Lymphatic microvessel density and vascular endothelial growth factor-C and -D as prognostic factors in breast cancer: a systematic review and meta-analysis of the literature

The use of lymphatic microvessel density (LVD) and pro-lymphangiogenic mediators as prognostic factors for survival in breast cancer remains controversial. We searched the electronic databases PubMed and EMBASE without language restrictions for relevant literature to aggregate the survival results. To be eligible, every study had to include the assessment of the LVD or the expression of vascular endothelial growth factor (VEGF)-C or -D in patients with breast cancer and provide a survival comparison, including disease-free survival (DFS) or overall survival (OS), according to the LVD, VEGF-C or VEGF-D status. Across all studies, 56.64?% of patients were considered to have a VEGF-C-positive tumor, and 65.54?% of patients had VEGF-D-positive tumors. High LVD had an unfavorable impact on DFS, with a pooled hazard ratio (HR) of 2.222 (95?% CI 1.579–3.126) and an OS with a HR of 2.493 (95?% CI 1.183–5.25). According to the different lymphatic makers, the subgroup HR in the D2-40 studies was 2.431 (95?%?CI 1.622–3.644) for DFS and 4.085 (95?% CI 1.896–8.799) for OS. VEGF-C overexpression, as assessed by immunochemistry, was a prognostic factor for decreased DFS (HR 2.164; 95?% CI 1.256–3.729) and for decreased OS (HR 2.613; 95?% CI 1.637–4.170). VEGF-D overexpression was a significant although weak prognostic factor for DFS only when assessed by immunochemistry, with a HR of 2.108 (95?% CI 1.014–4.384). Our meta-analysis demonstrated that LVD, VEGF-C and VEGF-D could predict poor prognosis in patients with breast cancer. However, standardization of the assessment of LVD and for the expression of lymphangiogenesis factors is needed.     

Blood vessel invasion as a strong independent prognostic indicator in non-small cell lung cancer: a systematic review and meta-analysis

Background and Objective

Blood vessel invasion plays a very important role in the progression and metastasis of cancer. However, blood vessel invasion as a prognostic factor for survival in non-small cell lung cancer (NSCLC) remains controversial. The aim of this study is to explore the relationship between blood vessel invasion and outcome in patients with NSCLC using meta-analysis.

Methods

A meta-analysis of published studies was conducted to investigate the effects of blood vessel invasion on both relapse-free survival (RFS) and overall survival (OS) for patients with NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the strength of this association.

Results

A total of 16,535 patients from 52 eligible studies were included in the systematic review and meta-analysis. In total, blood vessel invasion was detected in 29.8% (median; range from 6.2% to 77.0%) of patients with NSCLC. The univariate and multivariate estimates for RFS were 3.28 (95% CI: 2.14–5.05; P<0.0001) and 3.98 (95% CI: 2.24–7.06; P<0.0001), respectively. For the analyses of blood vessel invasion and OS, the pooled HR estimate was 2.22 (95% CI: 1.93–2.56; P<0.0001) by univariate analysis and 1.90 (95% CI: 1.65–2.19; P<0.0001) by multivariate analysis. Furthermore, in stage I NSCLC patients, the meta-risk for recurrence (HR = 6.93, 95% CI: 4.23–11.37, P<0.0001) and death (HR = 2.15, 95% CI: 1.68–2.75; P<0.0001) remained highly significant by multivariate analysis.

Conclusions

This study shows that blood vessel invasion appears to be an independent negative prognosticator in surgically managed NSCLC. However, adequately designed large prospective studies and investigations are warranted to confirm the present findings.     

灌溉、耕作和施氮对旱地农田土壤生态化学计量特征的影响

为了探讨灌溉、耕作和施氮对旱地农田土壤生态化学特征的影响,基于2019—2023年的3因素裂-裂区田间定位试验,设置主区为不灌溉（I0）和一次灌溉（I1）两个灌溉水平;裂区为翻耕（PT）、旋耕（RT）、深松（SS）三种耕作方式;裂-裂区为四种施氮模式,施氮时期因灌溉而异,I0下全部基施,I1下50%基施、50%灌溉前追施,但施氮量都分别为0（N0）、120（N120）、180（N180）和240（N240）kg/hm²,研究了2023年小麦成熟期0—100 cm整土及各土层土壤总碳（TC）、全氮（TN）、全磷（TP）含量及其生态化学计量比。结果表明：（1）对于0—100 cm土层整土,I1与I0相比,土壤TC、TN和TP含量分别降低35.1%、15.0%和2.4%,C∶N、C∶P和N∶P分别降低14.7%、24.6%和10.5%;除土壤TN含量和N∶P外,土壤其他养分含量及其生态化学计量比在耕作方式间存在显著差异;随施氮量的增加,土壤TN和N∶P呈现先增加后稳定的趋势,但土壤TC、TP、C∶N和C∶P无显著变化。（2）灌溉、耕作和施氮对土壤养分含量及其生态化学计量比的影响效应因土层而异。I1显著降低0—20 cm、20—40 cm、40—60 cm、60—80 cm和80—100 cm土层土壤TC和TN含量,但土壤TP含量仅在60 cm以下土层显著降低。其中,与I0相比,I1下土壤TC含量在各土层的降低幅度均随土层深度的增加而增大;土壤TN的降低幅度则随土层深度先降低后增加。SS较RT和PT能够提升各土层TC和TP含量,且提升幅度随土壤深度增加而减小。灌溉和耕作影响各土层的C∶N和C∶P,但灌溉仅对40 cm以下土壤N∶P有显著影响。施氮对土壤TN含量的影响随土层加深而减小,且不影响除土壤TN含量和表层土壤C∶N外的土壤养分含量及其生态化学计量比。（3）耕作和灌溉是影响旱地农田土壤养分和其生态化学计量比的主要因素,其贡献率分别为59%和19%,且灌溉可使耕作间的差异减小。总之,一次灌溉虽降低土壤TC、TN和TP含量及其比值,不利于土壤养分的维持,但其配合深松和施氮量180 kg/hm²可保障土壤肥力,实现旱地农田可持续发展。     

The Role of Teachers' Stories in the Staffroom of a Religious School

Women teachers in the staffroom of a religious high school in a small Israeli town are caught in a conflict between a modern consumer society that requires them to be educated career women, and the religious community of the town that requires them to be mothers and housewives. They solve the dilemma by turning the staffroom into an extension of their homes, by means of stories. The stories not only present the conflict to the teachers in the staffroom, but present the solution to the conflict.     

微针技术用于非经皮途径的药物递送研究进展

近年来,微针作为一种新兴的经皮给药技术,具有微创、无痛、使用方便和高效的特点,逐渐成为一种极具研究价值和应用潜力的给药策略。微针技术在过去20年中得到迅速发展并呈现出多样化的趋势,已可根据不同需求来定制微针的形状、组成、机械性能和其他特殊功能等。由于微针能以微创方式穿越各种生物屏障,因此许多研究人员探索了微针在除皮肤外各类组织和器官中的药物递送应用。本文综述了微针技术及其近年来在眼睛、血管、心脏等组织和器官的药物递送中的应用研究,以期推动微针技术的应用发展。     

基于比较代谢组学解析藤仓赤霉菌CGMCC 17793高产GA4机制

新型赤霉素(gibberellin) GA4因其独特的优势而具有广阔的应用前景。为探究GA₄生物合成调控机制,本研究以藤仓赤霉菌(Gibberella fujikuroi) GA₄生产菌株S (CGMCC 17793)和野生菌株Y (GenBank登录号：NRRL 13620)为研究对象,利用液相色谱-质谱联用(liquid chromatograph-mass spectrometer,LC-MS)代谢组学技术,结合主成分分析(principal component analysis,PCA)与偏最小二乘-显著性分析联合法(partial least squares-discrimination analysis,PLS-DA)等对两种菌株在同一发酵时间以及菌株S在不同发酵时间的差异代谢物进行筛选与鉴定,并利用KEGG数据库和MBROLE 2.0分析相关代谢通路。结果表明,与菌株Y相比,菌株S在发酵3、6、9 d时,显著上调和下调的代谢物分别为107种和66种、136种和47种、94种和65种。与生产菌株S发酵3 d时相比,6、9 d时显著上调和下调的代谢物分别为29种和40种、52种和67种。菌株S与菌株Y同一发酵时间的差异代谢物主要富集在氨基酸代谢、三羧酸循环(tricarboxylic acid cycle,TCA cycle)和萜类生物合成等通路。菌株S不同发酵时间的差异代谢物主要富集在氨基酸代谢与糖代谢等合成途径。通路注释与分析结果说明,菌株S通过促进氨基酸与糖代谢、TCA循环产生更多乙酰CoA,增强了甲羟戊酸途径,从而使萜类化合物合成的前体物质异戊烯焦磷酸(isopentenyl pyrophosphate,IPP)含量增加,最终提高了GA₄产量。本研究探究了藤仓赤霉菌GA₄代谢规律,为调控藤仓赤霉菌提高GA₄产量提供了理论基础。