CBLC promotes the development of colorectal cancer by promoting ABI1 degradation to activate the ERK signaling pathway.

CBLC (CBL proto-oncogene C) is an E3 ubiquitin protein ligase that plays a key role in cancers. However, the function and mechanism of CBLC in colorectal cancer (CRC) has not been fully elucidated. The aim of this study was to investigate the function of CBLC in CRC and its underlying molecular mechanism. High CBLC levels were certified in tumor tissues of CRC patients, and its expression was positively associated with TNM stage. Next, we explored the role of CBLC in CRC using gain or loss of function. For biological function analysis, CCK-8 cell proliferation, colony formation, flow cytometry, scratch, and transwell assays collectively suggested that CBLC overexpression promoted cell proliferation, cell cycle progression, migration and invasion. As observed, CBLC knockdown exhibited exactly opposite effects, resulting in impaired tumorigenicity in vitro. Xenograft studies displayed that CBLC overexpression accelerated tumor growth and promoted tumor metastasis to the lung, while the inhibitory effects of CBLC knockdown on tumorigenicity and metastasis ability of CRC cells was also confirmed. Furthermore, the molecular mechanism of CBLC in CRC was explored. CBLC induced the activation of ERK signaling pathway, further leading to its pro-tumor role. Notably, CBLC decreased ABI1 (Abelson interactor protein-1, a candidate tumor suppressor) protein levels through its ubiquitin ligase activity, while ABI1 upregulation abolished the effects of CBLC on the tumorigenesis of CRC. Taken together, these results demonstrate that CBLC acts as a tumor promoter in CRC through triggering the ubiquitination and degradation of ABI1 and activating the ERK signaling pathway. CBLC may be a potential novel target for CRC.

Formation mechanism of a novel core-shell with tetradecyl dimethyl benzyl ammonium-modified montmorillonite interlayer nanofibrous membrane and its antimicrobial properties.

A novel core-shell with a tetradecyl dimethyl benzyl ammonium chloride-modified montmorillonite (TDMBA/MMT) interlayer silk fibroin (SF)/poly(lactic acid) (PLLA) nanofibrous membrane was fabricated using a simple conventional electrospinning method. Scanning electron microscopy and pore size analyses revealed that this core-shell with TDMBA/MMT interlayer maintained its nanofibrous morphology and larger pore structure more successfully than SF/PLLA nanofibrous membranes after treatment with 75% ethanol vapor. Transmission electron microscopy and energy-dispersive X-ray spectroscopy analyses testified that the SF/PLLA-TDMBA/MMT nanofibers exhibited a core-shell with an interlayer structure, with SF/PLLA in the core-shell layer and TDMBA/MMT in the interlayer. The formation of a core-shell with interlayer nanofibers was primarily attributed to the uniform dispersion of TDMBA/MMT nanosheets in a solution owing to its exfoliation using hexafluoroisopropanol and then preparing a stable spinning solution similar to an emulsion. Compared to SF/PLLA nanofibrous membranes, the core-shell structure with TDMBA/MMT interlayers of SF/PLLA nanofibrous membranes exhibited enhanced hydrophilicity, thermal stability, mechanical properties as well as improved and long-lasting antimicrobial performance against Escherichia coli and Staphylococcus aureus without cytotoxicity.

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC-MS/MS methods for simultaneous determination of 19 main active components.

INTRODUCTION: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear. OBJECTIVES: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE. MATERIALS AND METHODS: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE. RESULTS: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE. CONCLUSION: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations.

Detection of fibrotic changes in the progression of liver diseases by label-free multiphoton imaging.

Collagen fibers play an important role in the progression of liver diseases. The formation and progression of liver fibrosis is a dynamic pathological process accompanied by morphological changes in collagen fibers. In this study, we used multiphoton microscopy for label-free imaging of liver tissues, allowing direct detection of various components including collagen fibers, tumors, blood vessels, and lymphocytes. Then, we developed a deep learning classification model to automatically identify tumor regions, and the accuracy reaches 0.998. We introduced an automated image processing method to extract eight collagen morphological features from various stages of liver diseases. Statistical analysis showed significant differences between them, indicating the potential use of these quantitative features for monitoring fibrotic changes during the progression of liver diseases. Therefore, multiphoton imaging combined with automatic image processing method would hold a promising future in rapid and label-free diagnosis of liver diseases.

Quantitative Assessment of Hepatic Steatosis Using Label-Free Multiphoton Imaging and Customized Image Processing Program.

Nonalcoholic fatty liver disease is rapidly becoming one of the most common causes of chronic liver disease worldwide and is the leading cause of liver-related morbidity and mortality. A quantitative assessment of the degree of steatosis would be more advantageous for diagnostic evaluation and exploring the patterns of disease progression. Here, multiphoton microscopy, based on the second harmonic generation and 2-photon excited fluorescence, was used to label-free image the samples of nonalcoholic fatty liver. Imaging results confirm that multiphoton microscopy is capable of directly visualizing important pathologic features such as normal hepatocytes, hepatic steatosis, Mallory bodies, necrosis, inflammation, collagen deposition, microvessel, and so on and is a reliable auxiliary tool for the diagnosis of nonalcoholic fatty liver disease. Furthermore, we developed an image segmentation algorithm to simultaneously assess hepatic steatosis and fibrotic changes, and quantitative results reveal that there is a correlation between the degree of steatosis and collagen content. We also developed a feature extraction program to precisely display the spatial distribution of hepatocyte steatosis in tissues. These studies may be beneficial for a better clinical understanding of the process of steatosis as well as for exploring possible therapeutic targets.

Use of 6-minute walk test for assessing severity of interstitial lung disease: an observational study.

BACKGROUND: The 6-minute walk test (6MWT) is a potential tool for assessing the severity of interstitial lung disease (ILD). OBJECTIVES: To explore the relationship between 6MWT results and traditional measures including pulmonary function and chest computed tomography(CT) and to determine factors that might influence the 6-minute walk distance (6MWD). METHODS: Seventy-three patients with ILD were enrolled at Peking University First Hospital. All patients underwent 6MWT, pulmonary CT, and pulmonary function tests and their correlations were analyzed. Multivariate regression analysis was used to identify factors that might impact 6MWD.  Results: Thirty (41.4%) of the patients were female and the mean age was 66.1 ± 9.6 years. 6MWD was correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO) and DLCO%pred. The decrease in oxygen saturation (SpO2) after the test was correlated with FEV1%pred, FVC%pred, TLC, TLC%pred, DLCO, DLCO%pred and the percentage of normal lung calculated by quantitative CT. The increase in Borg dyspnea scale was correlated with FEV1, DLCO and the percentage of normal lung. The backward multivariate model (F = 15.257, P < 0.001, adjusted R2 = 0.498) indicated that 6MWD was predicted by age, height, body weight, increase in heart rate, and DLCO. CONCLUSIONS: The 6MWT results were closely correlated with pulmonary function and quantitative CT in patients with ILD. However, in addition to disease severity, 6MWD was also influenced by individual characteristics and the degree of patient effort, which should thus be considered by clinicians when interpreting 6WMT results.

Zirconium Phosphate Assisted Phosphoric Acid Co-Catalyzed Hydrolysis of Lignocellulose for Enhanced Extraction of Nanocellulose.

The high mechanical strength, large specific surface area, favorable biocompatibility, and degradability of nanocellulose (CNC) enable it to be a potential alternative to petroleum-based materials. However, the traditional preparation of CNCs requires a large amount of strong acid, which poses a serious challenge to equipment maintenance, waste liquid recycling, and economics. In this study, a solid and easily recoverable zirconium phosphate (ZrP) was used to assist in the phosphoric acid co-catalyzed hydrolysis of lignocellulose for extracting CNCs. Due to the presence of acidic phosphate groups, ZrP has a strong active center with a high catalytic activity. With the assistance of ZrP, the amount of phosphoric acid used in the reaction is significantly reduced, improving the equipment's durability and economic efficiency. The effects of the process conditions investigated were the phosphate acid concentration, reaction temperature, and reaction time on the yield of CNCs. The Box-Behnken design (BBD) method from the response surface methodology (RSM) was applied to investigate and optimize the preparation conditions. The optimized pre-treatment conditions were 49.27% phosphoric acid concentration, 65.38 °C reaction temperature, and 5 h reaction time with a maximal cellulose yield (48.33%). The obtained CNCs show a granular shape with a length of 40~50 nm and a diameter of 20~30 nm, while its high zeta potential (-24.5 mV) make CNCs present a stable dispersion in aqueous media. Moreover, CNCs have a high crystallinity of 78.70% within the crystal type of cellulose Ⅰ. As such, this study may pioneer the horizon for developing a green method for the efficient preparation of CNC, and it is of great significance for CNCs practical production process.

Simultaneous superresolution reconstruction and distortion correction for single-shot EPI DWI using deep learning.

PURPOSE: Single-shot (SS) EPI is widely used for clinical DWI. This study aims to develop an end-to-end deep learning-based method with a novel loss function in an improved network structure to simultaneously increase the resolution and correct distortions for SS-EPI DWI. THEORY AND METHODS: Point-spread-function (PSF)-encoded EPI can provide high-resolution, distortion-free DWI images. A distorted image from SS-EPI can be described as the convolution between a PSF function with a distortion-free image. The deconvolution process to recover the distortion-free image can be achieved with a convolution neural network, which also learns the mapping function between low-resolution SS-EPI and high-resolution reference PSF-EPI to achieve superresolution. To suppress the oversmoothing effect, we proposed a modified generative adversarial network structure, in which a dense net with gradient map guidance and a multilevel fusion block was used as the generator. A fractional anisotropy loss was proposed to utilize the diffusion anisotropy information among diffusion directions. In vivo brain DWI data were used to test the proposed method. RESULTS: The results show that distortion-corrected high-resolution DWI images with restored structural details can be obtained from low-resolution SS-EPI images by taking advantage of the high-resolution anatomical images. Additionally, the proposed network can improve the quantitative accuracy of diffusion metrics compared with previously reported networks. CONCLUSION: Using high-resolution, distortion-free EPI-DWI images as references, a deep learning-based method to simultaneously increase the perceived resolution and correct distortions for low-resolution SS-EPI was proposed. The results show that DWI image quality and diffusion metrics can be improved.

Aberrant regulation of autophagy disturbs fibrotic liver regeneration after partial hepatectomy.

Reports indicate that autophagy is essential for maintaining hepatocyte proliferative capacity during liver regeneration. However, the role of autophagy in fibrotic liver regeneration is incompletely elucidated. We investigated the deregulation of autophagic activities in liver regeneration after partial hepatectomy using a CCl4-induced fibrosis mouse model. The baseline autophagic activity was significantly increased in the fibrotic liver. After 50% partial hepatectomy (PHx), liver regeneration was remarkably decreased, accompanied by increased hepatocyte size and binuclearity ratio. Moreover, the expression of autophagy-related proteins was functionally deregulated and resulted in a reduction in the number of autophagosome and autophagosome-lysosome fusions. We further showed upregulation of autophagy activities through verapamil administration, improved hepatocyte proliferation capacity, and restricted cellular hypertrophy and binuclearity ratio. In conclusion, we demonstrated that the impairment of liver regeneration is associated with aberrant autophagy in fibrotic liver and that enhancing autophagy with verapamil may partially restore the impaired liver regeneration following PHx.

Diagnosis of COVID-19 via acoustic analysis and artificial intelligence by monitoring breath sounds on smartphones.

Scientific evidence shows that acoustic analysis could be an indicator for diagnosing COVID-19. From analyzing recorded breath sounds on smartphones, it is discovered that patients with COVID-19 have different patterns in both the time domain and frequency domain. These patterns are used in this paper to diagnose the infection of COVID-19. Statistics of the sound signals, analysis in the frequency domain, and Mel-Frequency Cepstral Coefficients (MFCCs) are then calculated and applied in two classifiers, k-Nearest Neighbors (kNN) and Convolutional Neural Network (CNN), to diagnose whether a user is contracted with COVID-19 or not. Test results show that, amazingly, an accuracy of over 97% could be achieved with a CNN classifier and more than 85% on kNN with optimized features. Optimization methods for selecting the best features and using various metrics to evaluate the performance are also demonstrated in this paper. Owing to the high accuracy of the CNN model, the CNN model was implemented in an Android app to diagnose COVID-19 with a probability to indicate the confidence level. The initial medical test shows a similar test result between the method proposed in this paper and the lateral flow method, which indicates that the proposed method is feasible and effective. Because of the use of breath sound and tested on the smartphone, this method could be used by everybody regardless of the availability of other medical resources, which could be a powerful tool for society to diagnose COVID-19.

Verapamil induces autophagy to improve liver regeneration in non-alcoholic fatty liver mice.

Verapamil can restore intracellular calcium homeostasis, increase the fusion of autophagosomes and lysosomes, reduce lipid droplet accumulation and inhibit inflammation and insulin resistance in high-fat-fed mice. The present study aimed to investigate verapamil's effect and its underlying liver regeneration mechanism in mice with non-alcoholic fatty liver. After 50% hepatectomy was performed, the changes of autophagy and liver regeneration were evaluated by detecting cell proliferation and autophagy at each time point. Then, 25mg/kg verapamil was injected intraperitoneally for 10 d before an operation in the mild to moderate fatty liver and severe fatty liver groups. The control group and mild to moderate fatty liver group reached the peak of proliferation at 24-48h after operation, and the mice with severe fatty liver and steatohepatitis reached the peak at 48-72h. Autophagy in the normal group and mild to moderate fatty liver group reached the peak 48 hours after operation. Verapamil injection can enhance autophagy, reduce the weight of fatty liver mice, improve liver function and liver regeneration. Verapamil can induce autophagy, improve hepatocyte function and promote hepatocyte regeneration through the mTOR independent signaling pathway, thus improving the process of liver regeneration after partial hepatectomy.

A Prognostic Scoring System for Predicting Overall Survival of Patients with the TNM 8th Edition Stage I and II Hepatocellular Carcinoma After Surgery: A Population-Based Study.

PURPOSE: Postoperative prognosis prediction models for patients with stage Ⅰ and Ⅱ hepatocellular carcinoma (HCC) according to the 8th edition of the Tumor-Node-Metastasis staging system after surgery are rare. This study aimed to build a prognostic score to predict survival outcomes and stratify these patients into different prognostic strata. PATIENTS AND METHODS: We developed a web-based nomogram that incorporated four selected risk factors based on the multivariate Cox regression, using a training set (n=3567) from the Surveillance, Epidemiology, and End Results (SEER) database. It was validated with an independent internal set from the SEER database (n=1783) and an external validation set of 516 Chinese patients. The predictive performance and discrimination ability of our model were further evaluated and compared with those of the conventional HCC staging systems. RESULTS: Our nomogram consistently outperformed the conventional staging systems in the training, internal validation set, and external validation set. We quantified the nomogram model into a numerical SNIG (an abbreviation of the incorporated variables - size, number, MVI, and grade) score by summing the points assigned to each incorporated variable, leading to the optimal cut-off values of 6 and 10, which could stratify patients into 3 categories (SNIG score <6, 6-10, ≥10). This yielded significantly different median overall survivals (interquartile ranges) of 42.0 (20.0-72.0) and 37.0 (17.0-67.0); 28.0 (12.0-60.0) and 42.0 (21.75-82.0); 40.0 (18.0-70.0) and 29.0 (11.5-61.0) months for the 3 categories in the entire SEER and external validation sets, respectively. CONCLUSION: We developed a web-based SNIG model to graphically and numerically predict the overall survival of stage Ⅰ and Ⅱ HCC. This scoring system may shed light on risk stratification for these patients in clinical practice and clinical trials.

Geographic variations in the incidence of congenital hypothyroidism in China: a retrospective study based on 92 million newborns screened in 2013-2018 / 中华医学杂志(英文版)

BACKGROUND@#Although congenital hypothyroidism (CH) has been widely studied in Western countries, CH incidence at different administrative levels in China during the past decade remains unknown. This study aimed to update the incidence and revealed the spatial pattern of CH incidence in the mainland of China, which could be helpful in the planning and implementation of preventative measures.@*METHODS@#The data used in our study were derived from 245 newborns screening centers that cover 30 provinces of the Chinese Newborn Screening Information System. Spatial auto-correlation was analyzed by Global Moran I and Getis-Ord Gi statistics at the provincial level. Kriging interpolation methods were applied to estimate a further detailed spatial distribution of CH incidence at city level throughout the mainland of China, and Kulldorff space scanning statistical methods were used to identify the spatial clusters of CH cases at the city level.@*RESULTS@#A total of 91,921,334 neonates were screened from 2013 to 2018 and 42,861 cases of primary CH were identified, yielding an incidence of 4.66 per 10,000 newborns screened (95% confidence interval [CI]: 4.62-4.71). Neonates in central (risk ratio [RR] = 0.84, 95% CI: 0.82-0.85) and western districts (RR = 0.71, 95% CI: 0.69-0.73) had lower probability of CH cases compared with the eastern region. The CH incidence indicated a moderate positive global spatial autocorrelation (Global Moran I value = 0.394, P  < 0.05), and the CH cases were significantly clustered in spatial distribution. A most likely city-cluster (log-likelihood ratio [LLR] = 588.82, RR = 2.36, P  < 0.01) and 25 secondary city-clusters of high incidence were scanned. The incidence of each province and each city in the mainland of China was estimated by kriging interpolation, revealing the most affected province and city to be Zhejiang Province and Hangzhou city, respectively.@*CONCLUSION@#This study offers an insight into the space clustering of CH incidence at provincial and city scales. Future work on environmental factors need to focus on the effects of CH occurrence.

Graphene oxide coated shell-core structured chitosan/PLLA nanofibrous scaffolds for wound dressing.

Graphite oxide (GO) and chitosan (CS) nanofibers have aroused intense interest as wound dressing due to their physicochemical, antimicrobial properties and nanotopography. In this study, GO nanosheets were coated on shell (chitosan, CS)-core (L-polylactic acid, PLLA) structured nanofibrous scaffolds to create a synergistic microenvironment for wound healing. Through scanning electron microscopy (SEM) and atomic force microscopy (AFM) tests, results showed that the surface of GO-coated CS/PLLA nanofibers presented corrugated wrinkles and rougher than that of CS/PLLA nanofibers, and the GO nanosheets did not destroy the structure of nanofibers. X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA) demonstrated that GO nanosheets were successfully coated on CS/PLLA nanofibrous scaffolds. Furthermore, the coatings of GO nanosheets significantly improved the hydrophilicity of CS/PLLA nanofibrous scaffolds. GO-coated CS/PLLA nanofibrous scaffolds revealed more excellent antimicrobial activity to Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) than that of CS/PLLA nanofibrous scaffolds, meanwhile, they promoted the proliferation of pig iliac endothelial cells (PIECs). Rats wounds covered by GO-coated CS/PLLA nanofibrous scaffolds were healed better than other groups on pathological section. This type of nanofibrous scaffolds with GO nanosheets would possess an excellent potential in wound healing process.

Wedelolactone-Loaded Micelles Ameliorate Doxorubicin-Induced Oxidative Injury in Podocytes by Improving Permeability and Bioavailability.

Wedelolactone (WED) is commonly used for the treatment of doxorubicin (DOX)-induced kidney damage, but its efficacy is limited by its poor solubility and bioavailability. In this study, we developed a novel delivery system of WED-loaded micelles (WED-M) with Solutol® HS15 and lecithin at an optimized ratio of 7:3 to improve the poor permeability and bioavailability of WED and to enhance its efficacy. The spherically shaped WED-M (particle size: 160.5 ± 3.4 nm; zeta potential: -30.1 ± 0.9 mV; entrapment efficiency: 94.41 ± 1.64%; drug loading: 8.58 ± 0.25%; solubility: 1.89 ± 0.06 mg/ml) has continuous stability over 14 days and a sustained release profile. The permeability of WED-M in Caco-2 cells indicated a significant 1.61-fold higher Papp AP to BL ratio than WED alone. Additionally, pharmacokinetic evaluation of WED-M demonstrated that the bioavailability of WED was increased 2.78-fold. Both HE staining and transmission electron microscopy showed an obvious improvement of pathological damage in WED-M treatment. Moreover, WED-M significantly enhanced the ROS level in mice and MPC5 podocytes. We concluded that using this micelle delivery system for WED could improve its permeability and bioavailability to attenuate DOX-induced oxidative injury in podocytes. This study provided important information on the fact that the micelle delivery system, WED-M, showed a significant improvement of renal damage.

Pathological analysis of the superior mesenteric artery boundary in preoperative computed tomography of resectable pancreatic head adenocarcinoma.

The aim of the present study was to evaluate the biological and prognostic implications of the superior mesenteric artery (SMA) boundary on preoperative abdominal contrast-enhanced computed tomography (CE-CT) for resectable adenocarcinoma of the pancreatic head. A total of 121 patients treated over a 6-year period at Peking University Third Hospital (Beijing, China) were included in the present study. The pattern of the SMA boundary was investigated on preoperative CE-CT and detailed pathological analysis of the extrapancreatic plexus [the pancreatic head plexus II (PLX-II) located on the right edge of the SMA] was performed. The results revealed that the radiological SMA boundary was associated with the grade of parasympathetic neurogenesis (P=0.014) in PLX-II, and was predictive of postoperative disease-free survival (P=0.014) and liver metastasis (P=0.013). Therefore, it was proposed that extrapancreatic parasympathetic neurogenesis may account for the different patterns of the SMA boundary on preoperative abdominal CE-CT, and affect the prognosis, particularly for liver metastasis in resectable pancreatic head adenocarcinoma.

Wedelolactone alleviates doxorubicin-induced inflammation and oxidative stress damage of podocytes by IκK/IκB/NF-κB pathway.

The acute kidney injury(AKI) caused by nephrotoxic drugs contributes to inflammation and oxidative injury in podocytes. Wedelolactone (WED), a natural compound, is found with activities as anti-inflammation, anti-oxidative, anti-free radical,and etc. In this present study, MPC-5 cells were exposed to the nephrotoxic drugs doxorubicin (DOX). The results showed that WED significantly increased the SOD activity, CAT and GSH-Px levels, while significantly decreased the MDA content and ROS levels in DOX-induced MPC-5 cells. WED could also significantly decrease the levels of cytokines IL-6, MCP-1, TNF-α, and TGF-ß1. Additionally, the activation and phosphorylation of IκKα, IκBα and NF-κB p65 was inhibited by WED. The co-treatment of PDTC (NF-κB inhibitor) and WED significantly reduced NF-κB p65 phosphorylation. These findings suggested that WED alleviated inflammation and oxidative stress of doxorubicin-induced MPC-5 cells through IκK/IκB/NF-κB signaling pathway.

Clinicopathological features and prognosis factors for survival in elderly patients with pancreatic neuroendocrine tumor: A STROBE-compliant article.

To investigate the features and prognosis of the elderly patients with pancreatic neuroendocrine tumor (pNET).The patients diagnosed with pNETs between 2004 and 2014 were identified from the Surveillance Epidemiology and End Results database. The ethical approval was waived because the present study was analysis of the data from Surveillance Epidemiology and End Results database.A total of 4608 patients with "one primary only" histologically pNETs were confirmed and 653 were older than 75 years. Cancer-specific survival (CSS) and overall survival (OS) were examined. The elderly patients (≥75 years) have disadvantage in CSS and OS compared with younger cohort. Multivariate logistic regression revealed that the elderly patients have increased poorly differentiated composition, and decreased proportion of Black patients, receipt of surgery, married status, and number of removed lymph node. Multivariate Cox regression analysis demonstrated worse differentiation. Patients of T3-4 and M1 stage were associated with poor CSS, while patients of being female, tumor locating at pancreatic body/tail, receipt of surgery, and being married were associated with better CSS in the elderly patients. Meanwhile, patients with higher histological grade and M1 stage have poor OS, while patients with the characteristics of female, being married, tumor location at pancreatic body/tail and tumor surgery have better OS. Distant metastatic elderly patients underwent primary site surgery had better CSS and OS than the patients without surgery.The elderly patients have increased possibility of poorly differentiated tumor, and decreased proportion of Black patients, surgery of primary site, number of removed lymph node and married status. Worse differentiation and tumor metastasis were independent risk factors for both CSS and OS, while primary tumor located in body/tail of pancreas, female patients, surgery of tumor primary site, and being married were protective factors.

Extrapancreatic Neuropathy Correlates with Early Liver Metastasis in Pancreatic Head Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma has a devastatingly poor prognosis, and most prognostic factors reflected the tumor stage more than the tumors' biology. The peripheral nerve plexus is densely distributed in the tumor micro-environment, and there are interactions between tumor cells and these nerves. Perineural invasion is an important risk factor for tumor recurrence and metastasis in pancreatic head adenocarcinoma, but the concrete types of extrapancreatic neuropathy and its role in predicting prognosis are still not clear. OBJECTIVE: To clarify the role of extrapancreatic neuropathy in the early postoperative liver metastasis and tumor-related mortality in pancreatic head adenocarcinoma and to study the mechanism of tumor recurrence and liver metastasis in pancreatic head adenocarcinoma. METHODS: We reported a retrospective study of 60 patients with resectable pancreatic head adenocarcinoma, all of whom accepted radical pancreaticoduodenectomy. Plexus pancreaticus capitalis II (PLX-II) was the representation of extrapancreatic plexus in our study, and all of these plexus had immunohistochemical staining. We defined the postoperative tumor recurrence and tumor-related mortality within 6 months as the early prognostic indicators and analyzed the pathological alterations in PLX-II among different prognosis groups. RESULTS: There were 18 patients suffering early postoperative liver metastasis; these two groups differed significantly in the average number of nerve trunks (P<0.001), the proportion of neuritis (P=0.003), the content of sympathetic nerve fibers (P=0.004) and parasympathetic nerve fibers (P<0.001) per unit area of PLX-II. There were 15 patients suffering early postoperative mortality, and there were significant differences between these two groups in the average number of nerve trunks (P<0.001), the proportion of neuritis (P=0.009), the content of sympathetic nerve fibers (P=0.023) and parasympathetic nerve fibers (P<0.001) per unit area of PLX-II. CONCLUSION: The patterns of extrapancreatic neuropathy could reflect the biological behavior of resectable pancreatic head adenocarcinoma, and the pathological features of PLX-II were closely related to early liver metastasis and mortality.

Suppressing the Initial Growth of Sidewall GaN by Modifying Micron-Sized Patterned Sapphire Substrate with H3PO4-Based Etchant.

Micron-sized patterned sapphire substrates (PSS) are used to improve the performance of GaN-based light-emitting diodes (LEDs). However, the growth of GaN is initiated not only from the bottom c-plane but also from the sidewall of the micron-sized patterns. Therefore, the coalescence of these GaN crystals creates irregular voids. In this study, two kinds of nucleation layers (NL)-ex-situ AlN NL and in-situ GaN NL-were used, and the growth of sidewall GaN was successfully suppressed in both systems by modifying the micron-sized PSS surface.