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Background: Breast cancer is the most prevalent malignant tumor among women, with hormone receptor-positive cases constituting 70%. Fulvestrant, an antagonist for these receptors, is utilized for advanced metastatic hormone receptor-positive breast cancer. Yet, its inhibitory effect on tumor cells is not strong, and it lacks direct cytotoxicity. Consequently, there's a significant challenge in preventing recurrence and metastasis once cancer cells develop resistance to fulvestrant., Method: To address these challenges, we engineered tumor-targeting nanoparticles termed 131 I-fulvestrant-ALA-PFP-FA-NPs. This involved labeling fulvestrant with 131 I to create 131 I-fulvestrant. Subsequently, we incorporated the 131 I-fulvestrant and 5-aminolevulinic acid (ALA) into fluorocarbon nanoparticles with folate as the targeting agent. This design facilitates a tri-modal therapeutic approach-endocrine therapy, radiotherapy, and PDT for estrogen receptor-positive breast cancer., Results: Our in vivo and in vitro tests showed that the drug-laden nanoparticles effectively zeroed in on tumors. This targeting efficiency was corroborated using SPECT-CT imaging, confocal microscopy, and small animal fluorescence imaging. The 131 I-fulvestrant-ALA-PFP-FA-NPs maintained stability and showcased potent antitumor capabilities due to the synergism of endocrine therapy, radiotherapy, and CR-PDT. Throughout the treatment duration, we detected no notable irregularities in hematological, biochemical, or histological evaluations., Conclusion: We've pioneered a nanoparticle system loaded with radioactive isotope 131 I, endocrine therapeutic agents, and a photosensitizer precursor. This system offers a combined modality of radiotherapy, endocrine treatment, and PDT for breast cancer., (© 2024. The Author(s).)

Two previously undescribed dihydrophenanthrene derivatives ( 1 and 2 ) were isolated along with twelve known analogues from the whole plant of Dendrobium terminale . The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis. The NMR data of known phenanthrene derivatives ( 7 and 9 ) were revised by 2D NMR. The isolated compounds were evaluated for cytotoxicity against three kinds of tumor cell lines (sw1990, HCT-116, and HepG2). Especially compounds 11 and 14 showed stronger antitumor effects, and the structure-activity relationship of these compounds was discussed.

Finlets have a unique overhanging structure at the back, similar to a flag. They are located between the dorsal/anal fin and the caudal fin on the sides of the body. Until now, the sensing ability of finlets has not been well understood. In this paper, we design and manufacture a biomimetic soft robotic finlet (48.5 mm long, 30 mm high) with mechanosensation based on printed stretchable liquid metal sensors. The robotic finlet's posterior fin ray can achieve side-to-side movement orthogonal to the anterior fin ray. A flow sensor encapsulating a liquid metal sensor network enables the biomimetic finlets to sense the direction and flow intensity. The stretchable liquid metal sensors mounted on micro-actuators are utilized to perceive the swing motion of the fin ray. We found that the finlet prototype can sense the flapping amplitudes and frequency of the fin ray. The membrane between the two orthogonal fin rays can amplify the sensor output. Our results indicate that the overhanging structure endows the biomimetic finlet with the ability to sense external stimuli from stream-wise, lateral and vertical directions. We further demonstrate, through digital particle image velocimetry experiments, that the finlet can detect a Kármán vortex street. This study lays the foundations for exploring the environmental perception of biological fish fins and provides a new approach for the perception of complex flow environments by future underwater robots., (© 2021 IOP Publishing Ltd.)

Sensory cues play an important role in any plant-animal interaction. Yet, we know very little about the cues used by wild mammals during fruit selection. Existing evidence mainly comes from captive studies and suggests that the pteropodid bats rely on olfaction to find fruits. In this study, we avoided captivity-generated stressors and provide insights from natural selective forces by performing manipulative experiments on free-ranging fruit bats (Cynopterus sphinx) in a wild setting, in a tree species that exhibits a bat-fruit syndrome (Madhuca longifolia var. latifolia). We find that visual cues are necessary and sufficient to locate ripe fruits. Fruit experiments exhibiting visual cues alone received more bat visits than those exhibiting other combinations of visual and olfactory cues. Ripe fruit extractions were higher by bats that evaluated fruits by perching than hovering, indicating an additional cue, i.e., haptic cue. Visual cues appear to be informative over short distances, whereas olfactory and haptic cues facilitate the fruit evaluation for those bats that used hovering and perching strategies, respectively. This study also shows that adult bats were more skillful in extracting ripe fruits than the young bats, and there was a positive correlation between the weight of selected fruits and bat weight. This study suggests that the integration of multimodal cues (visual, olfactory and haptic) facilitate ripe-fruit localization and extraction in free-ranging pteropodid bats., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this paper, an efficient approach to extract total flavonoids (TFs) from Selaginella involvens (Sw.) Spring using homogenate-ultrasound-assisted ionic liquid (IL) extraction (HUA-ILE) was first developed. The results indicated that EPyBF 4 was selected as the suitable extractant. According to the single factor experiment and response surface methodology, the IL concentration of 0.10 mol/L, the extraction time of 160 s, the liquid/solid ratio of 13:1 mL/g, and the extraction power of 300 W were concluded as the best conditions. A yield of 8.48 ± 0.27 mg/g TF content was obtained. Compared with HUA ethanol extraction, ultrasound-assisted IL extraction, and percolation extraction, the TF content obtained by the HUA-ILE method could be increased by 2 to 4 times, and the extraction time could be reduced by 100 times. Furthermore, 16 compounds of the TF extract were finally identified through ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, among which 11 compounds were first discovered in S. involven . The contents of six biflavonoids in S. involven were determined simultaneously adopting high-performance liquid chromatography, including amentoflavone, hinokiflavone, bilobetin, ginkgetin, isoginkgetin, and heveaflavone. The TF extract in S. involven was proved to have potent antioxidant activity through the four antioxidant experiments. In conclusion, HUA-ILE was applied for the first time to exploit a green, efficient, and novel approach to extract TFs, and the research also provided promising prospects for applications of S. involven ., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

We report the disease characteristics, diagnosis, and treatment of granulomatous orchitis. A 38-year-old man presented with a history of intermittent swelling, pain, and discomfort in the right testicle of 3 days' duration. Unenhanced magnetic resonance imaging (MRI) of the testis and scrotum revealed an oval mass in the right testis measuring approximately 17 mm in diameter, with clear borders and a target ring-like appearance from periphery to center. T1-weighted imaging (T1WI) showed uniform low-intensity signals, and T2WI showed mixed high- and low-intensity signals. Diffusion-weighted imaging (DWI) signals were iso-intense, and the outer ring on enhanced scans showed progressive enhancement. We performed radical resection of the right testis under combined spinal-epidural anesthesia. The pathological diagnosis was granulomatous right orchitis. Two months postoperatively, ultrasonography showed no testis and epididymal echo signals in the right scrotum, and no obvious abnormalities; color Doppler blood flow imaging (CDFI) findings were normal. Granulomatous orchitis is rare in clinical practice, and the cause is unknown. The disease involves non-specific inflammation; however, it is currently believed that antibiotics and steroids are ineffective for conservative treatment, and orchiectomy should be actively performed.

Objectives: In the present study, we introduced a practical approach to quantify organ-specific radiation doses and investigated whether low-dose head circumference (HC)-based protocols for non-enhanced head computed tomography (CT) could reduce organs-specific radiation dose in pediatric patients while maintaining high image quality., Methods: A total of 83 pediatric patients were prospectively recruited. Without limits to the HC, 15 patients were selected as a convention group (CON group) and underwent non-enhanced head CT scan with standard-dose protocols (tube current-time products of 250mAs). Low-dose group (LD group), including remaining 68 pediatrics were divided into 3 subgroups based on the HC: 54.1-57.0 cm for LD 200mAs group (HC-based protocols of 200mAs), 51.1-54.0 cm for LD 150mAs group (HC-based protocols of 150mAs), 48.1-51.0 cm for LD 100mAs group (HC-based protocols of 100mAs). Subjective and objective image quality was evaluated and measured by 2 experienced radiologists. Radimetrics was used to calculate organs-specific radiation dose, including the brain, eye lenses, and salivary glands., Results: In CON 250mAs group, radiation doses in the brain and salivary glands were conversely correlated with HC, and pediatric patients with smaller HC received higher organs-specific radiation dose. Reducing tube current-time product from 250 to 100mAs could significantly reduce the organ-specific radiation dose. The subjective image quality score ≥ 3.0 is acceptable for diagnosis purposes. The signal to noise ratio (SNR) and the contrast to noise ratio (CNR) of bilateral thalamus and centrum semiovale in 3 LD subgroups were not statistically different compared with the CON group., Conclusion: Our research indicated that low-dose HC-based protocols of non-enhanced head CT scan can evidently reduce the organ-specific radiation doses, while maintaining high image quality. HC can serve as a vital tool to guide personalized low-dose head CT scan for pediatric patients., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

In December 2019, a pneumonia outbreak of unknown etiology was reported which caused panic in Wuhan city of central China, which was later identified as Coronavirus disease (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the Chinese Centre for Disease Control and Prevention (CDC) and WHO. To date, the SARS-CoV-2 spread has already become a global pandemic with a considerable death toll. The associated symptoms of the COVID-19 infection varied with increased inflammation as an everyday pathological basis. Among various other symptoms such as fever, cough, lethargy, gastrointestinal (GI) symptoms included diarrhea and IBD with colitis, have been reported. Currently, there is no sole cure for COVID-19, and researchers are actively engaged to search out appropriate treatment and develop a vaccine for its prevention. Antiviral for controlling viral load and corticosteroid therapy for reducing inflammation seems to be inadequate to control the fatality rate. Based on the available related literature, which documented GI symptoms with diarrhea, inflammatory bowel diseases (IBD) with colitis, and increased deaths in the intensive care unit (ICU), conclude that dysbiosis occurs during SARS-COV-2 infection as the gut-lung axis cannot be ignored. As probiotics play a therapeutic role for GI, IBD, colitis, and even in viral infection. So, we assume that the inclusion of studies to investigate gut microbiome and subsequent therapies such as probiotics might help decrease the inflammatory response of viral pathogenesis and respiratory symptoms by strengthening the host immune system, amelioration of gut microbiome, and improvement of gut barrier function., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Selaginella tamariscina , a traditional Chinese medicine, contains a variety of bioactive components, among which biflavonoids are the main active ingredients and have antioxidant, antitumor, and anti-inflammatory properties. In this study, ultrasonic-assisted ionic liquid extraction (UAILE) is used for the first time to extract two main biflavonoids (amentoflavone (AME) and hinokiflavone (HIN)) from S. tamariscina . A high-performance liquid chromatography method is used for the simultaneous determination of AME and HIN in S. tamariscina . Then, three novel ILs are synthesized for the first time by a one-step method using benzoxazole and three acids or acid salts as raw materials, and the structures of the synthesized ILs are characterized by elemental analysis, infrared spectroscopy, and NMR spectroscopy, as well as the thermal stability of the ILs is evaluated by thermogravimetric analysis. After screening the extraction effects of three benzoxazole ILs, three pyridine ILs, and three imidazole ILs, it is found that [Bpy]BF 4 is the best and therefore selected as the extractant. The optimal extraction process is explored in terms of the yields of AME and HIN from S. tamariscina by a single-factor experiments and response surface analysis. Under the optimal level of each influencing factor (IL concentration of 0.15 mol/L, solid-liquid ratio of 1:12 g/mL, ultrasonic power of 280 W, ultrasonic time of 30 min, and three extraction cycles), the extraction rates of AME and HIN from S. tamariscina are 13.51 and 6.74 mg/g, respectively. Moreover, the recovery experiment of [Bpy]BF 4 on the extraction of biflavonoids shows that the recovered IL can repeatedly extract targets six times and the extraction rate is about 90%, which indicates that the IL can be effectively reused. UAILE can effectively and selectively extract AME and HIN, laying the foundation for the application of S. tamariscina ., Competing Interests: The authors declare no competing financial interest., (© 2020 The Authors. Published by American Chemical Society.)

The clinical application of doxorubicin (DOX) for cancer treatment is limited due to its cardiotoxicity. However, the basic pathophysiological molecular mechanisms underlying DOX-induced cardiomyopathy have not yet been completely clarified, and the disease-specific therapeutic strategies are lacking. The aim of the present study was to investigate the potential cardioprotective effect of cardamonin (CAR), a flavone found in Alpinia plant, on DOX-induced cardiotoxicity in a mouse model. At first, in DOX-treated mouse cardiomyocytes, CAR showed significantly cytoprotective effects through elevating nuclear factor erythroid-2 related factor 2 (Nrf2) signaling, and reducing the degradation of Nrf2. This process then improved the anti-oxidant system, as evidenced by the up-regulated expression levels of haem oxygenase-1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). In contrast, DOX-induced increases in malondialdehyde (MDA) and reactive oxygen species (ROS) were highly inhibited by CAR treatments. Additionally, DOX-induced apoptosis and inflammatory response in cardiomyocytes were diminished by CAR through reducing the Caspase-3 and nuclear factor-κB (NF-κB) signaling pathways, respectively. Then, in the DOX-induced animal model with cardiotoxicity, we confirmed that through improving Nrf2 signaling, CAR markedly suppressed oxidative stress, apoptosis and inflammatory response in hearts of mice, improving cardiac function eventually. Together, our findings demonstrated that CAR activated Nrf2-related cytoprotective system, and protected the heart from oxidative damage, apoptosis and inflammatory injury, suggesting that CAR might be a potential therapeutic strategy in the prevention of DOX-associated myocardiopathy., (Copyright © 2019. Published by Elsevier Masson SAS.)

Transcription factors (TFs) like a nuclear factor of activated T-cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, damage by tumor-associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T-cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype. Moreover, the relationship between C/N and gut microbiome in CRC, especially role of NFAT and toll-like receptor signaling in regulating intestinal microbiota are also discussed. Furthermore, this review will discuss the proteins and genes relating to C/N induced acidosis in CRC, which includes ASIC2 regulated C/N1 and TFs associated with the glycolytic by-product that affect T-cell functions and CRC cell growth. It is revealed that calcineurin or NFAT targeting to antitumor, selective calcineurin inhibition or targets in NFAT signaling may be useful for clinical treatment of CRC. This can further aid in the identification of specific targets via cancer patient-personalized approach. Future studies should be focused on targeting to C/N or TLR signaling by the combination of therapeutic agents to regulate T-cell functions and gut microbiome for activating potent anticancer property with the prospect of potentiating the antitumor therapy for CRC., (© 2019 Wiley Periodicals, Inc.)

The basic helix-loop-helix (bHLH) family is the second largest superfamily of transcription factors that belongs to all three eukaryotic kingdoms. The key function of this superfamily is the regulation of growth and developmental mechanisms in plants. However, the bHLH gene family in Carthamus tinctorius has not yet been studied. Here, we identified 41 bHLH genes in Carthamus tinctorius that were classified into 23 subgroups. Further, we conducted a phylogenetic analysis and identified 10 conserved protein motifs found in the safflower bHLH family. We comprehensively analyzed a group of bHLH genes that could be associated with flavonoid biosynthesis in safflower by gene expression analysis, gene ontology annotation, protein interaction network prediction, subcellular localization of the candidate CtbHLH40 gene, and real-time quantitative expression analysis. This study provides genome-wide identification of the genes related to biochemical and physiological processes in safflower.

Ventricular restraint therapy is a non-transplant surgical option for the management of advanced heart failure (HF). To augment the therapeutic applications, it is hypothesized that ASD shows remarkable capabilities not only in delivering stem cells but also in dilated ventricles. Male SD rats were divided into four groups (n = 6): normal, HF, HF + ASD, and HF + ASD-BMSCs respectively. HF was developed by left anterior descending (LAD) coronary artery ligation in all groups except normal group. Post-infarcted electrocardiography (ECG) and brain natriuretic peptide (BNP) showed abnormal heart function in all model groups and HF + ASD-BMSCs group showed significant improvement as compared to other HF, HF + ASD groups on day 30. Masson's trichrome staining was used to study the histology, and a large blue fibrotic area has been observed in HF and HF + ASD groups and quantification of fibrosis was assessed. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. The mechanical function of the heart such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate was brought to normal when treated with ASD-BMSCs. This effect was more prominent than that of ASD therapy alone. In comparison to HF group, the SD rats in HF + ASD-BMBCs group showed a significant decline in BNP levels. So ASD can deliver BMSCs to the cardiomyocytes successfully and broaden the therapeutic efficacy, in comparison to the restraint device alone. An effective methodology to manage the end-stage HF has been proved.

Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T-cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy. Furthermore, this work is further to understand the complex interactions between the immune surveillance and develop resistance in tumor cells. As expected, if the promise of these developments is fulfilled, it could develop the effective therapeutic strategies and novel combinations to overcome immune resistance and enhance effector responses, which guide clinicians toward a more "personalized" treatment for advanced CRC patients., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Complicated pathophysiological syndrome associated with irregular functioning of the heart leading to insufficient blood supply to the organs is linked to congestive heart failure (CHF) which is the leading cause of death in developed countries. Numerous factors can add to heart failure (HF) pathogenesis, including myocardial infarction (MI), genetic factors, coronary artery disease (CAD), ischemia or hypertension. Presently, most of the therapies against CHF cause modest symptom relief but incapable of giving significant recovery for long-term survival outcomes. Unfortunately, there is no effective treatment of HF except cardiac transplantation but genetic variations, tissue mismatch, differences in certain immune response and socioeconomic crisis are some major concern with cardiac transplantation, suggested an alternate bridge to transplant (BTT) or destination therapies (DT). Ventricular restraint therapy (VRT) is a promising, non-transplant surgical treatment wherein the overall goal is to wrap the dilated heart with prosthetic material to mechanically restrain the heart at end-diastole, stop extra remodeling, and thereby ultimately improve patient symptoms, ventricular function and survival. Ventricular restraint devices (VRDs) are developed to treat end-stage HF and BTT, including the CorCap cardiac support device (CSD) (CSD; Acorn Cardiovascular Inc, St Paul, Minn), Paracor HeartNet (Paracor Medical, Sunnyvale, Calif), QVR (Polyzen Inc, Apex, NC) and ASD (ASD, X. Zhou). An overview of 4 restraint devices, with their precise advantages and disadvantages, will be presented. The accessible peer-reviewed literature summarized with an important considerations on the mechanism of restraint therapy and how this acquaintance can be accustomed to optimize and improve its effectiveness., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objective: This study aimed at investigating and measuring the positional relationship between the long axis of the mandibular anterior teeth and the alveolar bone using cone beam computed tomography (CBCT) to provide reference data for implant treatment., Methods: From the CBCT image database, 150 cases of radiographic data were selected according to the inclusion criteria and then were divided into six groups: males' mandibular central incisors, males' mandibular lateral incisors, males' mandibular canines, females' mandibular central incisors, females' mandibular lateral incisors, and females' mandibular canines. The angle (β) formed by the long axis of the mandibular anterior teeth and the corresponding alveolar bone was measured and recorded. Based on the long axis of alveolar bone, if the teeth incline to the lingual side, the value of the angle (β) was positive; otherwise, the value was negative. The resultant data were analyzed by SPSS 19.0., Results: The β of the mandibular central incisors presented a mean value of 4.77° (range: -8.17°-16.10°) for male subjects and 5.38° (range: -5.63°-12.93°) for female subjects. The β of the mandibular lateral incisors exhibited a mean value of 6.12° (range: -2.87°-
17.57°) for male subjects and 5.81° (range: -7.70°-15.70°) for female subjects. Finally, the β of the mandibular canines presented a mean value of 5.01° (range: -8.13°-17.67°) for male subjects and 6.21° (range: -7.70°-17.87°) for female subjects. The percentages of the β between -10° and 10° of males' mandibular incisors, mandibular lateral incisors, and mandibular canines were 87.34%, 80.67%, and 88.00%, respectively and those of females were 90.67%, 82.66%, and 82.66%, respectively. Whether male or female, the percentages of the β between -10° and 10° of the mandibular anterior teeth were more than 80%. The β that inclined to the lingual was not more than 20° and to the labial did not exceed 10°., Conclusions: The long axis of the mandibular anterior teeth was almost consistent with the long axis of the alveolar bone. Therefore, the positional relationship could be referred to make reasonable implants treatment plan.

A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P value<0.01) compared to other groups. BNP significantly declines in HF+ASD+SM group animals compared with other treatment groups. Masson's Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: The stigma of major depressive disorder (MDD) is an important public health problem. This study evaluated stigma in MDD patients in China using explanatory model interview catalogue (EMIC) questionnaire and the demographic and clinical symptom factors associated with the stigma of these patients., Methods: A total of 158 MDD patients from domestic 3 mental health centers were surveyed. We used the EMIC questionnaire to assess stigma of these patients, Montgomery and Asberg depression rating scale (MADRS) to assess depressive severity, self-reporting inventory (SCL-90) to assess mental health level, Sheehan disability scale (SDS) to assess social function, and fatigue severity scale (FSS) to assess degree of fatigue., Results: The stigma scores were significantly higher in the 18- to 30-year-old (z = 2.875, P = .024) and 31- to 40-year-old (z = 3.204, P = .008) groups than the 51- to 65-year-old group; in the full-time employment group than the retired group (z = 3.163, P = .016). The stigma scores exhibited significant negative correlation with age (r = -0.169, P = .034) but positive correlations with the scores of MADRS (r = .212, P = .007), total scores (r = .273, P = .001) and subscales of interpersonal sensitivity (r = .233, P = .003), depression (r = .336, P < .001), and anxiety (r = .228, P = .004) of SCL-90, scores of FSS (r = .230, P = .004), and SDS (r = .254, P = .001). Multivariate regression analysis revealed that depression subscale of SCL-90 and FSS were independently correlated with stigma., Conclusion: The age, employment status, fatigue, and depressive severity are closely associated with the perceived stigma of MDD patients and may be important factors considered for stigma interventions of MDD in China., (© 2016 John Wiley & Sons Australia, Ltd.)

In this paper, we propose a simultaneous feature and dictionary learning (SFDL) method for image set-based face recognition, where each training and testing example contains a set of face images, which were captured from different variations of pose, illumination, expression, resolution, and motion. While a variety of feature learning and dictionary learning methods have been proposed in recent years and some of them have been successfully applied to image set-based face recognition, most of them learn features and dictionaries for facial image sets individually, which may not be powerful enough because some discriminative information for dictionary learning may be compromised in the feature learning stage if they are applied sequentially, and vice versa. To address this, we propose a SFDL method to learn discriminative features and dictionaries simultaneously from raw face pixels so that discriminative information from facial image sets can be jointly exploited by a one-stage learning procedure. To better exploit the nonlinearity of face samples from different image sets, we propose a deep SFDL (D-SFDL) method by jointly learning hierarchical non-linear transformations and class-specific dictionaries to further improve the recognition performance. Extensive experimental results on five widely used face data sets clearly shows that our SFDL and D-SFDL achieve very competitive or even better performance with the state-of-the-arts.

Given the prevalence of chronic health conditions, such as diabetes, obesity, epilepsy, and cardiovascular diseases, telemedicine technologies are increasingly adopted to help patients better manage their care and treat these diseases at home. These emerging telemedicine systems have been deployed and tested in a number of different health programs and hospitals. However, due to the lack of dedicated and reliable networking infrastructure, achieving real-time data collection is very challenging task. In this paper, we conduct a comprehensive analysis on the delay issues presented during the use of a store and forward telemonitoring system for congestive heart failure patients in urban Philadelphia. Results from this analysis reveal that 10.3% of the patient measurements experience delays of longer than 12 hours. Delays of up to several days occurred in 15.38% these patients who went on to be hospitalized. These delay issues exposed from urban scale real systems have direct impact on the quality of remote health care, causing late diagnosis and intervention especially when patients are experiencing acute exacerbations. Our investigation results essentially call for regulations on telemedicine systems with an emphasis on their temporal constraints.

Objective: To investigate the predictive value of left ventricular diastolic function on mechanical ventilation weaning in patients with left ventricular ejection fraction (LVEF) > 0.50., Methods: A retrospective case control study was conducted. Sixty-five patients with LVEF > 0.50 undergoing mechanical ventilation for more than 48 hours admitted to surgery intensive care unit (ICU) of China-Japan Friendship Hospital from June 2014 to December 2016 were enrolled. The clinical data and parameters of echocardiography before spontaneous breathing trial (SBT) were collected. The possible relationship between left ventricular diastolic function and the results of weaning was analyzed according to analysis of blood flow filling parameters of mitral valve orifice. According to the grading standard of left ventricular diastolic function, the patients were divided into normal, mild (level 1) and moderate to severe (level 2-3) groups, and the outcomes of weaning were compared among the groups. Then patients were also divided into two groups of weaning successfully and weaning failure, and the clinical data and left ventricular diastolic function parameters of patients were compared between the two groups. The predictive value of left ventricular diastolic function on results of weaning was evaluated with receiver operating characteristic curve (ROC)., Results: Sixty-five patients were enrolled and 28 patients (43.1%) failed weaning, 22 patients failed the first SBT and 6 required reintubation within 48 hours, 31 of the patients presented normal left ventricular diastolic function, 9 of patients presented mild diastolic dysfunction, and 25 of them presented moderate to severe diastolic dysfunction. So with the gradual increase of the severity of diastolic dysfunction, the rate of weaning failure was gradually increased, which was 16.1%, 44.6% and 76.0% respectively (χ 2 = 20.240, P = 0.001). Patients who failed weaning presented evidence of increased left ventricular filling pressures at pre-SBT, by demonstrating decreased deceleration time of E (DTE, s: 180.4±5.1 vs. 196.8±4.0, t = 2.567, P = 0.013), increased left ventricular mitral valve diastolic early and late filling velocity ratio (E/A: 1.47±0.08 vs. 1.14±0.05, t = 3.827, P = 0.000), increased lateral, septal and averaged left ventricular mitral valve diastolic early velocity and maximal velocity of mitral annulus in early diastolic velocity ratio (E/Em: 10.26±0.52 vs. 7.28±0.41, t = 4.535, P = 0.000; 10.08±0.58 vs. 8.16±0.40, t = 2.797, P = 0.007; 10.17±0.48 vs. 7.72±0.35, t = 4.231, P = 0.000), and the rapid shallow breathing index (RSBI) was also increased significantly (61.7±3.6 vs. 50.6±2.7, t = 2.507, P = 0.015). It was shown by ROC curve analysis that the basic left ventricular diastolic function at pre-SBT had the diagnostic performance in predicting the outcome of weaning from mechanical ventilation, especially E/A and lateral E/Em. Pre-SBT values of E/A greater than 1.2 and lateral E/Em greater than 7.9 predicted weaning failure with an area under the ROC curve (AUC), sensitivity, and specificity of 0.81±0.06 and 0.85±0.06, 82.6% and 91.3%, 81.4% and 80.7%, respectively, and the AUC was higher than RSBI (0.70±0.07). The AUC of combination of E/A > 1.2 and lateral E/Em > 7.9 predicting weaning failure was 0.86±0.05 with a sensitivity of 78.3% and a specificity of 93.6%., Conclusions: The results suggest that left ventricular diastolic dysfunction is significantly associated with weaning outcome in critical patients with LVEF > 0.50. The combination of E/A ratio greater than 1.2 and E/Em ratio greater than 7.9 may identify patients at high risk of weaning failure.

Heart failure (HF) is a debilitating disease in which abnormal function of the heart leads to imbalance of blood demand to tissues and organs. The pathogenesis of HF is very complex and various factors can contribute including myocardial infarction, ischemia, hypertension and genetic cardiomyopathies. HF is the leading cause of death and its prevalence is expected to increase in parallel with the population age. Different kind of therapeutic approaches including lifestyle modification, medication and pacemakers are used for HF patients in NYHA I-III functional class. However, for advance stage HF patient's (NYHA IV), ventricle assist devices are clinically use and stem cells are under active investigation. Most of these therapies leads to modest symptoms relief and have no significant role in long-term survival rate. Currently there is no effective treatment for advance HF except heart transplantation, which is still remain clinically insignificant because of donor pool limitation. As HF is a result of multiple etiologies therefore multi-functional therapeutic platform is needed. Exo-organoplasty interventions are studied from almost one century. The major goals of these interventions are to treat various kind of heart disease from outside the heart muscle without having direct contact with blood. Various kind of interventions (devices and techniques) are developed in this arena with the passage of time. The purpose of this review is to describe the theory behind intervention devices, the devices themselves, their clinical results, advantages and limitations. Furthermore, to present a future multi-functional therapeutic platform (ASD) for advance stage HF management., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

In this paper, we present a novel method based on online target-specific metric learning and coherent dynamics estimation for tracklet (track fragment) association by network flow optimization in long-term multi-person tracking. Our proposed framework aims to exploit appearance and motion cues to prevent identity switches during tracking and to recover missed detections. Furthermore, target-specific metrics (appearance cue) and motion dynamics (motion cue) are proposed to be learned and estimated online, i.e., during the tracking process. Our approach is effective even when such cues fail to identify or follow the target due to occlusions or object-to-object interactions. We also propose to learn the weights of these two tracking cues to handle the difficult situations, such as severe occlusions and object-to-object interactions effectively. Our method has been validated on several public datasets and the experimental results show that it outperforms several state-of-the-art tracking methods.

Objective: To assess the clinical significance of computed tomography perfusion (CTP) imaging by evaluating cerebral hemodynamic changes quantitatively and qualitatively both before and after cranioplasty in patients with brain injury., Methods: Sixteen patients with cerebral trauma underwent CTP imaging 2 days before and 10-15 days after cranioplasty. The cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time and time to peak were analysed in both the affected and corresponding contralateral regions, including the basal ganglia, thalamus, cortex and white matter. Quantitative analyses were performed before and after cranioplasty., Results: The CBF in the cortex of the affected side was significantly increased after cranioplasty (p < 0.05), while that in the white matter on the affected side was slightly lower than that on the contralateral side (p < 0.05). The CBV in the corresponding contralateral area of the basal ganglia decreased post-cranioplasty (p < 0.05). No other difference in blood flow parameters was found between the two sides before or after cranioplasty., Conclusion: CTP imaging can accurately reflect changes in cerebral hemodynamics before and after cranioplasty in patients with trauma. Cranioplasty can significantly improve CBF in the cortex on the affected side for a short time (10-15 days) to meet the prevailing metabolic demand.

Objective: This study aims to analyze the angulation of the maxillary anterior teeth relative to the alveolus to provide reference data for clinicians on the best conditions for implant placement in the esthetic zone., Methods: Numerous cone beam computed tomography (CBCT) images were reviewed and screened. A total of 150 maxillary images were selected by strict adherence to the defined inclusive criteria, with 75 images each from male and female patients (between the ages of 19 and 48 years at the time of CBCT scan). The maxillary anterior teeth were gathered into the following three groups for males and females: upper canines, upper lateral incisors, and upper central incisors. Then, the long axis of each qualified tooth and its corresponding alveolar process were drawn, and the angles formed by these structures were measured. The resultant data were analyzed by SPSS 19.0., Results: The long axis of the maxillary anterior teeth all inclined to the palatal side of the alveolar process. The internal angle (α) formed by the long axis of the maxillary central incisors and the long axis of the alveolar bone presented a mean value of 16.22° (range: 2.50°-28.80°) for male subjects and 15.20° (range: 2.20°-27.20°) for female subjects. The internal angle (α) of the maxillary lateral incisors exhibited a mean value of 17.50° (range: 3.80°-29.50°) for male subjects and 15.99° (range: 4.10°-33.30°) for female subjects. Finally, the internal angle (α) of the maxillary canines presented a mean value of 16.27° (range: 1.00°-31.50°) for male subjects and 15.01° (range: 3.50°-27.40°) for female subjects., Conclusions: The long axis of the maxillary anterior teeth all inclined to the palatal side of the alveolar process. For implant placement, careful preoperative analysis and evaluation with CBCT may be beneficial for avoiding the risk factors and achieving
a high probability of success in the esthetic region.

Nucleoside or nucleotide inhibitors are a highly successful class of antivirals due to selectivity, potency, broad coverage, and high barrier to resistance. Nucleosides are the backbone of combination treatments for HIV, hepatitis B virus, and, since the FDA approval of sofosbuvir in 2013, also for hepatitis C virus (HCV). However, many promising nucleotide inhibitors have advanced to clinical trials only to be terminated due to unexpected toxicity. Here we describe the in vitro pharmacology of compound 1, a monophosphate prodrug of a 2'-ethynyluridine developed for the treatment of HCV. Compound 1 inhibits multiple HCV genotypes in vitro (50% effective concentration [EC 50 ], 0.05 to 0.1 μM) with a selectivity index of >300 (50% cytotoxic concentration [CC 50 ], 30 μM in MT-4 cells). The active triphosphate metabolite of compound 1, compound 2, does not inhibit human α, β, or γ DNA polymerases but was a substrate for incorporation by the human mitochondrial RNA polymerase (POLRMT). In dog, the oral administration of compound 1 resulted in elevated serum liver enzymes and microscopic changes in the liver. Transmission electron microscopy showed significant mitochondrial swelling and lipid accumulation in hepatocytes. Gene expression analysis revealed dose-proportional gene signature changes linked to loss of hepatic function and increased mitochondrial dysfunction. The potential of in vivo toxicity through mitochondrial polymerase incorporation by nucleoside analogs has been previously shown. This study shows that even moderate levels of nucleotide analog incorporation by POLRMT increase the risk of in vivo mitochondrial dysfunction. Based on these results, further development of compound 1 as an anti-HCV compound was terminated., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell (CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer (liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.

Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling, targeting IκB kinase-α (IKKα) and IKKβ kinases of macrophages and influencing the expressions of NF-κB downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages. In vivo study with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate from Anoectochilus roxburghi to treat gouty arthritis clinically.

Matching people across multiple camera views known as person reidentification is a challenging problem due to the change in visual appearance caused by varying lighting conditions. The perceived color of the subject appears to be different under different illuminations. Previous works use color as it is or address these challenges by designing color spaces focusing on a specific cue. In this paper, we propose an approach for learning color patterns from pixels sampled from images across two camera views. The intuition behind this work is that, even though varying lighting conditions across views affect the pixel values of the same color, the final representation of a particular color should be stable and invariant to these variations, i.e., they should be encoded with the same values. We model color feature generation as a learning problem by jointly learning a linear transformation and a dictionary to encode pixel values. We also analyze different photometric invariant color spaces as well as popular color constancy algorithm for person reidentification. Using color as the only cue, we compare our approach with all the photometric invariant color spaces and show superior performance over all of them. Combining with other learned low-level and high-level features, we obtain promising results in VIPeR, Person Re-ID 2011, and CAVIAR4REID data sets.

Alcoholic liver disease (ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis (steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage.

Testicular seminoma is a common malignancy, accounting for 35-50% of testicular tumors. Comprehensive therapies lead to good curative efficacy. However, the factors that affect prognosis remain to be elucidated. The aim of the present study was to analyze the 3-, 5- and 10-year survival rate of patients with testicular seminoma as well as the associated factors of prognosis. The clinical data from 58 patients diagnosed with testicular seminoma were collected betweeen January 1999 and January 2014. The survival rate for this group was evaluated using the Kaplan-Meier method. Associated factors of prognosis were analyzed using the log-rank test. The results showed that approximately 62.1% of the cases were in the 30- to 50-year age group. From this age group, 94.8% of patients survived for 3 years, 86.2% for 5 years and 70.7% for 10 years. A significant difference was identified for the different clinical stages, pathological types and postoperative treatment in the 3-, 5- and 10-year survival rates (P<0.05). In conclusion, the clinical stages, pathological types and postoperative treatments significantly affect the prognosis of testicular seminoma. Selection of an appropriate method of treatment including the clinical stages and histological types, is the key element in testicular seminoma therapy.

Human hepatocellular carcinoma (HCC) heavily endangers human heath worldwide. HCC is one of most frequent cancers in China because patients with liver disease, such as chronic hepatitis, have the highest cancer susceptibility. Traditional therapeutic approaches have limited efficacy in advanced liver cancer, and novel strategies are urgently needed to improve the limited treatment options for HCC. This review summarizes the basic knowledge, current advances, and future challenges and prospects of adeno-associated virus (AAV) and adenoviruses as vectors for gene therapy of HCC. This paper also reviews the clinical trials of gene therapy using adenovirus vectors, immunotherapy, toxicity and immunological barriers for AAV and adenoviruses, and proposes several alternative strategies to overcome the therapeutic barriers to using AAV and adenoviruses as vectors.

Aim: To describe the application of complete robotic gastrectomy with transvaginal specimen extraction (TVSE) for gastric cancer patients., Methods: Between July and November 2014, eight female patients who were diagnosed with gastric adenocarcinoma underwent a TVSE following a full robot-sewn gastrectomy. According to the tumor location, the patients were allocated to two different groups; two patients received robotic total gastrectomy with TVSE and the other six received robotic distal gastrectomy with TVSE., Results: Surgical procedures were successfully performed in all eight cases without conversion. The mean age was 55.3 (range, 42-69) years, and the mean body mass index was 23.2 (range, 21.6-26.0) kg/m(2). The mean total operative time and blood loss were 224 (range, 200-298) min and 62.5 (range, 50-150) mL, respectively. The mean postoperative hospital stay was 3.6 (range, 3-5) d. The mean number of lymph nodes resected was 23.6 (range, 17-27). None was readmitted within 30 d of postoperation. During the follow-up, no stricture developed nor was any anastomotic leakage detected., Conclusion: It is possible to perform a TVSE following a full robot-sewn gastrectomy with standard D2 lymph node resection for female gastric cancer patients.

Aim: To evaluate the long-term outcomes of Oddi sphincter preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS) and risk factors for recurrence in hepatolithiasis., Methods: From March 1993 to December 2012, 202 consecutive patients with hepatolithiasis underwent OSPCHS at our department. The Oddi sphincter preserved procedure consisted of common hepatic duct exploration, stone extraction, hilar bile duct plasty, establishment of subcutaneous stoma to the bile duct. Patients with recurrent stones can undergo stone extraction and/or biliary drainage via the subcutaneous stoma which can be incised under local anesthesia. The long-term results were reviewed. Cox regression model was employed to analyze the risk factors for stone recurrence., Results: Ninety-seven (48.0%) OSPCHS patients underwent hepatic resection concomitantly. The rate of surgical complications was 10.4%. There was no perioperative death. The immediate stone clearance rate was 72.8%. Postoperative cholangioscopic lithotomy raised the clearance rate to 97.0%. With a median follow-up period of 78.5 mo (range: 2-233 mo), 24.8% of patients had recurrent stones, 2.5% had late development of cholangiocarcinoma, and the mortality rate was 5.4%. Removal of recurrent stones and/or drainage of inflammatory bile via subcutaneous stoma were conducted in 44 (21.8%) patients. The clearance rate of recurrent stones was 84.0% after subsequent choledochoscopic lithotripsy via subcutaneous stoma. Cox regression analysis showed that residual stone was an independent prognostic factor for stone recurrence., Conclusion: In selected patients with hepatolithiasis, OSPCHS achieves excellent long-term outcomes, and residual stone is an independent prognostic factor for stone recurrence.

Aim: To explore the effect of the histone deacetylase inhibitor givinostat on proteins related to regulation of hepatic stellate cell proliferation., Methods: The cell counting kit-8 assay and flow cytometry were used to observe changes in proliferation, apoptosis, and cell cycle in hepatic stellate cells treated with givinostat. Western blot was used to observe expression changes in p21, p57, CDK4, CDK6, cyclinD1, caspase-3, and caspase-9 in hepatic stellate cells exposed to givinostat. The scratch assay was used to analyze the effect of givinostat on cell migration. Effects of givinostat on the reactive oxygen species profile, mitochondrial membrane potential, and mitochondrial permeability transition pore opening in JS-1 cells were observed by laser confocal microscopy., Results: Givinostat significantly inhibited JS-1 cell proliferation and promoted cell apoptosis, leading to cell cycle arrest in G0/G1 phases. Treatment with givinostat downregulated protein expression of CDK4, CDK6, and cyclin D1, whereas expression of p21 and p57 was significantly increased. The givinostat-induced apoptosis of hepatic stellate cells was mainly mediated through p38 and extracellular signal-regulated kinase 1/2. Givinostat treatment increased intracellular reactive oxygen species production, decreased mitochondrial membrane potential, and promoted mitochondrial permeability transition pore opening. Acetylation of superoxide dismutase (acetyl K68) and nuclear factor-κB p65 (acetyl K310) was upregulated, while there was no change in protein expression. Moreover, the notable beneficial effect of givinostat on liver fibrosis was also confirmed in the mouse models., Conclusion: Givinostat has antifibrotic activities via regulating the acetylation of nuclear factor-κB and superoxide dismutase 2, thus inhibiting hepatic stellate cell proliferation and inducing apoptosis.

Aim: To investigate the role of signal transduction and activation of transcription 4 (STAT4) in the development and progression of human hepatocellular carcinoma (HCC)., Methods: Recent genetic investigations have identified that a genetic variant of STAT4 is associated with hepatitis B virus (HBV)-related HCC. The level of STAT4 in 90 HCC patients was examined via Western blot and immunohistochemical analyses. The correlation between STAT4 expression and the clinicopathological characteristics of the patients was analyzed. The level of STAT4 expression in the HCC liver tissues was significantly lower than that in the non-HCC liver tissues and correlated with tumor size, histological grade of HCC and serum hepatitis B surface antigen level in HCC patients. The data were statistically analyzed using SPSS. Furthermore, siRNA oligos targeting STAT4 were employed to investigate the influence of STAT4 RNA interference on HCC cell physiology. Based on Cell Counting Kit-8 and flow cytometric assays, we found that depletion of STAT4 expression significantly enhanced the proliferation of L02 cells., Results: STAT4 protein expression was significantly lower in HCC tissues than in normal liver tissues. Immunohistochemistry followed by statistical analysis revealed that the expression of STAT4 negatively correlated with Ki67 expression (r = 0.851; P < 0.05) and positively correlated with maximal tumor size (P < 0.05), HBV (P = 0.012) and histological grade (P < 0.05). Kaplan-Meier analysis revealed significant differences in the survival curves between HCC patients expressing low and high levels of STAT4 and Ki67 (P < 0.05). Based on a multivariate Cox proportional hazard model, STAT4 expression was an independent prognostic indicator for HCC patients who underwent curative resection. In vitro, following the release of L02 cell lines from serum starvation, the expression of STAT4 was downregulated, and transfection of L02 cells with siRNA targeting STAT4 inhibited cell proliferation., Conclusion: Our data indicate that STAT4 may inhibit HCC development by modulating HCC cell proliferation.

In this paper, we propose an approach to learn hierarchical features for visual object tracking. First, we offline learn features robust to diverse motion patterns from auxiliary video sequences. The hierarchical features are learned via a two-layer convolutional neural network. Embedding the temporal slowness constraint in the stacked architecture makes the learned features robust to complicated motion transformations, which is important for visual object tracking. Then, given a target video sequence, we propose a domain adaptation module to online adapt the pre-learned features according to the specific target object. The adaptation is conducted in both layers of the deep feature learning module so as to include appearance information of the specific target object. As a result, the learned hierarchical features can be robust to both complicated motion transformations and appearance changes of target objects. We integrate our feature learning algorithm into three tracking methods. Experimental results demonstrate that significant improvement can be achieved using our learned hierarchical features, especially on video sequences with complicated motion transformations.

Aim: To investigate the relationship between cholecystectomy and fatty liver disease (FLD) in a Chinese population., Methods: A total of 32428 subjects who had voluntarily undergone annual health checkups in the Second Affiliated Hospital of Nanjing Medical University from January 2011 to May 2013 were included in this study. Basic data collection, physical examination, laboratory examination, and abdominal ultrasound examination were performed., Results: Subjects undergoing cholecystectomy were associated with greater age, female sex, higher body mass index, and higher levels of systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglycerides. However, no significant differences were found in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, albumin, and serum uric acid. The overall prevalence of FLD diagnosed by ultrasonography was high at 38.4%. The prevalence of FLD was significantly higher for subjects who had undergone cholecystectomy (46.9%) than those who had not undergone cholecystectomy (38.1%; χ(2) test, P < 0.001). Cholecystectomy was positively associated with FLD (OR = 1.433, 95%CI: 1.259-1.631). However, after adjusting for possible factors associated with FLD, multivariate regression analysis showed that the association between cholecystectomy and FLD was not statistically significant (OR = 1.096; 95%CI: 0.939-1.279)., Conclusion: According to our study results, cholecystectomy may not be a significant risk factor for FLD.

Objective: To evaluate the influence of polymorphisms in nucleotide excision repair (NER) and homologous recombination repair (HRR) pathways on the development of osteosarcoma patients., Methods: Genotypes of ERCC1 rs11615 and rs3212986, ERCC2 rs1799793 and rs13181, NBN rs709816 and rs1805794, RAD51 rs1801320, rs1801321 and rs12593359, and XRCC3 rs861539 were conducted by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) assay., Results: Total 148 osteosarcoma patients and 296 control subjects were collected from Taizhou First People's Hospital. Conditional logistic regression analyses found that individuals carrying with GA+AA genotype of ERCC2 rs1799793 and GC+CC genotype of NBN rs1805794 were significantly associated with increased risk of osteosarcoma, and the ORs(95%CI) were 1.58(1.03-2.41) and 2.66(1.73-4.08), respectively. We found that GA+AA genotype of ERCC2 rs1799793 or GC+CC genotype of NBN rs1805794 were associated with an increased risk of osteosarcoma in females, with ORs(95%CI) of 2.42(1.20-4.87) and 2.01(1.07-4.23), respectively., Conclusion: Our results suggest that ERCC2 rs1799793 and NBN rs1805794 polymorphisms were associated with an increased risk for osteosarcoma, which suggests that NER and HRR pathways modulate the risk of developing osteosarcoma.

Aim: To compare the effects and postoperative complications between tissue selecting therapy stapler (TST) and Milligan-Morgan hemorrhoidectomy (M-M)., Methods: Four hundred and eighty patients with severe prolapsing hemorrhoids, who were admitted to the Shenyang Coloproctology Hospital between 2009 and 2012, were randomly divided into observation (n=240) and control (n=240) groups. Hemorrhoidectomies were performed with TST in the observation group and with the M-M technique in the control group. The therapeutic effects, operation security, and postoperative complications in the two groups were compared. The immediate and long-term complications were assessed according to corresponding criteria. Pain was assessed on a visual analogue scale. The efficacy was assessed by specialized criteria. The follow-up was conducted one year after the operation., Results: The total effective rates of the observation and control groups were 99.5% (217/218) and 98.6% (218/221) respectively; the difference was not statistically significant (P=0.322). Their were significant differences between observation and control groups in intraoperative blood loss (5.07±1.14 vs 2.45±0.57, P=0.000), pain (12 h after the surgery: 5.08±1.62 vs 7.19±2.01, P=0.000; at first dressing change: 2.64±0.87 vs 4.34±1.15, P=0.000; first defecation: 3.91±1.47 vs 5.63±1.98, P=0.001), urine retention (n=22 vs n=47, P=0.001), anal pendant expansion after the surgery (2.35±0.56 vs 5.16±1.42, P=0.000), operation time (18.3±5.6 min vs 29.5±8.2 min, P=0.000), and the length of hospital stay (5.3±0.6 d vs 11.4±1.8 d, P=0.000). Moreover TST showed significant reductions compared to M-M in the rates of long-term complications such as fecal incontinence (n=3 vs n=16, P=0.003), difficult bowel movement (n=1 vs n=9, P=0.011), intractable pain (n=2 vs n=12, P=0.007), and anal discharge (n=3 vs n=23, P=0.000)., Conclusion: TST for severe prolapsing hemorrhoids is a satisfactory technique for more rapid recovery, lower complication rates, and higher operation security.

Aim: To investigate the impact of enteral nutrition (EN) on the body composition and metabolism in patients with Crohn's disease (CD)., Methods: Sixty-one patients diagnosed with CD were enrolled in this study. They were given only EN (enteral nutritional suspension, TPF, non-elemental diet) support for 4 wk, without any treatment with corticosteroids, immunosuppressive drugs, infliximab or by surgical operation. Body composition statistics such as weight, body mass index, skeletal muscle mass (SMM), fat mass, protein mass and inflammation indexes such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and CD activity index (CDAI) were recorded before and after EN support., Results: The 61 patients were divided into three groups according to CDAI before and after EN support: A (active phase into remission via EN, n=21), B (remained in active phase before and after EN, n=19) and C (in remission before and after EN, n=21). Patients in group A had a significant increase in SMM (22.11±4.77 kg vs 23.23±4.49 kg, P=0.044), protein mass (8.01±1.57 kg vs 8.44±1.45 kg, P=0.019) and decrease in resting energy expenditure (REE) per kilogram (27.42±5.01 kcal/kg per day vs 22.62±5.45 kcal/kg per day, P<0.05). There was no significant difference between predicted and measured REE in active CD patients according to the Harris-Benedict equation. There was no linear correlation between the measured REE and CRP, ESR or CDAI in active CD patients., Conclusion: EN could decrease the hypermetabolism in active CD patients by reducing the inflammatory response.

Objective: : Several previous studies have reported the role variant of ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms in the risk of glioma, but the results of these studies are inconsistent. Therefore, we aimed to conduct a meta-analysis to investigate the role of ERCC1 rs3212986 and ERCC2 rs13181 on the risk of glioma., Methods: A comprehensive research was conducted through the databases of Pubmed, EMBASE and the China National Knowledge Infrastructure (CNKI) platforms until June 1, 2014, including 14 eligible case-control studies., Results: Our meta-analysis found that ERCC1 rs3212986 AA genotype was significantly associated with increased risk of glioma compared with CC genotype, and the pooled OR (95%CI) was 1.29(1.07-1.55). By subgroup analysis, ERCC1 rs3212986 AA genotype was found to be significantly correlated with increased glioma risk in Chinese population (OR=1.37, 95%CI=1.07, 1.55), Similarly, we found that ERCC2 rs13181 GT and TT genotypes were significantly associated with increased risk of glioma in Chinese population, with ORs(95%CI) of 1.47(1.17-1.85) and 1.50(1.02-2.22). But ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms had no significant association with glioma risk in Caucasian populations. By begg's funnel plot, we found that no publication bias was existed in this meta-analysis., Conclusion: Our meta-analysis suggested that ERCC1 rs3212986 and ERCC2 rs13181 polymorphism play an important risk factor for brain tumor development in Chinese population, but no association in Caucasian populations.

Aim: To investigate the feasibility, efficacy and safety of laparoscopic hepaticoplasty using gallbladder as subcutaneous tunnel and sphincter-of-Oddi preservation for hepatolithiasis., Methods: From January 2010 to July 2013, six patients with hepatolithiasis were treated at our institution. All the patients underwent laparoscopic surgery. The procedures included common hepatic duct exploration, stone clearance by fiberoptic choledochoscopy, hilar bile duct hepaticoplasty with preservation of the sphincter of Oddi, anastomosis between the hilar bile duct and neck of the gallbladder, and establishment of a subcutaneous tunnel with the gallbladder. Two patients underwent left lateral hepatectomy simultaneously. Clinical data including operation time, intraoperative blood loss, operative morbidity, hospital mortality, stone clearance, and recurrence rate were analyzed., Results: All patients successfully completed laparoscopic surgery. The mean length of hospital stay was 4.5 ± 0.9 d (range: 3-6 d). The mean blood loss of the hepatectomy was 450 mL (range: 200-700 mL), and the blood loss of the other four was 137 ± 151 mL (range: 50-400 mL). The mean operative time was 318 ± 68 min (range: 236-450 min). The operative morbidity and hospital mortality were zero. The immediate stone clearance rate was 100%. All patients were followed up for an average of 17 mo (range: 7-36 mo). One of the six patients had abdominal mass with pain, and subcutaneous tunnel cholangiography showed severe gallbladder-biliary anastomotic stricture at 4 mo postoperatively. There was no stone recurrence and no cholangitis during follow-up., Conclusion: Laparoscopic hepaticoplasty using gallbladder with a subcutaneous tunnel and preserving the sphincter of Oddi is feasible, safe and effective for hepatholithiasis.