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This paper aims at intensifying the synthesis process of solketal by the reactive dividing wall column (RDWC) through experiments and simulation optimization and proposes a high-efficiency producti...

Apart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallbladder cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin (SCEL) in GBC cell proliferation and the development of venous thromboembolism. The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methods. SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis, thus serving as a potential therapeutic target.

The purpose is to optimize the optical fiber Fabry–Perot (F-P) sensor’s performances to provide a realistic basis for the optical fiber’s development. First, the classification of the optical fiber F-P sensors is summarized. The optical fiber F-P sensors’ fundamental principles are analyzed, focusing on the phase demodulation method that converts the optical fiber F-P sensing system’s input light source into a broadband light source. The broadband light source’s lightwave changes are analyzed, and the Fourier transform method and the fringe counting method are proposed to optimize the phase demodulation method’s function and analyze the light source’s nonlinear dynamic characteristics. According to the proposed demodulation method, the optical fiber F-P sensor with a cavity length change of [Formula: see text][Formula: see text][Formula: see text]m is simulated, and the cavity length selected for the simulation spectrum is the change range’s center value, 185[Formula: see text]um. The wavelength division multiplexer (WDM) decomposes the two optical signals, and an equation directly calculates the wavelength value orthogonal to its phase. The results show that the light intensity’s initial value of the actual spectrum is 0.04, and that of the standard function is 0.06. The light intensities for the maximum peak values are the same, 0.12, with the wavelength in [Formula: see text]–[Formula: see text][Formula: see text]m. When the wavelength exceeds [Formula: see text][Formula: see text]m before the next peak, the light intensity difference between them is large. The two orthogonal optical signals’ peaks change between the cavity length 0.18[Formula: see text]nm and 0.19[Formula: see text]nm after the wavelength selected, and the two signals’ peak values are orthogonal with the cavity length changes. The two signals’ initial and end peak values are different. The curve obtained by the two signals division calculation shows a tangent trend with the highest peak value of 87 and the lowest of [Formula: see text]. The peak curve changes obtained by the two signals’ arctangent calculation are in an orthogonal state, with the maximum peak value of 1.3 and the minimum of [Formula: see text]. The reflected light peak value changes of the optical fiber F-P sensor are in an orthogonal state, with the highest value of [Formula: see text] and the lowest [Formula: see text], and the adjacent peak changes in the wavelengths of 1500–1580 are the same. The curve’s fitting linearity is 1, and the linearity in the dynamic demodulation is 0.9776. The sampling frequency in the phase demodulation is [Formula: see text][Formula: see text]Hz, and the sampling frequency in the dynamic demodulation is [Formula: see text][Formula: see text]Hz, showing that upgrading the interface can increase the dynamic sampling frequency continuously to improve the device performance.

In recent years, convolutional neural networks (CNNs) have become the predominant method for content-based aerial image retrieval (CBAIR) and aerial scene classification (ASC) due to their overwhelming performance advantages. However, existing CNN-based models have the following shortcomings: first, they do not deal with large intraclass variations, thereby overlooking the possibility of fine-grained retrieval and classification; second, all similarity learning methods for CBAIR consider similarity between two images as a constant, neglecting the fact that image similarity is uncertain in nature; third, similarity learning is separated from ASC, ignoring the advantages of joint optimization. To address these issues, we propose a novel metric learning method called center-metric learning, and couple it with a new kind of loss called positive-negative center loss, which, with the help of several “experts,” enables CNNs to cope successfully with within-class variations. Besides, we propose similarity distribution learning, making the first attempt to embed uncertainty regarding similarity into the training process. The resulting fine-grained similarity predictions can further strengthen CNNs’ fine discrimination ability. Furthermore, three tasks, that is, center-metric learning, similarity distribution learning, and ASC, are incorporated into one CNN, benefitting from one another and leading to a better generalization capability. Just like an eagle, our model is able to discriminate subtle differences among aerial images, hence the name “eagle-eyed multitask CNN.” We carry out extensive experiments over four publicly available aerial image sets and achieve a performance better than all existing methods.

Gallbladder carcinoma (GBC) is a vicious and invasive disease. The major challenge in the clinical treatment of GBC is the lack of a suitable prognosis method. Chemokine receptors such as CXCR3, CXCR4 and CXCR7 play vital roles in the process of tumour progression and metastasis. Their expression levels and distribution are proven to be indicative of the progression of GBC, but are hard to be decoded by conventional pathological methods, and therefore, not commonly used in the prognosis of GBC. In this study, we developed a computer‐aided image analysis method, which we used to quantitatively measure the expression levels of CXCR3, CXCR4 and CXCR7 in the nuclei and cytoplasm of glandular and interstitial cells from a cohort of 55 GBC patients. We found that CXCR3, CXCR4 and CXCR7 expressions are associated with the clinicopathological variables of GBC. Cytoplasmic CXCR3, nuclear CXCR7 and cytoplasmic CXCR7 were significant predictive factors of histology invasion, whereas cytoplasmic CXCR4 and nuclear CXCR4 were significantly correlated with T and N stage and were associated with the overall survival and disease‐free survival. These results suggest that the quantification and localisation of CXCR3, CXCR4 and CXCR7 expressions in different cell types should be considered using computer‐aided assessment to improve the accuracy of prognosis in GBC.

Background Liver cancer remains the leading cause of cancer death globally, and the treatment strategies are distinct for each type of malignant hepatic tumors. However, the differential diagnosis before surgery is challenging and subjective. This study aims to build an automatic diagnostic model for differentiating malignant hepatic tumors based on patients’ multimodal medical data including multi-phase contrast-enhanced computed tomography and clinical features. Methods Our study consisted of 723 patients from two centers, who were pathologically diagnosed with HCC, ICC or metastatic liver cancer. The training set and the test set consisted of 499 and 113 patients from center 1, respectively. The external test set consisted of 111 patients from center 2. We proposed a deep learning model with the modular design of SpatialExtractor-TemporalEncoder-Integration-Classifier (STIC), which take the advantage of deep CNN and gated RNN to effectively extract and integrate the diagnosis-related radiological and clinical features of patients. The code is publicly available at https://github.com/ruitian-olivia/STIC-model. Results The STIC model achieved an accuracy of 86.2% and AUC of 0.893 for classifying HCC and ICC on the test set. When extended to differential diagnosis of malignant hepatic tumors, the STIC model achieved an accuracy of 72.6% on the test set, comparable with the diagnostic level of doctors’ consensus (70.8%). With the assistance of the STIC model, doctors achieved better performance than doctors’ consensus diagnosis, with an increase of 8.3% in accuracy and 26.9% in sensitivity for ICC diagnosis on average. On the external test set from center 2, the STIC model achieved an accuracy of 82.9%, which verify the model’s generalization ability. Conclusions We incorporated deep CNN and gated RNN in the STIC model design for differentiating malignant hepatic tumors based on multi-phase CECT and clinical features. Our model can assist doctors to achieve better diagnostic performance, which is expected to serve as an AI assistance system and promote the precise treatment of liver cancer.

BACKGROUND Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.

In multiclass classification, convolutional neural network (CNN) is generally coupled with the cross-entropy (CE) loss, which only penalizes the predicted probability corresponding to a ground truth class and ignores the interclass relationship. We argue that CNN can be improved by using a better loss function. On the other hand, the Wasserstein distance (WD) is a well-known metric used to measure the distance between two distributions. Directly solving the WD problem requires a prohibitively large amount of computation time, whereas the cheaper iterative algorithms have a variety of shortcomings such as computational instability and difficulty in selecting parameters. In this paper, we address these issues by giving an analytical solution to the WD problem—for the first time, we find that for two distributions in hierarchically organized data space, WD has a closed-form solution, which we call “hierarchical WD (HWD).” We use this theory to construct novel loss functions that overcome the shortcomings of CE loss. To this end, multi-CNN information fusion that provides the basis for building category hierarchies is carried out first. Then, the semantic relationship among classes is modeled as a binary tree. Then, CNN coupled with an HWD-based loss, i.e., hierarchical Wasserstein CNN (HW-CNN), is trained to learn deep features. In this way, prior knowledge about the interclass relationship is embedded into HW-CNN, and information from several CNNs provides guidance in the process of training individual HW-CNNs. We conducted extensive experiments over two publicly available remote sensing data sets and achieved a state-of-the-art performance in scene classification tasks.

The traditional convolutional neural networks (CNNs) coupled with cross-entropy loss ignore interclass relationship, and hence output unreasonable predictions from a holistic perspective. We address this issue by integrating CNNs with Wasserstein distance (WD): first, we find that the classical WD problem has an analytical solution in the case of multiclass classification; second, by leveraging multiple pretrained CNNs to extract multiscale convolutional features and encoding the features via the improved Fisher kernel, we propose a novel method for computing the ground distance matrix, which characterizes the affinities between classes and is also a key component of the WD problem; third, we use the analytical solution to construct new losses for CNNs. Our proposed model is applied to scene classification and leads to a higher performance than other methods.

IntroductionGallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population.Methods and analysisThe Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers.Ethics and disseminationThe protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019–085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences.Trial registration numberNCT04140552, Pre-results.

Background Gemcitabine plus platinum as the first-line chemotherapy for cholangiocarcinoma (CCA) has limited efficacy. The aim of this study was to evaluate the effectiveness of modified FOLFIRINOX (mFOLFIRINOX) compared to that of gemcitabine plus oxaliplatin (Gemox) for patients with locally advanced or metastatic CCA. Methods From January 2016 to December 2019, consecutive patients who were diagnosed with locally advanced or metastatic CCA were treated with either mFOLFIRINOX or Gemox as a first-line chemotherapy. The main endpoint was Progression free survival (PFS). The second endpoints were Overall survival (OS), Disease control rate (DCR) and incidence of severe toxicity (grade 3–4). Tumors were evaluated at baseline and thence every 4–6 weeks. The study was designed and carried out in accordance with the principles of the declaration of Helsinki, approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHEC-D-2020-154) and registered with ClinicalTrials.gov, number NCT04305288 (registration date: 12/03/2020). Results Of 49 patients in this study, 27 were in the FOLFIRINOX regimen group and 22 in the Gemox regimen group. There were no significant differences between groups in baseline characteristics. The DCR was 77.8% in the mFOLFIRINOX group and 63.5% in the Gemox group. The corresponding median PFS was 9.9 months (95% confidence interval [CI], 7.3–12.4) in the mFOLFIRINOX group versus 6.4 months (95% CI,3.6–9.2, p = 0.040) in the Gemox group. The corresponding median OS was 15.7 months (95% CI, 12.5–19.0) versus 12.0 months (95% CI, 9.3–14.8, p = 0.099). Significantly more grade 3–4 vomiting occurred in the mFOLFIRINOX than the Gemox groups (7 (25.9%) vs 1 (4.5%), p = 0.044). Conclusions First-line mFOLFIRINOX offered more promising results in patients with advanced or metastatic CCA.

Gallbladder cancer (GBC) is rare, but is the most malignant type of biliary tract tumor. Unfortunately, only a small population of cancer patients is acceptable for the surgical resection, the current effective regimen; thus, the high mortality rate has been static for decades. To substantially circumvent the stagnant scenario, a number of therapeutic approaches owing to the creation of advanced technologic measures (e.g., next-generation sequencing, transcriptomics, proteomics) have been intensively innovated, which include targeted therapy, immunotherapy, and nanoparticle-based delivery systems. In the current review, we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC. Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease, ultimately improving the efficacy of treatment.

Aiming at the problems of the existing quasi-distributed optical fiber sensing measurement technology, such as complexity, low accuracy and slow response time, a quasi-distributed optical fiber water leakage monitoring system with high real-time performance and lower cost is designed; the system is mainly composed of sensitive detection. It is composed of needle, low light detection unit, main control unit and data transmission unit. The lateral coupling effect forms a series of sensing probes after the LED light source is scanned. Light enters the polymer fiber through the lateral coupling structure. When the medium between the LED and the coupling structure changes, the coupling light intensity increases, and the output light intensity at both ends of the fiber increases accordingly, so the liquid leakage event can be converted into a coupling medium change To measure and cooperate with several other modules to complete the construction of a water leakage monitoring system; the results show that the designed fiber-optic water leakage monitoring system has the ability to detect and locate water leakage signals, and the positioning accuracy is less than or equal to 10 cm. Basically realize the functions of liquid leakage detection and leakage point positioning, which conforms to the characteristics of quasi-distributed measurement.

Three-dimensional (3D) visualization involves feature extraction and 3D reconstruction of CT images using a computer processing technology. It is a tool for displaying, describing, and interpreting 3D anatomy and morphological features of organs, thus providing intuitive, stereoscopic, and accurate methods for clinical decision-making. It has played an increasingly significant role in the diagnosis and management of liver diseases. Over the last decade, it has been proven safe and effective to use 3D simulation software for pre-hepatectomy assessment, virtual hepatectomy, and measurement of liver volumes in blood flow areas of the portal vein; meanwhile, the use of 3D models in combination with hydrodynamic analysis has become a novel non-invasive method for diagnosis and detection of portal hypertension. We herein describe the progress of research on 3D visualization, its workflow, current situation, challenges, opportunities, and its capacity to improve clinical decision-making, emphasizing its utility for patients with liver diseases. Current advances in modern imaging technologies have promised a further increase in diagnostic efficacy of liver diseases. For example, complex internal anatomy of the liver and detailed morphological features of liver lesions can be reflected from CT-based 3D models. A meta-analysis reported that the application of 3D visualization technology in the diagnosis and management of primary hepatocellular carcinoma has significant or extremely significant differences over the control group in terms of intraoperative blood loss, postoperative complications, recovery of postoperative liver function, operation time, hospitalization time, and tumor recurrence on short-term follow-up. However, the acquisition of high-quality CT images and the use of these images for 3D visualization processing lack a unified standard, quality control system, and homogeneity, which might hinder the evaluation of application efficacy in different clinical centers, causing enormous inconvenience to clinical practice and scientific research. Therefore, rigorous operating guidelines and quality control systems need to be established for 3D visualization of liver to develop it to become a mature technology. Herein, we provide recommendations for the research on diagnosis and management of 3D visualization in liver diseases to meet this urgent need in this research field.

In convolutional neural networks (CNNs), higher layer information is more abstract and more task specific, so people usually concern themselves with fully connected (FC) layer features, believing that lower layer features are less discriminative. However, a few researchers showed that the lower layers also provide very rich and powerful information for image representation. In view of these study findings, in this letter, we attempt to adaptively and explicitly combine the activations from intermediate and FC layers to generate a new CNN with directed acyclic graph topology, which is called the converted CNN. After that, two converted CNNs are integrated together to further improve the classification performance. We validate our proposed two-stage deep feature fusion model over two publicly available remote sensing data sets, and achieve a state-of-the-art performance in scene classification tasks.

// Peng-Yuan Zhuang 1, * , Ke-Wei Zhang 1, * , Jian-Dong Wang 1 , Xue-Ping Zhou 1 , Ying-Bin Liu 1 , Zhi-Wei Quan 1 and Jun Shen 1 1 Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jun Shen, email: shenjun@xinhuamed.com.cn Keywords: hepatocellular carcinoma, IL-6, TALEN Received: June 05, 2017 Accepted: July 26, 2017 Published: September 15, 2017 ABSTRACT Purpose: To determine the exact effect of Interleukin-6 (IL-6) on tumor cell proliferation, apoptosis, invasion, and anti-cancer therapy in hepatocellular carcinoma (HCC). Experimental Design: IL-6 was disrupted by transcription activator-like effector nucleases (TALEN) in HCCLM3 cells, and was used to evaluate the role of IL-6 on tumor cell proliferation, apoptosis, invasion and key signaling pathways involved in sorafenib and/or IFNα therapy. Results: IL-6 has no direct effect on cell proliferation and invasion but promotes cell apoptosis and up-regulate IL-33 and VEGF-A expression. IL-6 could attenuate the anti-proliferation effect by sorafenib and combination therapy but facilitate the pro-apoptosis of the combination therapy and augment the pro-invasive effect induced by single treatment. IL-6 could down-regulate p-STAT3, however up-regulate the p-MEK/p-ERK and NF-kB/iNOS expression, and it also facilitated the promotion on p-JAK2 and p-MEK/p-ERK by either sorafenib or IFN-α. in vivo study, IL-6 significantly promotes tumor growth. The combination treatment showed the highest inhibition on tumor growth which is derived from HCCLM3-IL6(-) cells. Conclusions: IL-6 has no direct effect on cell proliferation and invasion but promotes tumor cell apoptosis in vitro study. Sorafenib and combination therapies are suitable for HCC cells with low or no IL-6 expression confirmed in vivo study.

In wireless networks, the performance is degraded by the intensity of the interference received from concurrent transmissions. Considering a stochastic cache-enabled network where some users have caching ability to store the most popular packets, we propose a novel interference management scheme to eliminate the interference by exploiting the content diversity. First, cache-enabled users can exploit cached packets as side information to cancel the interference. Second, considering that different access points may transmit the same contents to different users simultaneously, they should be regarded as useful signals rather than interference. The performance improvement with these two content diversity schemes is theoretically analyzed in this paper. The probabilities for the interference cancellation case and the signal enhancement case are derived, respectively, followed by the investigation of the signal to interference plus noise ratio improvement with our proposed content diversity schemes. Based on this, the effective content capacity of the system is analyzed. In addition to the simulations to validate the accuracy of the theoretical analysis, the impacts of caching ability and the proposed interference management schemes on the effective content capacity are investigated.

To evaluate the role of circulating tumour cells (CTCs) in patients with endometrial cancer (EC).This study included 40 patients with a pre-operative diagnosis of high-risk EC between April 2015 and May 2016. Patients were further divided into high-risk (grade 3, non-endometrioid, myometrial invasion ≥1/2 and stage III-IV) and high-intermediate-risk (grade 2-3, endometrioid, myometrial invasion1/2 and stage I-II) groups according to postoperative pathological results. CTCs were detected using the CellSearch system, and CTC results were correlated with standard clinicopathological characteristics and serum tumour marker CA125/HE4 status using Chi-squared test, continuity correction or Fisher's exact test. The pharmacodynamic effect was detected after the first cycle of adjuvant therapy. Patients were followed up for 13 months to assess outcomes.Fifteen percent of patients had one or more CTCs. The presence of CTCs was found to be significantly associated with cervical involvement (83.33% vs 11.76%, p=0.00). No significant difference in CTC-positive rates was detected between the high-risk and high-intermediate-risk groups, and no significant correlation was found between CTCs and serum CA125/HE4, either by positive rates or exact serum levels of the conventional tumour markers. No more CTCs were detected after the first cycle of standard chemotherapy in this study, and no distant metastases or recurrence were found in the CTC-positive patients during the follow-up period.The presence of CTCs was correlated with cervical involvement. Early-stage EC patients with CTCs may benefit from additional adjuvant therapies. Assessment of CTCs may be useful in the management of high-risk EC patients.

The forkhead/winged helix transcription factor Foxa2 is a major upstream regulator of Pdx1, a transcription factor necessary for pancreatic development. In the present study, we conditionally knocked out Foxa2 in Pdx1-expressing domain and further analyzed the contribution of Foxa2 to α- and β-cell development and the effect of Foxa2 deletion on plasma insulin, glucagon, and glucose levels. Homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice were generated by homologous recombination using a Foxa2 gene-targeting vector. α- and β-cell mass was examined by immunofluorescence microscopy. Plasma glucose, insulin, and plasma were measured at postnatal day 10. For pdx1 lineage tracing studies, heterozygous pdx1 Foxa2 EYFP and homozygous pdx1 Foxa2 EYFP mice were used. Our immunofluorescence analysis revealed that in the pancreas sections of the homozygous mutant mice, Foxa2 was virtually absent from non-β cells and its expression almost exclusively coincided with remnant β cells. The density of both α and β cells apparently decreased in the pancreas of the heterozygous mutant mice and in the pancreas of the homozygous mutant mice, α cells lost its predominance and β cells increased proportionally. Direct Pdx1 cell lineage tracing revealed that, on embryonic day 18.5, in the homozygous mutant mice, Pdx1 expression coincided almost exclusively with that of insulin-secreting β cells. Chemiluminescence assays revealed that heterozygous pdx1 Foxa2 mice had significantly lower insulin levels than control mice (P0.01). However, no apparent difference was observed between homozygous pdx1 Foxa2 mice and control mice (P0.05). Chemiluminescence assays also showed that Foxa2 deletion significantly depressed plasma glucagon levels in both homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice (P0.01 vs. controls). Plasma glucose on postnatal day 10 was significantly lower in homozygous pdx1 Foxa2 mice compared with control mice (P0.01). Our study demonstrates that homozygous Foxa2 ablation leads to an imbalance in β/α ratio, profound hypoglucagonemia, inappropriate hyperinsulinemia, and hypoglycemia in mice. Our conditional tissue-specific Foxa2 ablation mouse model will be useful in elucidating regulation of normal and abnormal α- and β-cell differentiation and pinpointing novel targets for diabetes control.

Hypothyroidism is a common condition of hormone deficiency, and oral administration of thyroid hormones is currently the only available treatment option. However, there are some disadvantages with this treatment modality including compliance challenges to patients. Therefore, a physiologically based alternative therapy for hypothyroidism with little or no side-effects is needed. In this study, we have developed a method for microencapsulating porcine thyroid cells as a thyroid hormone replacement approach. The hybrid wall of the polymer microcapsules permits thyroid hormone release while preventing immunoglobulin antibodies from entry. This strategy could potentially enable implantation of the microcapsule organoids containing allogeneic or xenogeneic thyroid cells to secret hormones over time without the need for immunosuppression of recipients. Porcine thyroid cells were isolated and encapsulated in alginate-poly-L-ornithine-alginate microcapsules using a microfluidic device. The porcine thyroid cells formed three-dimensional follicular spheres in the microcapsules with decent cell viability and proliferation. Thyroxine release from the encapsulated cells was higher than from unencapsulated cells ( P 28 days). These results suggest that the microencapsulated thyroid cell organoids may have the potential to be used for therapy and/or drug screening.

In the original publication of this article [1], there are mistakes in Fig. 3A and Fig. 3D.

This paper presents a method to beautify Chinese characters and a way to evaluate the beautification result. In order to make handwritten Chinese characters more in line with the aesthetic standards of Chinese characters, 52 Chinese characters were selected as experimental data. These data covered 33 standard strokes and 19 typical structures of Chinese characters. The handwritten Chinese characters were beautified mainly from two aspects-the global adjustment and the elimination of jitter. Firstly, the two-dimensional (2D) data points set is extended into three-dimensional (3D) space. Then the Gaussian Mixture Model (GMM) is established for the data set, and the layout of handwritten Chinese characters is adjusted by point set registration algorithm. Secondly, according to the properties of the cubic Bezier curve function, detect the jitter of each strokes, and eliminate the jitter by interpolation algorithm. The evaluation of the results after beautification has always been limited to subjective evaluation. This paper attempts to combine the evaluation of beautification result with machine learning methods. Handwritten Chinese character recognition (HCCR) is used as the tool. Experiments show that the overall layout and jitter of handwritten Chinese characters have been adjusted and deleted, and the evaluation of handwritten Chinese characters beautification results has its research significance.

This paper presents an innovative method to align two handwritten Chinese characters modeled by three-dimensional point sets. A piecewise cubic Bezier curve is first defined for each character stroke, interpolating the 2D sample points. The density of sample points is then adjusted along the curve for even distribution. Later all 2D points are extended into 3D space to integrate additional geometry information. Registration is then performed between two 3D point sets using Gaussian Mixture Model (GMM). This paper establishes the registration by minimizing the Euclidean Distance(L2) between two GMMs and then apply transformation accordingly. The key idea of this process is to include extra geometric information of the calligraphy to facilitate the registration process, using simple algorithms. Through the alignment and transformation process, the global layout of character is adjusted, but with local features retained. This technique can be applied in the morphing and beautification of Chinese calligraphy.

Background: Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract, and chronic calculous cholecystitis (CCC) is associated with an increased risk of GBC mortality. Understanding the relationship between CCC and its carcinogenesis might enable us to prevent and cure GBC. In this study, we attempted to explore microbiome profile changes during the transition from chronic cholecystitis mucosae to malignant lesions. Methods: Seven paired human GBC and CCC samples were obtained from patients who underwent radical cholecystectomy or laparoscopic cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate the microbiota changes between the two groups. Findings: Seven paired human GBC and CCC samples were obtained from patients who underwent radical cholecystectomy or laparoscopic cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate the microbiota changes between the two groups. We found that GBC patients and CCC patients shared similar stable and permanent dominant species and apparent differences in their biliary microbial composition and gene function. Peptostreptococcus_stomatis and Enterococcus_faecium may have potentially role in GBC progression. In addition, metagenomic species profiles, co-abundance and co-exclusion correlations and CAZyme prevalence showed significant differences between the CCC and GBC groups. Interpretation: Our data suggest microbiota changes between CCC and GBC, which might help us deepen our understanding of the complex landscape of different microbiotas in the development of GBC. Funding Statement: This study was supported by the National Natural Science Foundation of China (31600075), Shanghai Key Laboratory of Biliary Tract Disease Research Foundation (17DZ2260200), the National Natural Science Foundation of China (No. 81572819, 81773043,91440203, 31601021), the Peak Plateau Discipline Construction Project of Shanghai Jiaotong University School of medicine (No. 20181808), the Program of Shanghai Academic Research Leader (No. 19XD1422700), the Shanghai Natural Science Foundation (No 17ZR1418500) and Shanghai Pujiang Program (No 17PJD025). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of Xinhua Hospital affiliated with the Shanghai Jiao Tong University School of Medicine (No. XHEC-D-2019-049). All experiments were carried out in accordance with the approved guidelines. Informed consent was obtained from the patients.

// Wei Lu 1, 2, * , Yunping Hu 2, * , Qiang Ma 2, * , Linzhu Zhou 3 , Lin Jiang 2 , Zhizhen Li 2 , Shuai Zhao 2 , Yuzhen Xu 4 , Weibin Shi 1 , Sheng Li 5 , Yingbin Liu 1, 2 1 Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China 2 Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China 3 Institute of Chemistry, Shanghai Jiao Tong University, Shanghai, China 4 Department of Gastrointestinal Surgery, Xu Zhou Center Hospital, Affiliated to Medical College of Southeast University, Jiangsu, China 5 Department of Biochemistry, Dalian Medical University, Liaoning, China * These authors contributed equally to this work Correspondence to: Sheng Li, email: lisheng@dmu.edu.cn Wei Lu, email: wellu@163.com , wellu@sjtu.edu.cn Yingbin Liu, email: liuybphd@126.com Keywords: miR-223, gallbladder cancer, malignancy, STMN1 Received: January 25, 2016 Accepted: August 23, 2016 Published: August 26, 2016 ABSTRACT Background: MicroRNAs (miRs) are involved in cancer carcinogenesis, and certain regulatory miRs could provide promising therapeutic methods for refractory malignancies, such as gallbladder cancer (GBC). miR-223 was found to play a pivotal role in enhancing chemotherapeutic effects, therefore evoking interest in the role of miR-223 in GBC. Results: miR-223 was decreased in GBC tissues and cell lines, and ectopic miR- 223 expression exhibited multiple anti-tumorigenic effects in GBC cells, including decreased proliferation, migration and invasion in vitro . However, treatment with a miR-223 inhibitor increased cell viability. We determined that STMN1 was negatively correlated with and regulated by miR-223 in GBC. miR-223 increased GBC sensitivity to docetaxel in vitro and in vivo , and the induced sensitivity to docetaxel was suppressed by the restoration of STMN1 expression. Methods: We examined miR-223 expression in GBC tissue and GBC cell lines using qRT-PCR. The effects of modulated miR-223 expression in GBC cells were assayed using Cell Counting Kit-8 (CCK8), flow cytometry, and wound-healing and invasion assays. Susceptibility to docetaxel was evaluated in miR-223/STMN1-modulated GBC cells and xenograft tumor models. The protein expression of relevant genes was examined by Western blotting. Conclusions: These findings indicated that miR-223 might serve as an onco-suppressor that enhances susceptibility to docetaxel by downregulating STMN1 in GBC, highlighting its promising therapeutic value.

// Xiangliang Yuan 1, * , Weiwei Wang 1, * , Junhua Li 1, * , Peiming Zheng 1 , Ping Dong 2 , Lei Chen 2 , Yunlan Zhou 1 , Guohua Xie 1 , Dakang Xu 3, 4 , Yingbin Liu 2 , Lisong Shen 1 1 Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China 2 Department of Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China 3 MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia 4 Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 311121, China * These authors have contributed equally to this work Correspondence to: Lisong Shen, email: lisongshen@hotmail.com Keywords: gelsolin, gastric cancer, metastasis, PKR, p38MAPK protein kinase Received: May 18, 2015 Accepted: July 05, 2016 Published: July 13, 2016 ABSTRACT The biological function of gelsolin in gastric cancer and its mechanism remained undefined. Here, we demonstrated that gelsolin was down-regulated in human gastric cancer tissues, and lower tumorous gelsolin significantly correlated with gastric cancer metastasis. Functionally, gelsolin suppressed the migration of gastric cancer cells in vitro and inhibited lung metastasis in vivo . In mechanism, gelsolin decreased epithelial–mesenchymal transition (EMT) inducing cytoskeleton remolding through inhibition of p38 signaling to suppress the migration of gastric cancer cell. Moreover, gelsolin bound to and decreased the phosphorylation of PKR, and then inhibited p38 signaling pathway. Finally, similar to the gastric cancer cell lines, PKR-p38 signaling pathway proteins tend to be activated and correlated with low expression of gelsolin in clinical gastric cancer tissues. Altogether, these results highlight the importance of gelsolin in suppression of gastric cancer metastasis through inhibition of PKR-p38 signaling pathway.

A series of close-in underwater blast tests were performed on sandwich panels consisting of two aluminum alloy face-sheets and a honeycomb core to investigate blast resistance of metallic sandwich panels. The blast resistance of sandwich panels was assessed in terms of structural deformation resistance represented by back face-sheet deflection and intensity of the secondary pressure wave, which is determined by the maximum velocity of the back face-sheet. It was found that the secondary pressure wave shows an inverse trend with face-sheet thickness while a positive relationship with core density, which is determined by foil thickness in this study. A failure mode map was adopted to indentify the effect of design parameters on the structural failure mechanism at this blast magnitude. Finally, a comparison of underwater blast resistance between sandwich panels and monolithic plates of equivalent mass was performed. The comparative study provided further experimental evidence for the benefit of sandwich construction in terms of deformation resistance and secondary pressure wave intensity even at high blast magnitude. It was also suggested that the benefit of deformation resistance was amplified with increase in equivalent thickness.

Gallbladder cancer (GBC), the most common malignancy of the bile duct, is highly aggressive and has an extremely poor prognosis, which is a result of early metastasis. As it is regulated being at multiple levels, the metastatic cascade in GBC is complex. Recent evidence suggests that microRNAs (miRNAs) are involved in cancer metastasis and are promising therapeutic targets. In this study, miR-101 was significantly downregulated in tumor tissues, particularly in metastatic tissues. In GBC patients, low miR-101 expression was correlated with tumor size, tumor invasion, lymph node metastasis, TNM stage, and poor survival. Moreover, miR-101 was an independent prognostic marker for GBC. Additionally, miR-101 inhibited GBC cell proliferation, migration, invasion, and TGF-β-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the gene encoding the zinc finger protein X-linked (ZFX) was identified as a direct target of miR-101. More importantly, miR-101 significantly reduced activation of the MAPK/Erk and Smad signaling pathways, resulting in inhibition of TGF-β-mediated induction of EMT. Altogether, our findings demonstrate a novel mechanism by which miR-101 attenuates the EMT and metastasis in GBC cells and suggest that miR-101 can serve as a potential biomarker and therapeutic target for GBC management.

Limited by current clinical diagnosis techniques, gallbladder cancer remains a highly lethal disease and is associated with an extremely poor prognosis and treatment outcome. In an effort to overcome these severe obstacles, targeted nanoscale contrast agents have been developed and used in the past to increase the sensitivity and specificity of cancer detection. The development of targeted nanoscale contrast agents would offer an even more promising approach for gallbladder cancer diagnosis and subsequent treatment. In this study, a targeted nanoscale contrast agent was developed by conjugation of a CLIC1 antibody to carboxylated multi-walled carbon nanotubes (MWCNTs). Using a gallbladder cancer tumor xenograft model, it could be shown that intravenous injection of this tumor-targeted contrast agent to tumor-bearing mice exhibited a rapid photoacoustic signal with high intensity, leading to contrast enhancement of the entire tumor region. Mice injected with an untargeted contrast agent did not exhibit obvious tumor enhancement. We were able to show that CLIC1 antibody conjugated to nanoscale contrast agents proves to be highly beneficial for this fast and sensitive imaging technique for gallbladder tumors. Taken in concert, the results obtained indicate that the development of targeted nanoscale imaging probes offers a promising approach for the early detection and subsequent treatment of gallbladder cancer.

Objective: To evaluate the feasibility and safety of total mesopancreas excision (TMpE) in the treatment of pancreatic head cancer. Methods: The clinical and pathological data of 120 patients with pancreatic head cancer who had undergone TMpE in our center from May 2010 to January 2014 were retrospectively analyzed. Results: The mean operative time was (275±50.2) min and the average intra-operative blood loss was (390±160.5) mL. Post-operative complications were reported in 45 patients, while no peri-operative death was noted. The specimen margins were measured in three dimensions, and 86 patients (71.6%) achieved R0 resection. Conclusions: TMpE is safe and feasible for pancreatic head cancer and is particularly helpful to increase the R0 resection rate.

In the original version of [this article][1] ([1][2]), there are errors in Figs. 1D and H and 5B. Specifically, in Fig. 1D, the same migration assay image was used in the second and seventh panels, and an overlapping image was used in the third and fourth panels. In addition, the same migration

The present issue of Annals of Pancreatic Cancer is a special one co-edited by Dr. Yingbin Liu, Chair of the Department of General Surgery and dedicated to the Eighth Xinhua International Surgical Forum.

Background As a multicentre, randomized, double-blind phase II trial, ALTER 1202 (NCT03059797) suggests that anlotinib is a promising treatment option for patients with relapsed SCLC who failed ≥ 2 lines of chemotherapy. The median progress-free survival (PFS) was significantly longer in the anlotinib group compared with the placebo group (4.1 months vs 0.7 months; HR 0.19, 95% CI 0.12 to 0.32], P Methods Eligible either limited- or extensive-stage SCLC patients with disease progression after ≥ 2 lines of chemotherapy were randomized 2:1 to anlotinib or placebo (12 mg PO QD from day 1 to 14, every 3 weeks). The primary endpoint was PFS. OS was a pre-specified secondary endpoint. Results Between March 2017 and May 2018, 120 patients from 11 centers were randomized to either anlotinib arm (n = 82) or placebo arm (n = 38). In the final analysis (04 APR 2019), median OS was significantly prolonged about 2.4 months in anlotinib arm (7.3 months vs 4.9 months). OS at this date showed 60 events in anlotinib arm and 33 events in placebo arm (HR 0.53, 95%CI 0.3-0.8; p = 0.0029). Six-month, 1-y survival rates were 63.9%, 30.6% in the anlotinib group and 32.7%, 13.1% in the placebo group. The hazard ratio for OS favored anlotinib in most subgroups, especially for patients with brain metastases (OS 6.3m vs 2.6m; HR 0.23, 95%CI 0.09-0.59; p = 0.0009) and patients that received study drug as third-line therapy (OS 7.3m vs 4.9m; HR 0.50, 95%CI 0.31-0.82; p = 0.0051). No newly adverse events were observed. Conclusions The updated results showed that anlotinib prolonged not only PFS but also OS significantly than placebo with favorable safety profile. These data suggested that anlotinib is a promising treatment option for patients with relapsed SCLC who have experienced treatment failure with two lines of chemotherapy. Clinical trial identification NCT03059797. Legal entity responsible for the study Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Funding Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Disclosure All authors have declared no conflicts of interest.

Background/Aims: The role of ZFX in tumourigenesis is unclear. We aimed to study ZFX expression, regulation, and function and the clinical implications of this protein in human pancreatic cancer (PCa). Methods: One hundred and twenty patients with histologically confirmed PCa who underwent surgery were recruited for this study. Tumour samples and PCa cell lines were used to examine ZFX. Various cell functions related to tumourigenesis were assessed. In vivo mouse tumour xenografts were used to confirm the in vitro results. Results: Patients with ZFX-positive tumours had worse overall survival than patients with ZFX-negative tumours. The depletion of ZFX using lentiviral shRNAs significantly inhibited cell proliferation by inducing cell cycle arrest in G0/G1 phase and resulted in increased cell apoptosis and invasive repression. In vivo studies confirmed that ZFX promoted tumour growth. Mechanistically, MAPK pathway activation was involved in the oncogenic functions of ZFX. Conclusions: ZFX acts as a putative oncogene in PCa and could be a novel therapeutic target for this disease.

There has been continuous effort to reduce the cost of III-nitride devices for market penetration of solid state lighting as well as the next generation of power device applications. Using high throughput MOCVD platform is one of the critical drivers to reduce the cost of ownership (CoO) of various light emitting diodes (LED) products. GaN based LEDs grown on 4” patterned sapphire substrates (PSSs) is the primary method for LED manufacturers to further lower CoO. Here we report LED growth on 4” PSSs with the highest throughput MOCVD platform, AMEC Prismo A7TM High quality GaN based single layer materials and LEDs have been grown on both normal 4” PSSs and PSSs with AlN buffer prepared by physical vapor deposition (PVD). Excellent thickness uniformity of less than 1.5% and wavelength uniformity of less than 1.5 nm (1σ with 2 mm edge exclusion) have been achieved for green and blue LEDs on 4” PSSs and PSSs with PVD AlN. In addition, initial results for LEDs growth on 6” PSSs are also reported in this paper.

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats.

Received October 31, 2014; Revised December 8, 2 December 8, 2014. From the Department of General Surgery, Xinhua Hos Jiao Tong University, School of Medicine, Shanghai (XLiu) and Department of General Surgery, Hangzhou Hospital, Hangzhou (X-A Wang, Cai, Jin, Shen, P Wang) Correspondence address: PingWang, MD, Hangzhou People’ No. 261 Huansha Rd, Hangzhou, China. email: 13906539 surgwxa@gmail.com

Hilar cholangiocarcinoma (HCC) remains one of the most difficult tumors to stage and treat. The aim of the study was to assess the diagnostic efficiency of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computer tomography (PET/CT) in evaluating the resectability of HCC. A systematic search was performed of the PubMed, EMBASE, and Cochrane databases. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for individual studies and pooled data as well as test for heterogeneity and public bias. Our data showed that CT had the highest pooled sensitivity at 95% (95% CI: 91–97), whereas PET/CT had the highest pooled specificity at 81% (95% CI: 69–90). The area under the curve (AUC) of CT, MRI, and PET/CT was 0.9269, 0.9194, and 0.9218, respectively. In conclusion, CT is the most frequently used imaging modality to assess HCC resectability with a good sensitivity and specificity. MRI was generally comparable with that of CT and can be used as an alternative imaging technique. PET/CT appears to be the best technique in detecting lymph node and distant metastasis in HCC but has no clear role in helping to evaluate issues of local resectability.

// Peng-Yuan Zhuang 1 , Jian-Dong Wang 1 , Zhao-Hui Tang 1 , Xue-Ping Zhou 1 , Yong Yang 1 , Zhi-Wei Quan 1 , Ying-Bin Liu 1 , Jun Shen 1 1 Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200082, China Correspondence to: Jun Shen, e-mail: junshen_xh@163.com Keywords: Neuropilin-1, vascular endothelial growth factor receptor-2, peritumoral tissue, overall survival, recurrence Received: August 04, 2014 Accepted: September 30, 2014 Published: October 11, 2014 ABSTRACT Purpose: To determined Neuropilin-1 (NRP-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression in the tumoral and peritumoral tissues of 214 treatment-naive HCC patients and its correlation with overall survival (OS) and time to recurrence (TTR). Experimental Design: NRP-1 and VEGFR-2 expression were examined by tissue microarray and peritumoral hypoxia by pimonidazole staining and angiogenesis by microvessel density (MVD). OS and TTR were evaluated by Kaplan-Meier analysis and log-rank test. Results: Peritumoral NRP-1 and VEGFR-2 expression were significantly higher than that of the tumoral tissue ( p 94.0 months) and TTR (>84.0 months). The multivariate Cox proportional hazards analysis revealed that patients with high peritumoral expression of both NRP-1 and VEGFR-2 were more than 4 times less likely to have recurrence ( p = 0.004) and more than 10 times likely to survive ( p < 0.001). Conclusions: Peritumoral NRP-1 and VEGFR-2 expression is associated with prolonged TTR and extended OS of HCC patients and both may be useful as predictors of surgical outcome of HCC patients and explored as potential therapeutic targets.

Background Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer. Methods Levels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins. Liver metastasis models and lung metastasis models were established to investigate the inhibitory effect of Dihydroartemisinin on gallbladder cancer metastasis. Results TCTP is aberrantly expressed in gallbladder cancer patients and associated with metastasis and a poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell division control protein 42 homolog (Cdc42) activation. In addition, in mice with xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder cancer cell metastases and improved survival. Conclusions These findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis.