Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China

Objective： To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs） in a Chinese population.Methods： We investigated 154 consecutive patients（88 males, 66 females; median age 56 years, age range 9-86 years） diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results： The pancreas was the most common site of involvement（63/154, 40.9%）. Tumor size varied from 0.3 to 16.0 cm（median, 1.2 cm）. The patients were followed up for a median period of 22 months（range, 1-157 months）. The estimated 3- and 5-year overall survival（OS） rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions： Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.

Clinical characteristics and prognostic analysis of gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN)

Objective： The aim of the study was to analyze the clinicopathologic characteristics of gastroenteropancreatic neuroendocrine neoplasm （GEP-NEN） and to explore the prognostic factors for patients and differences of immunohisto- chemical markers between neuroendocrine tumor （NET） and neuroendocrine carcinoma （NEC）. Methods： Retrospective reviews were conducted for the charts of 119 patients with GEP-NEN at the Affiliated Hospital of Qingdao University （China） from August 2003 to December 2013. Kaplan-Meier method was used to do the overall survivals analysis for the patients at different levels of predictive factors. Meanwhile, Cox proportional hazard model was used to select independent risk factors of surJival. Analysis of variance was used to compare the expression of immunohistochemical markers among different patho- logical grades. Results：Among 119 patients, pancreas （45/119, 37.82%） and rectum （33/119, 27.73%） were mostly involved. The onset age of GEP-NEN in female group was younger than that of the male group. There were 13 deaths （10.92%） during 18.9 （0.1-133.4） months follow-up period. Multivariate analysis indicated that neural invasion, gender and pathological grades of NET and NEC were independent risk factors. In neuroendocrine neoplasm （NEN）, Syn expression in G2 was higher than G1 and G3, while CgA showed no significant difference. All markers showed no significant differences between NET and NEC. Conclusion： GEP-NEN may occur at multiple sites of digestive system and lack specific clinical manifestations. Syn expression detected for the prognosis of G1, G2 and G3 tumors have clinical significance. Neural invasion, sex and patho- logical grades were independent prognostic factors for GEP-NEN patients. No significant difference was found in different pathological grades of NET and NEC.

Expressions and clinical significance of CD147 and CK19 in hepatocellular carcinoma

Objective: The aim of this study was to investigate the expressions of CD147 and CK19 in hepatocellular car- cinoma (HCC) and their clinical significance. Methods: The expressions of CD147 and CK19 were determined by tissue microarray and immunohistochemistry (IHC) in 272 cases of HCC and 81 cases of adjacent tumorous tissue. Results: The positive expression of CD147 in HCC and adjacent tumorous tissue was 73.53% (200/272) and 13.58% (11/81) with signifi- cant difference (P < 0.05). The positive expression of CK19 in HCC and adjacent tumorous tissue was 14.34% (39/272) and 0 (0/81) with significant difference (P < 0.05). The positive expression of CD147 were closely correlated to the histological grade, clinical stage, tumor-free survival, diameter of tumor and embolus of cancer in aqueduct or portal vein; but not to the patients' sex, age, liver cirrhosis, AFP level, infection of HBV, lymph node metastasis, number of tumor, invasion liver involucrum and the micro-satellites (P > 0.05). The expression of CK19 in HCC were closely correlate to the tumor-free survival, histological grade, diameter of tumor, liver cirrhosis, micro-satellites, lymph node metastasis and clinical stage; but not to patients' sex, age, number of tumor, invasion liver involucrum, AFP level, infection of HBV and embolus of cancer in aqueduct or portal vein (P > 0.05). Among the patients of positive expression of CD147, the median replacing time and overall survival were 13 and 24 months, lower than 48 and 60 months in the patients of negative expression (P < 0.05). Among the patients of positive expression of CK19, the median replacing time and overall survival were 7 and 13 months, lower than 31 and 42 months in the patients of negative expression (P < 0.05). The expression of CD147 had no correlation with the expression of CK19 (r = 0.061, P = 0.317). Conclusion: The positive of CD147 and CK19 closely correlate with the clinical prognosis of HCC, it may indicate poor prognosis of HCC.

Retinal damage after exposure to white light emitting diode lights at different intensities in Sprague-Dawley rats

Background:The usage of the light emitting diode(LED)has been increasingly applied in the illumination setting and electronic equipment.However,the effect of LED lights on the retina remains unclear.In this study,we observed and analyzed the impact of white LED lights at different intensities on the function and morphology of rat retinas.Methods:Thirty-six Sprague-Dawley rats weighing 150-180 g were randomly divided into six groups(n=6 in each group)including a normal control(NC)group,4 white LED groups at different light intensities(4,000,6,000,7,000,and 10,000 lux),and an ultraviolet B(UVB)lighting group(302 nm,1,000μw/cm2).After 24 hours of continuous illumination,full-field flash electroretinogram(FERG)and pathological examination were performed in each group.Results:As revealed by FERG,the impairment of retinal function gradually worsened with the increase of LED light intensity.In contrast,the UVB group had the most severe retinal function impairment.Particularly,the functional damage of rod cells and inner nuclear layer cells was the main FERG finding in each group.In the NC group,the retina had typical morphologies featured by well-defined structures,clearly visible border between the inner and outer segments,and neatly arranged inner and outer nuclear layer cells.After 24 hours of illumination,the inner and outer parts of the retina in the 4,000 lux group were still neatly arranged,along with a clear border;however,the inner and outer nuclear layers were randomly arranged,and some irregular nuclei and cells were lost.The damage of the internal and external retinal segments and the internal and external nuclear layers became more evident in the 6,000 lux group,7,000 lux group,and 10,000 lux group.The UVB group had a more obviously disordered arrangement of inner and outer nuclear layers and loss of cells.Conclusions:Continuous exposure to white LED light can cause structural and functional damage to rat retinas,and such damage is related to the intensity of illumination.Therefore,the risk of retinal damage should be considered during LED illumination,and proper LED illumination intensity may help to maintain eye health.

Sirolimus eye drops inhibit acute alkali-burn-induced corneal neovascularization by regulating VEGFR2 and caspase-3 expressions

Background:To investigate the effect of sirolimus(SRL)eye drops on acute alkali-burn-induced corneal neovascularization(CNV)and explore its possible mechanism.Methods:A total of 57 male Sprague-Dawley rats weighing 160-180 g were randomly divided into four groups including a normal control group(NC group,n=12),an untreated alkali-burned model control group(MC group,n=15),a blank eye drop treatment group(BT group,n=15),and an SRL eye drop treatment group(ST group,n=15).Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3,7,and 14 days after alkali exposure.Three rats were randomly sacrificed in each group before modeling and 3,7,14 days after modeling,and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.Results:Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC,BT,and ST groups 1 day after alkali exposure but were alleviated at day 3.The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7(F=9.77,P<0.05)and 14(F=5.81,P<0.05).At day 1,the corneal limbal vascular network was markedly filled.SNV was obvious at days 3,7,and 14.The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups,and the CNV scores showed significant differences among these groups(day 3:F=8.60,P<0.05;day 7:F=11.40,P<0.05;and day 14:F=41.59,P<0.01).Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups(F=0.52,P>0.05;F=0.98,P>0.05).The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3,7,and 14 days after alkali exposure,and there were significant differences in relative gray-scale values among these groups(day 3:F=32.16,P<0.01;day 7:F=85.96,P<0.01;day 14:F=57.68,P<0.01).The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3,7,and 14,and there were significant differences in relative gray-scale values among groups(day 3:F=32.16,P<0.01;day 7:F=53.02,P<0.01;day 14:F=38.67,P<0.01).Conclusions:SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models.It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue,which may contribute to the inhibition of alkali-burn-induced CNV.

A novel method to eliminate the bending-induced collapse of hexagonal honeycomb

A novel grooving method for eliminating the bending-induced collapse of hexagonal honeycombs has been proposed,which lies in determining the appropriate grooving parameters,including the grooving spacing,angle,and depth.To this end,a framework built upon the experiment-based,machine learning approach for grooving parameters prediction was presented.The continuously grooved honeycomb bending experiments with various radii,honeycomb types,and thicknesses were carried out,and then the deformation level of honeycombs at different grooving spacing was quantitatively evaluated.A criterion for determining the grooving spacing was proposed by setting an appropriate tolerance for the out-of-plane compression strength.It was found that as the curvature increases,the grooving spacing increases due to the deformation level of honeycombs being more severe at a smaller bending radius.Besides,the grooving spacing drops as the honeycomb thickness increases,and the cell size has a positive effect on the grooving spacing,while the relative density has a negative effect on the grooving spacing.Furthermore,the data-driven Gaussian Process(GP)was trained from the collected data to predict the grooving spacing efficiently.The grooving angle and depth were calculated using the geometrical relationship of honeycombs before and after bending.Finally,the grooving parameters design and verification of a honeycomb sandwich fairing part were conducted based on the proposed grooving method.

Spatial heterogeneity and compositional profiles of dissolved organic matter in farmland soils across China' Mainland

Dissolved organic matter(DOM) plays an essential role in many geochemical processes,however its complexity, chemical diversity, and molecular composition are poorly understood. Soil samples were collected from 500 vegetable fields in administrative regions of China' Mainland, of which 122 were selected for further investigation. DOM properties were characterized by three-dimensional excitation-emission matrix(3D-EEM) fuorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry(FTICRMS)(field intensity is 15 Tesla). Our results indicated that the main constituents were UVA humic-like substances, humic-like substances, fulvic acid-like substances, and tyrosine-like substances. A total of 10,989 molecular formulae with a mass range of 100.04 to 799.59 Da were detected, covering the mass spectrometric information of the soil samples from 27 different regions. CHO and CHON molecules were dominant in DOM, whereas lignin, tannins,and aromatic substances served as the main components. The results of cluster analysis revealed that the soil properties in Jiangxi Province were considerably different from those in other regions. The key backgrounds of the DOM molecular characteristics in the vegetablefield soil samples across China' Mainland were provided at the molecular level, with large abundance and great variability.

Confinement synthesis of bimetallic MOF-derived defect-rich nanofiber electrocatalysts for rechargeable Zn-air battery

Zn-air batteries with high energy density and safety have acquired enormous attention,while the practical application is hindered by the sluggish kinetics of the oxygen evolution reaction(OER)and the oxygen reduction reaction(ORR).In this work,a threedimensional(3D)defect-rich bifunctional electrocatalyst(CoFe/N CNFs)comprising irregular hollow CoFe nanospheres in Ndoped carbon nanofibers is presented,which is fabricated from CoFe ZIFs-derived(ZIF:zeolitic-imidazolate framework)polymer nanofibers precursor.The CoFe ZIFs with tunable particle size and composition are constructed using a confined synthesis strategy.Moreover,the Kirkendall diffusion process is available for forming the irregular hollow CoFe nanospheres,and the decomposition of polyvinylpyrrolidone(PVP)results in forming the defective carbon nanofibers,which provide more efficient active sites and enhance the electrocatalytic properties toward both OER and ORR.The optimized CoFe/N CNFs exhibit superior bifunctional activities,outperforming that of the benchmark Pt/C+RuO_(2) catalyst.As a result,the CoFe/N CNFs as an air-cathode endow the rechargeable Zn-air battery with an excellent power density of 149 mW·cm^(−2),energy density of 875 Wh·kg^(−1),and cycling stability.This work provides a new strategy to develop bifunctional electrocatalysts with desired nanostructure and regulated performance toward energy applications.

声带显微术后声休类型和持续时间的研究进展

声带显微手术是耳鼻咽喉科常见的手术之一,为提高声带显微手术患者术后的嗓音功能,通常建议患者术后声休,以促进声带黏膜的愈合。然而,声休的类型和持续时间仍没有一个标准方案,本文通过对国内外相关文献中的声休类型和持续时间进行探讨,期望为临床医生提供术后治疗思路,帮助患者更好地恢复嗓音功能。

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer(RATICAL):a nationwide multicenter retrospective study

Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene rearrangement.This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.Methods:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively analyzed.Interpretation training was conducted before the study was initiated.Quality controls were performed at participating centers using immunohistochemistry(IHC)-VENTANA-D5F3.The positive ALK gene rearrangement rate and consistency rate were calculated.The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.Results:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung adenocarcinoma.The quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma subgroup.For specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for RT-PCR.The overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients.These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

七次PH曲线G^2[C^1]Hermite插值方法

本文讨论七次PH (Pythagorean hodograph)曲线的G^2[C^1] Hermite插值问题. PH曲线是具有有理形式的等距线的一类多项式参数曲线,其弧长可精确计算,因此在CAD (computer aided design)中有着广泛的应用.本文采用平面参数曲线的复数表示形式,根据导矢曲线因式分解得到的多项式因子次数不同,将七次PH曲线分为3类.第1类七次PH曲线都是正则曲线,且其G^2[C^1]Hermite插值方法已经被研究.本文研究另外两类七次PH曲线的构造方法,并指出对于给定的初始条件,存在不超过6条的偶数条第2类七次PH曲线;而第3类七次PH曲线的存在性不仅对初始条件有约束,而且可以通过用户指定一个具有几何意义的实参进行交互构造.本文最后通过实例构造了这两类曲线对六分之一圆弧曲线的逼近.

五次间接PH曲线的几何特征

针对五次间接PH曲线的判别问题,本文结合高斯消元法与几何方法给出Bézier控制多边形满足的充分必要条件.间接PH曲线通过一个二次有理参数变换后,其等距线是有理形式的.间接PH曲线的代数充分必要条件本质是其一阶导数的因式分解满足特定条件,是一种积的形式.考虑到Bézier曲线的表示是Bernstein多项式形式,是一种和的形式.通过这两种形式的相容性引出待求解的非线性方程组并讨论求解问题,最后将所得结果应用在控制多边形上,得到五次间接PH曲线的几何特征.