Identification and validation of an autophagy-related long non-coding RNA signature as a prognostic biomarker for patients with lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is the most predominant pathological subtype of lung cancer, accounting for 40–70% of all lung cancer cases. Although significant improvements have been made in the screening, diagnosis, and precise management in recent years, the prognosis of LUAD remains bleak. This study aimed to investigate the prognostic significance of autophagy-related long non-coding RNAs (lncRNAs) and construct an autophagy-related lncRNA prognostic model in LUAD.MethodsThe gene expression data of LUAD patients were obtained from The Cancer Genome Atlas (TCGA) database. All autophagy-related genes were downloaded from the Human Autophagy Database (HADb). Spearman’s correlation test was exploited to identify potential autophagy-related lncRNAs. The multivariate Cox regression analysis was used to construct the prognostic signature, which divided LUAD patients into high-risk and low-risk groups. Subsequently, the receiver operating characteristic (ROC) curves were generated to assess the predictive ability of this prognostic model for overall survival (OS) in these individuals. Then, the Gene set enrichment analysis (GSEA) was conducted to execute pathway enrichment analysis. Finally, a multidimensional validation was exploited to verify our findings.ResultsA total of 1,144 autophagy-related lncRNAs were identified to construct the co-expression network via Spearman’s correlation test (|R²| >0.4 and P≤0.001). Ultimately, a 16 autophagy-related lncRNAs prognostic model was constructed, and the area under the ROC curve (AUC) was 0.775. The results of GSEA enrichment analysis showed that the genes in the high-risk group were mainly enriched in cell cycle and p53 signaling pathways. The results of the multidimensional database validation indicated that the expression level of BIRC5 was significantly correlated with the expression level of TMPO-AS1. Furthermore, both TMPO-AS1 and BIRC5 had a higher expression level in LUAD samples. LUAD patients with high expression levels of TMPO-AS1 and BIRC5 were correlated with advanced disease stage and poor OS.ConclusionsIn summary, our results suggested that the prognostic signature of the 16 autophagy-related lncRNAs has significant prognostic value for LUAD patients. Furthermore, TMPO-AS1 and BIRC5 are potential predictors and therapeutic targets in these individuals.     

Synthesis of well-defined star,star-block,and miktoarm star biodegradable polymers based on PLLA and PCL by one-pot azide–alkyne click reaction

Based on the “arm-first” strategy, ring-opening polymerization (ROP) and one-pot azide–alkyne click reaction, well-defined star-shaped polymers with different architectures have been successfully synthesized, including the star homopolymers four-arm star-shaped polycaprolactone (4sPCL) and four-arm star-shaped poly(l-lactic acid) (4sPLLA), star-block copolymer 4sPCL-b-PLLA and miktoarm star-shaped copolymer PCL₂PLLA₂. The star homopolymers 4sPCL and 4sPLLA were synthesized by a click reaction of an azide small molecule initiator and HC C-PCL or HC C-PLLA. The star-block copolymer 4sPCL-b-PLLA was synthesized by a click reaction of an azide small molecule initiator and the block copolymer HC C-PCL-b-PLLA. The miktoarm star polymer PCL₂PLLA₂ was synthesized by a one-pot azide–alkyne click reaction of simultaneous addition of equal proportions of HC C-PCL and HC C-PLLA. The structures of these star-shaped polymers have been confirmed by NMR, FT-IR and GPC. Furthermore, the melting and crystallization behaviors investigated using DSC and WXRD also confirm the formation of star-shaped polymers with different architectures.

Star, star-block, and miktoarm star biodegradable polymers were synthesized by an “arm-first” strategy, ring-opening polymerization and one-pot azide-alkyne click reaction.     

Efficient production of high-molecular-weight hyaluronic acid with a two-stage fermentation

In this paper, the production pattern of hyaluronic acid (HA) was revealed: the chain growth of HA mainly occurred in the first half of fermentation while the product accumulated throughout the fermentation period. Attempts were made to develop a two-stage fermentation process which provided high-level synthesis in both product titer and molecular weight. The pH was kept at 8.0 with a temperature of 31 °C in the first fermentation stage (0–10 h) to promote the growth of weight-average molecular weight (M_w), and the pH and temperature were maintained at 7.0 and 37 °C, respectively, in the following fermentation stage to facilitate HA accumulation. In addition, constant rates of aeration (1 vvm) and agitation (600 rpm) were adopted. The two-stage fermentation provided a balanced result in which a product titer of 4.75 g L⁻¹ and a M_w of 2.36 × 10⁶ Da were achieved under optimized conditions. The process introduces an effective way to produce HA considering the effect of segmented control strategy.

A two-stage fermentation process with a segmented control strategy provides high-level synthesis in both HA titer and molecular weight.     

Parenchyma-sparing hepatectomy improves salvageability and survival for solitary small intrahepatic cholangiocarcinoma

BackgroundThis study aimed to investigate the prognostic impact of parenchyma-sparing hepatectomy (PSH) on solitary small intrahepatic cholangiocarcinoma (ICC).MethodsA total of 184 patients with solitary small ICC (≤ 5 cm) from 2009 to 2017 were included. Short- and long-term outcomes were compared between PSH and Non-PSH approach.Results95 (51.6%) patients underwent PSH and 89 (48.4%) patients underwent Non-PSH for solitary small ICC. PSH was associated with less intraoperative blood loss (212.9 mL versus 363.5 mL, P=0.038), lower transfusion rate (7.4% versus 16.9%, P=0.048), without increasing the frequency of tumor recurrence (60.0% versus 58.4%). No significant differences were observed in overall survival (OS), recurrence-free survival (RFS) and liver RFS (P = 0.627, 0.769 and 0.538, respectively). 109 (59.2%) patients experienced recurrence, of these, 67 (36.4%) were intrahepatic recurrence. Subgroup analysis of patients with liver-only recurrence demonstrated an increased likelihood of repeat hepatectomy for PSH compared to Non-PSH (21.2% versus 2.9%, P = 0.031), thus resulting in improved liver OS (P = 0.016).ConclusionPSH was associated with improved perioperative outcomes but it did not increase liver recurrence rates. PSH offered an increased rate of salvage hepatectomy for recurrent tumor, thus improving long-term survival in cases in which liver recurrence occurred.     

机器人与开腹手术治疗肝内胆管细胞癌患者近期疗效研究*

目的 比较机器人与传统开腹手术行肝叶切除术治疗肝内胆管细胞癌(ICC)患者的安全性和短期疗效。方法 2019年1月～2020年12月我院诊治的ICC患者27例,其中9例接受机器人手术,18例接受传统开腹肿瘤根治术,比较两组手术情况。结果 两组均完成肿瘤根治术;机器人组和开腹组患者手术时间【(198±32)分对(215±74)分】、术中出血量【200(100,250) ml对(275(200,300)ml】和术中输血次数(0次对2次)均无统计学差异(P>0.05);机器人组和开腹组患者肿瘤直径【4.0(2.5,5.5) cm 对6.3(3.9,6.5) cm】、R0切除率(100.0%对88.0%)和淋巴结转移率(44.4%对38.9%)比较,差异无统计学意义(P>0.05);机器人组术后卧床时间和住院日分别为2(1,2.5)d和7(4,8)d,显著短于开腹组【分别为3(1.8,3.5)d和11(8,12)d,P<0.05】,机器人组住院费用为11.3(9.1,13.5)万,与开腹组的10.1(8.8,11.5)万比,无统计学差异(P>0.05);两组术后并发症发生率为11.1%和27.8%,无统计学差异(P>0.05)。结论 开展机器人肿瘤根治术治疗ICC患者安全,术后恢复快。     

NLR在COPD合并CAP与AECOPD患者中诊断与预后的意义

目的对比分析中性粒细胞与淋巴细胞比值(NLR)在慢性阻塞性肺疾病(COPD)合并社区获得性肺炎(CAP)和COPD急性加重期(AECOPD)患者中的鉴别诊断价值及评估预后的潜力。 方法选择2017年1月至2019年12月在哈尔滨医科大学附属第一医院呼吸内科及重症监护病房(ICU病房)符合条件的1 215例COPD患者为对象,依据诊断标准分为COPD合并CAP组783例和AECOPD组432例。使用Spearman相关分析,分析NLR与其他炎性指标(WBC、PCT、CRP、FIB)的相关性;绘制受试者工作特征(ROC)曲线,分析NLR对于COPD合并CAP与AECOPD的诊断价值及评估预后的潜力。 结果Spearman相关分析显示：两组的NLR与其他炎性指标均有明显相关性(P<0.001);ROC曲线分析显示对于3.987的NLR的截断值,鉴别两组的灵敏度为56%,特异性66%,AUC为0.627;NLR在预测ICU入住率、住院期间病死率、有创及无创机械通气使用率方面,COPD合并CAP组AUC分别为：0.79、0.773、0.791、0.726;AECOPD组AUC分别为：0.874、0.915、0.862、0.74。 结论NLR水平在一定程度上可以鉴别COPD合并CAP与AECOPD,但准确性不高;NLR较其他炎性指标在预测ICU入住率、住院期间病死率、机械通气使用率方面表现出显著优势。     

Discovery of Biaryl Amides as Potent,Orally Bioavailable, and CNS Penetrant RORγt Inhibitors

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Scorpion Toxin,BmP01, Induces Pain by Targeting TRPV1 Channel

The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.