points on the axis ( h = 5 mm and 60 mm) were measured and calibrated with LVDTs, and the data showed that the radial error motions of the axis were less than 20 μm, and the calibration residual errors were less than 2 μm. When intermittent external forces were applied to the stage, the change of the stage's error motion could also be monitored accurately.

Objective: To investigate the visualization of endolymph in patients with otogenic vertigo by intravenous administration of single dose of gadolinium contrast agents and magnetic resonance three-dimensional fluid-attenuated inversion recovery sequence (3D-FLAIR MRI), and further assess the extent of endolymphatic hydrops. Methods: From Beijing Tongren Hospital of Capital Medical University between October 2017 and June 2018, 30 patients (16 males, 14 females) with unilateral otogenic vertigo were involved in this study, with the age of 30 to 68 years, mean age of (53±10) years. Eight hours after intravenous administration of single dose (0.1 mmol/kg, body weight) of gadopentetate (Gd-DTPA), 3D-FLAIR sequence was performed in 30 patients. The location of endolymphatic hydrops was observed and then the degree of hydrops was quantitatively elevated by two radiologists. The consistency test was used to analyze the location and degree of endolymphatic hydrops in the two radiologists and the paired t -test was used to compare the difference between the affected and healthy side of endolymphatic spaces of the patients with otogenic vertigo. Results: In 30 patients, the gadolinium distributed in all parts of the perilymph inside the inner ear, and can accurately outline the boundaries of the peri-and endolymph. Twenty-six patients (26/30, 86.7%) were found to have unilateral endolymphatic hydrops, including 18 mild hydrops, 8 significant hydrops. The two radiologists had a very good agreement on the assessment of endolymphatic hydrops( kappa =0.864, ICC=0.959). In the 3D-FLAIR MR images of 26 patients with endolymphatic hydrops, the saccule (26/26, 100%) had a higher rate of hydrops than the cochlea and utricle(16/26, 61.5%; 14/26, 53.8%), and two radiologists had a very good agreement on the location of endolymphatic hydrops( kappa =0.820). Moreover, there was a significantly statistical difference between the affected and healthy area of the endolymphatic space in this study ( P< 0.01). Conclusion: The technique of 3D-FLAIR MR imaging through single dose intravenous gadolinium injection is feasible, which can estimate endolymphatic hydrops in patients with otogenic vertigo, and accurately classify the degree of hydrops.

Programmed deformations are widespread in nature, providing elegant paradigms to design self-morphing materials with promising applications in biomedical devices, flexible electronics, soft robotics, etc. In this emerging field, hydrogels are an ideal material to investigate the deformation principle and the structure-deformation relationship. One crucial step is to construct heterogeneous structures in a facile yet effective way. Herein, we provide a focus review on different deformation modes and corresponding structural features of hydrogels. Photolithography is a versatile approach to control the outer shape of the hydrogel and spatial distribution of the component in the hydrogel, endowing the patterned hydrogels with programmed internal stress and thus controllable deformations. Specifically, cooperative deformations take place in periodically patterned hydrogels with in-plane gradients, and multiple morphing structures are formed in one patterned hydrogel using selective preswelling to direct the buckling of each unit. The structural control strategy and deformation principles should be applicable to other materials with broad applications in diverse areas., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research. We evaluated 18 animals with malignancies (16 lymphomas, one fibrosarcoma and one carcinoma) and 32 controls. We developed real time quantitative PCR assays for each gammaherpesvirus DNA viral load (VL) in malignant and non-tumor tissues; we also characterized the tumors using immunohistochemistry and in situ hybridization. Furthermore, we retrospectively quantified gammaherpesvirus DNA VL and SIV/SHIV RNA VL in longitudinally-collected PBMCs and plasma, respectively. One or more gammaherpesviruses were detected in 17 tumors; generally, one was predominant, and the relevant DNA VL in the tumor was very high compared to surrounding tissues. RLCV was predominant in tumors resembling diffuse large B cell lymphomas; in a Burkitt-like lymphoma, RRV was predominant; and in the fibrosarcoma, RFHV was predominant. Median RRV and RLCV PBMC DNA VL were significantly higher in cases than controls; SIV/SHIV VL and RLCV VL were independently associated with cancer. Local regressions showed that longitudinal VL patterns in cases and controls, from SIV infection to necropsy, differed for each gammaherpesvirus: while RFHV VL increased only slightly in all animals, RLCV and RRV VL increased significantly and continued to increase steeply in cases; in controls, VL flattened. In conclusion, the data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses., Competing Interests: The authors have declared that no competing interests exist.

Mouret abscess is a rare extracranial complication of suppurative otitis media. It is generally believed to be a deep neck abscess caused by inflammation leading to the rupture of the bony tip of the mastoid tip. The location of Mouret abscess is deep. The symptoms are insidious at the onset, but may eventually spread to the surrounding tissue, and even lead to mediastinal abscess, cavernous sinus thrombosis, meningitis, dyspnea and other serious complications. At present, with the popularization of antibiotics, the occurrence rate of Mouret abscess is very low, and only sporadic cases have been reported.In this paper, a case of Mouret abscess caused by cholesteatoma was analyzed to explore Mouret abscess in terms of the route of infection, clinical manifestations, imaging features, diagnosis and treatment., 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© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: The metastasis of axillary lymph node (ALNs) is a critical step in the initial cancer staging of newly diagnosed breast cancer (BC) patients. Various imaging modalities can enhance the sensitivity of clinical examination in assessing the ALN status., Patients and Methods: We enrolled 135 patients with BC, confirmed via histopathology, including 4 bilateral BC cases. A total of 139 ipsilateral ALNs adjacent to the breast lesion were examined via physical examination, ultrasonography (US), and magnetic resonance imaging (MRI); of these, 100 were nonpalpable ALNs, as determined by experienced breast surgeons and physicians. The relative size parameters on MRI and US images were recorded. Receiver operating characteristic (ROC) analyses were conducted, and the area under the ROC curve (AUC) was compared., Results: Of 139 ALNs, 67 (48%) were malignant and 72 (52%) were benign on pathological examination. In all of the ALNs, the US short diameter appeared to be the most discriminative quantitative measurement for detecting positive findings (AUC, 0.854). In nonpalpable ALNs as well, the US short diameter exhibited the greatest discriminability (AUC, 0.746). However, the 2-dimensional and 3-dimensional parameters on MRI did not exhibit any significant differences between the enrolled and nonpalpable ALNs (P > .05)., Conclusion: The shortest diameter on US exhibited better discriminative ability than MRI for predicting positive ALNs in nonpalpable axillae. Moreover, the 2-dimensional and 3-dimensional parameters on MRI did not differ in terms of discriminability., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the long-term efficacy of endolymphatic sac mastoid drainage for Ménière disease. Method: Data from 26 patients diagnosed with MD strictly meeting the criteria issued by " Guideline of diagnosis and treatment of Meniere disease(2017)" from 2006 to 2015 were analyzed in this study.Endolymphatic sac mastoid shunt surgery was performed for each patient.The therapeutic effect was evaluated against the " Guideline of diagnosis and treatment of Meniere disease(2017)".Vertigo control and auditory function were measured after at least two years follow up. Result: In 26 cases,16 cases were male and 10 cases were femaleThe age ranged from 24 to 71 years old,with an average of 52.04 years.The disease duration ranged from 1 to 32 years.22 cases were diagnosed as unilateral Ménière disease,and bilateral involvement was identified in 4 cases,thus a total of 30 ears were included.According to the preoperative staging of hearing,there were 0 cases in stage one,5 cases in stage two,16 in stage three and 9 cases in stage four.15 cases(57.7%)achieved class A vertigo conrol(complete control),9 cases(34.6%)class B(substantial control)and 2 cases(7.7%)class D(no control).The severity of vertigo and its impact on daily life were improved in 24 cases(92.3%)with a score of 0 point,and 2 cases(7.7%)scored 2 points.Post-operative hearing was improved in 3 cases(11.5%),unchanged in 16 cases(61.6%)and worsened in 7 cases(26.9%).After operation,tinnitus disappeared in 5 cases(19.2%),reduced in 13 case(50%)and unchanged in 8 cases(30.8%). Conclusion: Endolymphatic sac mastoid drainage was an effective and safe management for intractable Ménière disease patients with pre-operative residual hearing.The occurrence of complication was unsual.The patients who are in stage four could gain benifits from the surgery.

Objective: To analyze characteristics of CT scan and MRI images of middle ear adenomas,and provide pre-operation diagnosis and differential diagnosis combined with clinical manifestation. Method: Retrospective analysis of 8 cases of middle ear adenomas which were diagnosed and treated with surgery in Beijing Tongren Hospital between 2004 and 2014, patients' complain, clinical manifestation, physical examination, pure tone analysis, CT scan and MRI images were collected. Result: A total of 8 cases were included in this study with 5 females and 3 males. Age of onset ranged from 21 to 51 years old, with an average age of 37.5 years old, and middle age of 37 years old. All patients suffered from single side middle ear adenomas, 5 of left side and 3 of right side. All 8 patients suffered from hearing loss with tinnitus or stuffy feelings, 2 cases with otalgia, 1 with facial nerve paralysis. Physical examination showed 5 cases of bulging of tympanic membrane, 2 cases of out growth of mass into the external ear canal, and 1 with normal tympanic membrane. CT scan of 7 patients showed mass in tympanum and mastoid, with packaged ossicular chain and with no significant bone damage. 2 cases showed out growth of mass into the external ear canal, and 1 case showed limited mass in middle tympanum. MRI images of 5 cases showed equal T1 and T2 signals with intensifying in tympanum. Long T1 or equal T1 and long T2 signal in mastoid showed obstructive inflammation. Conclusion: Characters of middle ear adenomas includes mass in tympanum without bone damage in CT scan, and equal T1 and T2 signal with significant intensifying in tympanum in MRI images. Combined with clinical manifestation, this radiological information may provide benefit for pre-operation diagnosis., 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© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To identify the audiological improvement postoperatively and improve the understand of otosclerosis for a better performance of personalized surgical treatment. Method: We retrospectively reviewed a series of 200 cases after surgery for ototsclerosis.The clinical characteristics,pre-and postoperative audiometric results,signs of Carhart notch, Gelle test and the characteristics of high-resolution computed tomography of temporal bone were analyzed retrospectively. Result: 73% of patients had tinnitus, while 4% had sense of ear fullness,80.79% had Carhart notch,92.09% had negative result in Gelle test and 45.66% had positive signs on computed tomography. 68% of the patients revealed a type A tympanogram with only 22% type As.Fifty-six cases with laser stapedotomy achieved a the air bone gap at 250 Hz,500 Hz,1 kHz,2 kHz and 4 kHz of 25.54,16.25,13.75,6.34,15.96 dB,respectively. The bone conduction thresholds at 250 Hz,500 Hz,1 kHz,2 kHz improved 2.05,1.51,3.75 and 3.93 dB,respectively. At 4 kHz, bone conduction threshold increased by 1.34 dB.The improvement of bone conduction threshold at 250 Hz,1 kHz,2 kHz was significantly but for the revisions at 500 Hz and 4 kHz. Conclusion: The diagnosis of otosclerosis should be based on the combination of medical history, pure tone audiometry, tympanometry, Carhart notch, Gelle test and high resolution computed tomography of temporal bone.Surgical technique of stapedotomy with Piston artificial auditory ossicle implantation could improve not only the air conduction threshold, but also the bone conduction threshold at 250 Hz,1 kHz,2 kHz., 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© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Catalpol, isolated from the roots of Rehmanniaglutinosa , Chinese foxglove, is an iridoid glycoside with antioxidant, anti-inflammatory and anti-hyperglycemic agent. The present study was to investigate the effects of catalpol on diabetic atherosclerosis in alloxan-induced diabetic rabbits. Diabetes was induced in rabbits by a hyperlipidemic diet and intravenous injection of alloxan (100 mg/kg). Rabbits were treated for 12 weeks. The fasting blood glucose, insulin, homeostasis model of insulin resistance, total cholesterol and triglyceride were measured. The thoracic aorta was excised for histology. The plasma and vascular changes including some markers of oxidative stress, inflammatory cytokines and fibrosis factors were examined. Plasma levels of fasting blood glucose, insulin and homeostasis model of insulin resistance were significantly decreased in catalpol group. Catalpol treatment ameliorated diabetic atherosclerosis in diabetic rabbits as demonstrated by significantly inhibited neointimal hyperplasia and macrophages recruitment. Catalpol treatment also enhanced the activities of superoxide dismutase, glutathione peroxidase, and increased the plasma levels of total antioxidant status, meanwhile reduced the levels of malondialdehyde, protein carbonyl groups and advanced glycation end product. Furthermore, catalpol also reduced circulating levels of tumor necrosis factor-α, monocyte chemotactic protein-1 and vascular cell adhesion molecule-1. Catalpol also decreased transforming growth factor-β1 and collagen IV mRNA and protein expressions in the vessels. Catalpol exerts an ameliorative effect on atherosclerotic lesion in alloxan-induced diabetic rabbits. The possible mechanisms may be related to inhibition of oxidative stress inflammatory response and anti-fibrosis and reduced aggregation of extracellular matrix.

Early after HIV infection there is substantial depletion of CD4 + T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I-V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4 + T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4 + T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4 + T cells after 96 weeks of cART.

A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB), even though the lymphoid tissues (LT) are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation in situ hybridization approach to detect vRNA, including vRNA+ cells and viral particles ("RNAscope"), vDNA+ cells ("DNAscope") and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section. RNAscope is highly sensitive with greater speed of analysis compared to traditional in situ hybridization. The highly sensitive and specific DNAscope detected SIV/HIV vDNA+ cells, including duplexed detection of vDNA and vRNA or immunophenotypic markers in the same section. Analysis of LT samples from macaques prior to and during combination antiretroviral therapy demonstrated that B cell follicles are an important anatomical compartment for both latent and active viral persistence during treatment. These new tools should allow new insights into viral reservoir biology and evaluation of cure strategies.

Disruption of the mucosal epithelium during lentivirus infections permits translocation of microbial products into circulation, causing immune activation and driving disease. Although the liver directly filters blood from the intestine and is the first line of defense against gut-derived antigens, the effects of microbial products on the liver are unclear. In livers of normal macaques, minute levels of bacterial products were detectable, but increased 20-fold in simian immunodeficiency virus (SIV)-infected animals. Increased microbial products in the liver induced production of the chemoattractant CXCL16 by myeloid dendritic cells (mDCs), causing subsequent recruitment of hypercytotoxic natural killer (NK) cells expressing the CXCL16 receptor, CXCR6. Microbial accumulation, mDC activation, and cytotoxic NK cell frequencies were significantly correlated with markers of liver damage, and SIV-infected animals consistently had evidence of hepatitis and fibrosis. Collectively, these data indicate that SIV-associated accumulation of microbial products in the liver initiates a cascade of innate immune activation, resulting in liver damage., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis.

CUEDC2, a CUE-domain-containing protein, modulates inflammation, but its involvement in tumorigenesis is still poorly understood. Here, we report that CUEDC2 is a key regulator of macrophage function and critical for protection against colitis-associated tumorigenesis. CUEDC2 expression is dramatically upregulated during macrophage differentiation, and CUEDC2 deficiency results in excessive production of proinflammatory cytokines. The level of CUEDC2 in macrophages is modulated by miR- 324-5p. We find that Cuedc2 KO mice are more susceptible to dextran-sodium-sulfate-induced colitis, and macrophage transplantation results suggest that the increased susceptibility results from the dysfunction of macrophages lacking CUEDC2. Furthermore, we find that Cuedc2 KO mice are more prone to colitis-associated cancer. Importantly, CUEDC2 expression is almost undetectable in macrophages in human colon cancer, and this decreased CUEDC2 expression is associated with high levels of interleukin-4 and miR-324-5p. Thus, CUEDC2 plays a crucial role in modulating macrophage function and is associated with both colitis and colon tumorigenesis., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections induce robust, generalized inflammatory responses that begin during acute infection and lead to pathological systemic immune activation, fibrotic damage of lymphoid tissues, and CD4⁺ T-cell loss, pathogenic processes that contribute to disease progression., Methods: To better understand the contribution of tumor necrosis factor (TNF), a key regulator of acute inflammation, to lentiviral pathogenesis, rhesus macaques newly infected with SIVmac239 were treated for 12 weeks in a pilot study with adalimumab (Humira), a human anti-TNF monoclonal antibody., Results: Adalimumab did not affect plasma SIV RNA levels or measures of T-cell immune activation (CD38 or Ki67) in peripheral blood or lymph node T cells. However, compared with untreated rhesus macaques, adalimumab-treated rhesus macaques showed attenuated expression of proinflammatory genes, decreased infiltration of polymorphonuclear cells into the T-cell zone of lymphoid tissues, and weaker antiinflammatory regulatory responses to SIV infection (ie, fewer presumed alternatively activated [ie, CD163⁺] macrophages, interleukin 10-producing cells, and transforming growth factor β-producing cells), along with reduced lymphoid tissue fibrosis and better preservation of CD4⁺ T cells., Conclusions: While HIV/SIV replication drives pathogenesis, these data emphasize the contribution of the inflammatory response to lentiviral infection to overall pathogenesis, and they suggest that early modulation of the inflammatory response may help attenuate disease progression.

Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here we used comprehensive approaches (ie, FACS sorting, quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4(+) T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV-infected humans, and SIVsmm-infected sooty mangabeys (SMs). We find: (1) infection frequencies among CD4(+) T cells in chronically SIV-infected RMs are significantly higher than those in SIVsmm-infected SMs; (2) infected cells are found in distinct anatomic LT niches and different CD4(+) T-cell subsets in SIV-infected RMs and SMs, with infection patterns of RMs reflecting HIV infection in humans; (3) T(FH) cells are infected at higher frequencies in RMs and humans than in SMs; and (4) LT viral burden, including follicular dendritic cell deposition of virus, is increased in RMs and humans compared with SMs. These data provide insights into how natural hosts are able to maintain high levels of plasma viremia while avoiding development of immunodeficiency.

Objective: To explore the feasibility of sentinel lymph node biopsy in peri-neoadjuvant chemotherapy for breast cancer patients., Methods: A total of 252 breast cancer patients underwent sentinel lymph node biopsy and axillary lymph node dissection from January 2005 to November 2011, including 150 patients in pre-neoadjuvant chemotherapy group and 102 in post-neoadjuvant chemotherapy group. The feasibility of sentinel lymph node biopsy under different clinical states of axillary lymph node was compared., Results: No significant difference was found in the detection rate (98.5% vs 92.8%), false negative rate (6.7% vs 7.9%), accuracy (98.4% vs 91.9%) and negative sensitivity (97.9% vs 88.0%) of sentinel lymph node biopsy before neoadjuvant chemotherapy whether the axillary lymph node was negative or positive. However, the transfer rate of sentinel lymph node in the positive group was significantly higher than the negative group (28.8% vs 67.5%, P = 0.000). False negative rate of sentinel lymph node in biopsy was significantly higher in the post-neoadjuvant chemotherapy group than the pre-neoadjuvant chemotherapy group (7.5% vs 23.9%, P = 0.024) and the accuracy/negative sensitivity decreased significantly (95.1% vs 83.5%, P = 0.005/94.4% vs 75.0%, P = 0.003). No statistical difference existed in the detection rate, false negative rate, accuracy, negative sensitivity of sentinel lymph node in biopsy before and after neoadjuvant chemotherapy in patients with negative axillary lymph node for a preliminary diagnosis. The accuracy of sentinel lymph node decreased significantly in biopsy after neoadjuvant chemotherapy in patients with positive axillary lymph node confirmed pathologically for a preliminary diagnosis compared with before (98.4/83.7%, P = 0.010), the transfer rate of sentinel lymph node increased significantly (28.8/53.7%, P = 0.005) and negative sensitivity reduced significantly (97.9/68.0%, P = 0.007); Compared with pre-neoadjuvant chemotherapy, the negative sensitivity decreased significantly in patients with axillary lymph node positive confirmed pathologically and then turned negative (94.4% vs 57.1%, P = 0.005) while the transfer rate of sentinel lymph node increased significantly (28.8%/65.0%, P = 0.003)., Conclusions: Sentinel lymph node before neoadjuvant chemotherapy may accurately predict axillary lymph node metastasis. The detection rate, false negative rate, accuracy, negative sensitivity of sentinel lymph node in biopsy after neoadjuvant chemotherapy in patients with negative axillary lymph node for preliminary diagnosis are the same before neoadjuvant chemotherapy. Patients with positive axillary lymph node for a preliminary diagnosis are unsuitable for sentinel lymph node biopsy whether axillary lymph node turns negative or not after neoadjuvant chemotherapy.

We demonstrate that few-layered graphene sheets used as a saturable absorber can provide efficient Q-switching and mode-locking modulation in 1.34 μm Nd:GdVO(4) bulk lasers. The minimum Q-switched pulses were 450 ns for 260 mW average power, 43 kHz repetition rate, and 2.5 μJ pulse energy. For the mode-locked laser, an average power of 1.29 W was achieved with 11 ps pulse duration and 13 nJ pulse energy. To our knowledge, this average power is the highest yet obtained from a graphene mode-locked laser, and the corresponding optical-optical efficiency of 23% is the best result among 1.3 μm neodymium mode-locked lasers. The quality factor M(2) of the Q-switched beam was 1.4 and 1.6 in the horizontal and longitudinal planes, respectively, and the M(2) of the mode-locked beam reached 1.1 and 1.0. These results clearly indicate the advantages of few-layered graphene as a saturable absorber.

Although xenotropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic in vivo infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential that is able to replicate in human cells. Here we describe a comprehensive analysis of two male pigtailed macaques (Macaca nemestrina) experimentally infected with XMRV. Following intravenous inoculation with >10(10) RNA copy equivalents of XMRV, viral replication was limited and transient, peaking at ≤2,200 viral RNA (vRNA) copies/ml plasma and becoming undetectable by 4 weeks postinfection, though viral DNA (vDNA) in peripheral blood mononuclear cells remained detectable through 119 days of follow-up. Similarly, vRNA was not detectable in lymph nodes by in situ hybridization despite detectable vDNA. Sequencing of cell-associated vDNA revealed extensive G-to-A hypermutation, suggestive of APOBEC-mediated viral restriction. Consistent with limited viral replication, we found transient upregulation of type I interferon responses that returned to baseline by 2 weeks postinfection, no detectable cellular immune responses, and limited or no spread to prostate tissue. Antibody responses, including neutralizing antibodies, however, were detectable by 2 weeks postinfection and maintained throughout the study. Both animals were healthy for the duration of follow-up. These findings indicate that XMRV replication and spread were limited in pigtailed macaques, predominantly by APOBEC-mediated hypermutation. Given that human APOBEC proteins restrict XMRV infection in vitro, human XMRV infection, if it occurred, would be expected to be characterized by similarly limited viral replication and spread.

CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte-depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell-mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.

High-quality graphene sheets with lateral size over 20 μm have been obtained by bath sonicating after subjecting the wormlike graphite marginally to mixed oxidizer. To date, to our knowledge, they are the largest graphene sheets prepared by exfoliation in the liquid phase. A saturable absorber mirror was fabricated based on these sheets. We exploited it to realize mode-locking operation in a diode-pumped Nd:GdVO(4) laser. A pulse duration of 16 ps was produced with an average power of 360 mW and a highest pulse energy of 8.4 nJ for a graphene mode-locked laser., (© 2011 Optical Society of America)

We demonstrated that the graphene could be used as an effective saturable absorber for Q-switched solid-state lasers. A graphene saturable absorber mirror was fabricated with large and high-quality graphene sheets deprived from the liquid phase exfoliation. Using this mirror, 105-ns pulses and 2.3-W average output power are obtained from a passively Q-switched Nd:GdVO(4) laser. The maximum pulse energy is 3.2 μJ. The slope efficiency is as high as 37% approximating to 40% of the continue-wave laser, indicating a low intrinsic loss of the graphene., (© 2011 Optical Society of America)

Objective: To analyze the clinical features and the surgical treatment outcomes of patients with tuberculous otitis media and mastoiditis., Methods: The medical records of 16 patients (18 ears) with tuberculous otitis media and mastoiditis, who received surgery in Beijing Tongren hospital, were reviewed., Results: The common symptoms were otorrhea and hearing loss, and 3 patients demonstrated severe sensorineural hearing loss. Three patients demonstrated a peripheral-type facial palsy. Temporal bone high resolution CT scans demonstrated the entire tympanum and mastoid air cells were occupied by soft tissue. Eleven patients demonstrated bone destruction and sequestra was found in 7 temporal bones. Contemporary pulmonary tuberculosis were diagnosed in 7 of the 16 patients. Surgical removal of disease lesions in combination with anti-tuberculosis treatment were given to 15 patients. Other than 2 cases of tuberculous otitis media and mastoiditis diagnosed by pre-operational biopsy through the perforated tympanic membrane, the remaining 14 cases were diagnosed intra-operatively or post-operatively. No relapse of tuberculosis in the middle ear and mastoid were found after follow-up for more than 1 year, except for the one case that was lost to follow-up. The 3 cases of facial nerve palsy almost recovered to normal., Conclusions: Clinicians should suspect tuberculous otitis media and mastoiditis if clinical findings include refractory otorrhea, total occupation of the tympanic cavity and mastoid ari cells by soft tissue, and erosion of the bone or sequestra as shown by CT. A history of tuberculosis should be asked carefully in order to differentiate tuberculous otitis media and mastoiditis. The patients who received surgery and anti-tuberculosis chemotherapy achieved more rapid healing of the ear.

Objective: To research the effects of chronic suppurative otitis media on bone conduction threshold in old patients., Methods: The files of patients with unilateral chronic otitis media were retrospective analyzed, who were all oder than 60 years, who were inpatient in our department since January 2005 to March 2009. Conventional puretone audiometry test was carried out. Bone conduction thresholds were calculated for frequencies of 0.5, 1, 2, and 4 kHz, with comparison between the ear with chronic otitis media and contralateral ear. Thresholds were examined separately for each frequency., Results: The bone conduction threshold for the normal side was lower than those for the ear with chronic otitis media. The threshold shift was statistically significant for each frequency (P < 0.01). There were no differences between the groups when analyzed for the presence of cholesteatoma except at 2 kHz frequencies (Z = -1.975, P = 0.048). There were differences between the groups when analyzed for an interruption of the ossicular chain only at 2 kHz frequencies (Z = -2.721, P = 0.007). There were differences between the groups when the duration of middle ear disease was not same at 1 kHz and 2 kHz frequencies (Z value were -2.877, -2.624, P < 0.01, respectively)., Conclusions: This study shows that chronic otitis media can enhance bone conduction threshold for old patients. All measures for early cure should be considered as early as possible in oder patients with chronic otitis media to prevent advance of sensorineural hearing loss.

Objective: To explore the therapeutic effect and acting mechanism of Huanglan Granule (HLG) on rubella virus (RuV)., Methods: Sixty patients with positive RuV-IgM were randomly assigned to two groups equally, the treatment group was medicated by HLG (one dosage per day, containing milkvetch root, isatis root and basket fern, each 30 g), while the control group by ribavirin (0.2 g, three times per day) for 20 days. The negative conversion rate of RuV-IgM and the serum levels of interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) were observed before and after treatment. Moreover, the in vitro inhibitory activity of HLG against RuV Gos line on cultured Vero cells was determined by cytopathic inhibition method., Results: The difference of negative conversion rate between the two groups after one course treatment was significant (86.7% vs 63.3%, P <0.05). However, it turned to insignificant after two courses of treatment (100% vs 86.7%, P >0.05). The serum level of IL-2 was lower and TNF-alpha was higher significantly in patients with positive RuV-IgM as compared with the normal range, and the two indexes returned to the normal range rapidly after HLG treatment. In vitro study showed that the inhibitory effect of HLG on RuV caused cellular change was evident., Conclusion: HLG has obvious inhibitory effect on RuV, both in vitro and in vivo, it can also raise the immunity of organism and thus it serves as a safe and effective Chinese medicine for treatment of active RuV infection.

An intrinsic plastic Cu(45)Zr(46)Al(7)Ti(2) bulk metallic glass (BMG) with high strength and superior compressive plastic strain of up to 32.5% was successfully fabricated by copper mold casting. The superior compressive plastic strain was attributed to a large amount of randomly distributed free volume induced by Ti minor alloying, which results in extensive shear band formation, branching, interaction and self-healing of minor cracks. The mechanism of plasticity presented here suggests that the creation of a large amount of free volume in BMGs by minor alloying or other methods might be a promising new way to enhance the plasticity of BMGs.

In this paper, we report the long-range ordering effect observed in the electro-crystallization of Zn and ZnO from an ultrathin aqueous electrolyte layer of ZnSO4 . The deposition branches are regularly angled, covered with random-looking, scalelike crystalline platelets of ZnO. Although the orientation of each crystalline platelet of ZnO appears random, transmission electron microscopy shows that they essentially possess the same crystallographic orientation as the single-crystalline zinc electrodeposit underneath. Based on the experimental observations, we suggest that this unique long-range ordering effect results from an epitaxial nucleation effect in electrocrystallization.

In this paper we report the spontaneous formation of a nanostructured film by electrodeposition from an ultrathin electrolyte layer of CuSO4. The film consists of straight periodic ditches and ridges, which corresponds to the alternating deposition of nanocrystallites of copper and copper plus cuprous oxide, respectively. The periodicity on the film may vary from 100 nm to a few hundred nanometers depending on the experimental conditions. In the formation of the periodically nanostructured film, oscillating voltage/current has been observed across the electrodes, and the frequency depends on the pH of the electrolyte and the applied current/voltage. A model based on the coupling of [Cu2+] and [H+] in the electrodeposition is proposed to describe the oscillatory phenomena in our system. The calculated results are in agreement with the experimental observations.

Background: p53 mutations are frequently observed in colorectal carcinomas but they have also been found in colorectal adenomas, although considerably less frequently., Aims: To explore p53 mutations in benign tumours, we have screened 70 colorectal adenomas for allelic loss at, and point mutations in, TP53 by analysis of selected microdissected cell populations., Results: Sixteen (22.8%) adenomas were found to have allelic loss, of which 11 (15.7%) had p53 mutations. In adenomas with mild, moderate, or severe dysplasia, mutation or allelic loss occurred in 4.8%, 16.7%, and 52.6%, respectively (p<0.001). Seven different mutations were found, all missense changes or inframe deletions: one (Thr150Arg) has not been found before while three (Gln144His, Gly245Arg, and Glu285Gln) have not been described previously in colorectal tumours. The other three mutations (Arg175Gly, DeltaPro190, and Gly245Ser) have been found in colorectal carcinomas, the last commonly. Adenomas harboured a spectrum of p53 mutations which was significantly different from cancers as regards the position in the gene and a higher frequency of G-->C/C-->G changes., Conclusions: Combining our data on adenomas with data already published and in comparison with the spectrum of mutations in colorectal carcinomas, it is suggested that some p53 mutations have a weaker effect than others and are therefore more likely to be found in adenomas which have not progressed to carcinomas.

The aberrant expression of beta-catenin in colon tumors and the discovery of beta-catenin mutations in small adenomas suggest that alterations of beta-catenin are early events in human colorectal carcinogenesis. Here, we describe the expression of beta-catenin in human aberrant crypt foci (ACF), the earliest identified neoplastic lesions in the colon. Paraffin-embedded sections of 94 ACF, 12 adenomas, and 10 carcinomas were evaluated for beta-catenin expression by immunohistochemistry. Normal colonic epithelial cells adjacent to these lesions showed strong membranous expression of beta-catenin and lacked cytoplasmic and nuclear expression. Cytoplasmic expression of beta-catenin was seen in 25 of 46 ACF with dysplasia and in 2 of 48 ACF with atypia. In ACF with dysplasia, reduced membranous expression of beta-catenin was associated with increased nuclear (P = 0.0013) and cytoplasmic (P = 0.0247) expression. The membranous (P = 0.0003) expression of beta-catenin was reduced, and the cytoplasmic (P = 0.0016) and nuclear (P = 0.0266) expressions increased in ACF according to their degree of dysplasia. Likewise, membranous (P = 0.0007) expression of beta-catenin was reduced, and the cytoplasmic (P = 0.0050) and nuclear (P = 0.0001) expressions increased from ACF to adenoma to carcinoma. These data suggest that ACF and their aberrant expression of beta-catenin play a role in colon tumorigenesis.

Aberrant crypt foci (ACF) are the earliest identified neoplastic lesions in the colon. Aberrant expression of inducible nitric oxide synthase (iNOS or NOS2) has been documented in colorectal tumors, but expression of iNOS has not been reported in human ACF or multiple neoplastic lesions from the same patient. Immunohistochemical expression of iNOS was evaluated in 42 ACF, 14 adenomas, and 25 carcinomas and their adjacent normal mucosa. iNOS was strongly expressed in the normal colonic epithelial cells of all patients; it was markedly reduced in 21 of 42 (50%) ACF and in 14 of 25 (56%) carcinomas. The expression of iNOS was remarkably similar in multiple lesions from the same patient (P < 0.0001). These results suggest that the reduced expression of iNOS is a very early event in the development of some human colorectal tumors, and that host factors control the expression of iNOS similarly in premalignant and malignant colonic epithelial cells.

Abnormal expression of the fragile histidine triad (FHIT) candidate tumor suppressor gene has been observed in a variety of human tumors, but little is known about its expression during colorectal tumorigenesis. Sections of 70 aberrant crypt foci (ACF), 55 adenomas, 84 primary colorectal carcinomas, and 13 metastatic lesions were evaluated immunohistochemically for Fhit expression. All normal colonic epithelium showed a strong expression of Fhit; 44% of carcinomas showed a marked loss or absence of Fhit expression. The proportion of carcinomas with reduced expression showed an increasing trend (a) with decreasing differentiation and (b) in tumors with metastases (62%) compared with tumors without metastases (38%). The proportion of metastatic lesions (12 of 13) with reduced expression of Fhit was even greater. Although only a small proportion of ACF and adenomas showed a reduction of Fhit expression, the reduced expression of Fhit was strongly associated with the degree of dysplasia in both ACF (P = 0.0002) and adenomas (P = 0.0085). The findings of reduced expression of Fhit in a small proportion of colonic precancerous lesions and in increased proportions of primary and metastatic colorectal cancers suggest that Fhit plays a role in the development and progression of some colon carcinomas.