Acute lung injury (ALI) resulting from bacterial infection poses a significant risk, and its etiology involves the complex interplay of harmful immune responses and blood coagulation. Despite this understanding, the roles and mechanisms of tissue factor pathway inhibitor (TFPI) in LPS-induced ALI remain insufficiently elucidated. In this study, we aimed to explore the effects of TFPI in LPS-induced ALI. Our investigations revealed that TFPI exerts multiple beneficial effects in LPS-induced ALI. Specifically, TFPI reduces microvascular permeability, Myeloperoxidase (MPO) activity, and cytokine production while inhibiting blood coagulation.Moreover, TFPI demonstrates the capacity to promote proliferation and suppress apoptosis in Human microvascular endothelial cells (HMEC-1) and Human umbilical vein endothelial cells (HUVEC) through the inhibition of the caspase pathway and mitochondrial apoptosis pathway.Furthermore, our findings indicate a correlation between tissue factor (TF) and TFPI expression, with TFPI regulation observed in HMEC-1 cells following LPS treatment. This novel insight suggests that TFPI plays a regulatory role in TF expression. Overall, the protective effect of TFPI on LPS-induced ALI is unveiled by its ability to enhance endothelial cell proliferation and inhibit apoptosis through the modulation of caspase and Bcl-2/Bax pathways. These results underscore the potential of TFPI as a promising therapeutic target for ALI treatment.

Immunotherapy based on programmed cell death protein receptor 1 and its ligand (PD-1/PD-L1) has become an important method for treating non-small cell lung cancer (NSCLC). Peptide-based and nanobody-based PET tracers offer potential advantages in PD-L1 detection, yet their comparative tumor uptake and biodistribution remain unclear. This study aimed to evaluate and compare [68Ga]Ga-DOTA-WL12 (a peptide-based tracer) and [68Ga]Ga-NOTA-RW102 (a nanobody-based tracer) in assessing PD-L1 expression in primary and metastatic NSCLC, providing insights for future radiotracer design and theranostic applications. Ten patients diagnosed with NSCLC underwent [68Ga]Ga-DOTA-WL12 and [68Ga]Ga-NOTA-RW102 PET/CT scans, with four of these patients also receiving [18F]FDG PET/CT scans. The tracer uptakes, quantified by maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and target-to-background ratio (TBR), were compared between [68Ga]Ga-DOTA-WL12 and [68Ga]Ga-NOTA-RW102 PET/CT. DOTA-WL12 and NOTA-RW102 exhibited favorable binding affinities with PD-L1, with equilibrium dissociation constant (KD) values of 0.2 nM and 0.0047 nM, respectively. Subsequent human studies revealed significant variations (P < 0.05) in the uptake of [68Ga]Ga-DOTA-WL12 and [68Ga]Ga-NOTA-RW102 across the liver (SUVmean: 20.43 ± 4.26 vs. 6.12 ± 1.36, p = 0.015), kidney (SUVmean: 2.40 ± 0.34 vs. 22.37 ± 2.88, P = 0.015), spleen (SUVmean: 2.44 ± 0.67 vs. 18.49 ± 3.90, P = 0.015), and lung background (SUVmean: 0.18 ± 0.12 vs. 1.09 ± 0.29, P = 0.015). Meanwhile, we found that the correlation between SUVmax and PD-L1 TPS was significantly stronger with [68Ga]Ga-DOTA-WL12 compared to [68Ga]Ga-NOTA-RW102 (P < 0.0001, r = 0.9471 vs. P = 0.0241, r = 0.5235). The uptake of peptide-based [68Ga]Ga-DOTA-WL12 was more strongly correlated with PD-L1 TPS in primary and metastatic tumor lesions compared to [68Ga]Ga-NOTA-RW102. They also displayed different distribution, suggesting that peptide-based and nanobody-based radiotracers may have different clinical implications, particularly in radiotherapy.

Assessing programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer (NSCLC), particularly in metastatic cases, remains challenging. In this study, surface plasmon resonance (SPR) analysis and [Ga-68]Ga-DOTA-WL12 micro-PET/CT imaging are performed. [Ga-68]Ga-DOTA-WL12 PET/CT and [F-18]FDG PET/CT are performed on a cohort of 20 patients with NSCLC. Semi-quantitative assessments include SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and target-to-background ratio (TBR). DOTA-WL12 exhibits robust PD-L1 binding with a KD value of 0.2 nM. Subsequent human studies reveal significant correlations between PD-L1 expression and the [Ga-68]Ga-DOTA-WL12 SUVmax in primary and metastatic lesions, surpassing the [F-18]FDG results (r = 0.8889, p <0.0001 vs r = 0.0469, p = 0.8127). Notably, [Ga-68]Ga-DOTA-WL12 imaging discerned SUVmax and TBR differences between PD-L1 TPS <= 1% and PD-L1 TPS > 1% groups (p all <0.001). In an NSCLC patient with brain metastases, [Ga-68]Ga-DOTA-WL12 shows a SUVmean of 0.04 in the brain background, with TBR values of 17 and 23, underscoring its potential for detecting brain metastases. The study provides initial evidence for the clinical utility of [Ga-68]Ga-DOTA-WL12 PET/CT for lesion detection, immunotherapy selection, and therapeutic efficacy evaluation in PD-L1-expressing NSCLC, demonstrating its potential as a valuable tool in NSCLC research and management.

Background: The accurate preoperative localization of pulmonary nodules is essential for a successful video-assisted thoracic surgery (VATS). The aim of this research was to clarify the efficacy and safety of CT-guided localization of pulmonary nodules by mixture of methylene blue and medical adhesive. Methods: Between January 2020 and January 2021, 103 subjects who have received the CTguidance pulmonary nodules localization operation were included and retrospectively analyzed. The data on efficiency and complications of preoperative localization using medical adhesives mixed with methylene blue mixture were collected and analyzed. Results: 103 patients with 111 localized pulmonary nodules were included, 95 of whom had one nodule and 8 of whom had two nodules. The nodule localization success rate reaches as high as 100 %. The mean diameter of pulmonary nodules was 9.50 +/- 3.67 mm. The mean distance of pulmonary nodule and pleural surface was 19.95 +/- 14.92 mm. The mean depth of localized adhesive in the lung parenchyma was 18.99 +/- 11.62 mm, and the mean time required for localization was 16.98 +/- 5.72 min. The average time from the nodule localization to VATS surgery was 16.97 +/- 7.34 h. The common complications of localization were minor pulmonary hemorrhage (9.74 %) and mild pneumothorax (15.53 %). Besides, pulmonary hemorrhage was related with depths of medical adhesives and nodules in lung parenchyma ( p = 0.018 and 0.002, respectively). Conclusion: Medical adhesive mixed with methylene blue is safe and effective in pulmonary nodules localization for VATS, and surgeons have flexibility in scheduling the procedure.

Supplementary Table 3 from TGFBR1 Haplotypes and Risk of Non–Small-Cell Lung Cancer

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-022-02409-y.

Objective:To compare the effects of thoracoscopic anatomical segmentectomy and thoracoscopic lobectomy on patients' respiratory function.Methods:Retrospective analysis of 326 patients who underwent thoracoscopic surgery from July 2016 to July 2019(209 patients underwent anatomical segmentectomy, 117 patients underwent lobectomy). According to variables including gender, age, tumor location, smoking history and BMI, two propensity score-matched cohorts including 89 patients respectively were constructed. The patients’ baseline data and respiratory function date of the patients pre-operation and post-operation were analyzed. The measurement data that obey the normal distribution were described by mean±standard deviation, and the t-test was used for comparison between groups; the measurement data of non-normal distribution was described by the median value( P25, P75), and the Wilcoxon rank sum test was used for the comparison between groups; The data was described by frequency, and the chi-square test or Fisher's exact probability method was used for comparison between groups. Results:At the first-month follow-up after surgery, there was no significant difference in the variation of FVC[(0.48±0.40)L vs.(0.34±0.37)L, P=0.215)and FEV1[(0.52±0.46)L vs.(0.43±0.77)L, P=0.364), and in the change rate of FVC(%)[15.23(8.74, 21.25) vs. 14.58(7.75, 19.40), P=0.122], FEV1(%)[17.25(9.56, 22.78) vs. 16.42(9.15, 20.28), P=0.154]and DLCO(%)[18.54(10.88, 25.68)vs. 17.45(9.58, 23.75) P=0.245]. Between the segmentectomy group and lobectomy group, there was a significant difference in the alteration of FVC[(0.50±0.47)L vs. (0.29±0.31)L, P=0.031] and FEV1[(0.44±0.34)L vs.(0.24±0.23)L, P<0.001], the change rate of FVC(%)[14.27(7.87, 22.32) vs. 9.95(5.56, 17.24), P=0.008]、FEV1(%)[15.23(8.36, 22.17)vs. 10.05(5.15, 18.54), P<0.001]and DLCO(%)[13.74(6.24, 19.78) vs. 4.45(-2.32, 13.75), P=0.023]in the 6th month after surgery. The lobectomy group had a higher variation of FEV1[(0.34±0.49)L vs.(0.18±0.26)L, P=0.006] and change rate of FVC(%)[9.28(2.15, 18.94) vs. 5.24(0.52, 11.45), P=0.0032] and FEV1(%)[10.45(3.15, 21.32) vs. 6.50(1.55, 14.24), P<0.001] in the first year after surgery. However, the variation of FVC[(0.29±0.36)L vs.(0.21±0.24)L, P=0.176) and the change rate of DLCO(%)[8.35(2.15, 16.45) vs. 6.23(2.12, 14.54), P=0.143] didn't show a significant difference between the two groups. Conclusion:Whether in the short or the middle postoperative period, segmentectomy can preserve postoperative respiratory function than lobectomy.

目的 评估胸腺瘤WHO分型、Masaoka分期与其预后的相关性.方法 纳入2009～2019年在复旦大学附属华山医院接受手术治疗的胸腺瘤患者468例,其中男234例、女234例,年龄21～83 (49.6±18.7)岁.行胸腔镜手术132例,胸骨正中切口手术336例,平均随访时间(5.7±2.8)年.分析患者的临床资料.结果 胸骨正中切口组术中出血量(178.3±133.5)mL,胸腔镜手术组术中出血量(164.8±184.1)mL,差异无统计学意义(P=0.537).胸骨正中切口组手术时间(3.3±0.7)h,胸腔镜组手术时间(3.4±1.2)h,差异无统计学意义(P=0.376).术后活动性出血、膈神经损伤、乳糜胸并发症在胸腔镜组分别为8例、9例、1例,在胸骨正中切口组分别为37例、31例、7例,差异均无统计学意义(P=0.102,0.402,0.320).WHO病理分型A型、AB型、B1型、B2型、B3型和C型胸腺瘤患者5年累计无进展生存率分别为100.0％、100.0％、95.7％、81.4％、67.5％和50.0％ (P＜0.001).Masaoka Ⅰ～Ⅳ期胸腺瘤患者5年累计无进展生存率分别为96.1％、89.2％、68.6％和19.3％ (P＜0.001).伴重症肌无力患者5年累计无进展生存率为87.3％,无重症肌无力患者为78.2％ (P＜0.001).胸腔镜与胸骨正中切口患者5年累计无进展生存率分别为82.4％和83.8％ (P=0.904).结论 WHO病理分型与Masaoka分期对临床预后有提示意义.伴重症肌无力胸腺瘤患者预后较好,提示早诊断和早治疗对胸腺瘤具有重要意义.

2019年12月以来,湖北省武汉市陆续出现2019新型冠状病毒（2019-nCoV,SARS-CoV-2）感染病例,疫情持续蔓延,全国其他地区也相继发现了此类病例。新型冠状病毒肺炎疫情给胸外科临床实践带来了巨大挑战。门诊需要加强对磨玻璃影及肺内斑块影病例的鉴别诊断。疫情期间严格控制手术指征,推迟择期手术;拟行限期手术患者,需隔离2周且核酸检测阴性后,方可开展手术;在疫区拟行急诊手术患者,术前应注意排查是否合并新型冠状病毒感染,必要时行核酸检测;拟行急诊手术患者,必要时术前应开展核酸检测,术中按三级防护处理。严格开展手术消毒隔离措施。在术后患者中,积极排查合并新型冠状病毒感染患者。在新型冠状病毒感染患者抢救过程中,需要注意预防、治疗相关并发症,包括机械通气相关性气胸或纵隔气肿以及气管插管后损伤。

目的 探讨miR-138介导ERK和AKT对非小细胞肺癌(NSCLC)细胞株A549增殖和迁移的作用机制.方法 选取NSCLC细胞株A549分成Az组、Am组和Ay组,Az组A549细胞转染空载体,Am组转染miR-138-mimics,Ay组转染miR-138-inhibitions,采用RT-PCR法检测miR-138、ERK和AKT mRNA水平变化,Westernblot法检测ERK和AKT蛋白,分别用Transwell法和MTT法检测A459细胞的迁移和增殖情况,流式细胞仪检测A549细胞凋亡程度.结果 RT-PCR检测三组miR-138、ERK和AKT mRNA水平变化:Ay组ERK和AKT mRNA水平变化最高,Az组其次,Am组最低;Am组miR-138水平变化最高,Az组其次,Ay组最低(均P＜0.05).Westernblot法检测三组ERK和AKT蛋白表达:Ay组ERK和AKT蛋白表达最高,Az组其次,Am组最低(均P＜0.05).流式细胞仪检测三组A549细胞凋亡程度:Am组A549细胞凋亡最多,Az组其次,Ay组最低,Am组A549细胞凋亡数量较Ay组多,说明A549细胞凋亡随miR-138水平增加而上升(均P＜0.05).Transwell检测三组A549细胞迁移能力:Ay组癌细胞迁移能力强,显微镜下细胞数量多,Am组癌细胞数量较Az组少,迁移能力较弱(均P＜0.05).MTT检测三组A549细胞增殖能力:Ay组细胞增殖能力最高,Az组其次,Am组最弱(均P＜0.05).结论 miR-138在NSCLC细胞株A549的迁移和增殖中发挥重要作用,其过表达可调控ERK和AKT信号,抑制细胞迁移和增殖,促进细胞凋亡.

Objectives: Video assisted thoracoscopic surgery (VATS) can currently be used to diagnose and treat pulmonary nodules. However, intraoperative location of pulmonary nodules in VATS is challenging due to their small diameter and deep location in the pulmonary parenchyma. The purpose of this study was to report the clinical safety and effectiveness of CT-guided hook-wire for preoperative localization of malignant pulmonary nodules smaller than 1 cm in diameter.Methods: From February 2017 to January 2018, we collected the data of 80 patients with malignant pulmonary nodules less than 1 cm in diameter who underwent CT-guided hook-wire preoperative localization and VATS surgery. The effectiveness of preoperative localization was evaluated based on surgical duration, success rate of VATS surgery, and localization-related complications.Results: The diameter of pulmonary nodules were 0.85 ± 0.17 mm with a distance to the pleural surface of 19.66 ± 14.10 mm. The length of the hook-wire in the lung parenchyma was 29.17 ± 13.14 mm and hook-wire dislodgement occurred in 2 patients. Complications included 27 cases of minor pneumothorax and 18 cases of mild parenchymal hemorrhage. A significant correlation was observed between the length of the hook-wire in the lung parenchyma and mild parenchymal hemorrhage (P = 0.044). The average time of hook-wire localization was 9.0 ± 2.6 min and the average operation time for VATS was 89.02 ± 23.35 min without conversion thoracotomy.Conclusions: CT-guided hook-wire localization of the lesion during VATS resection is safe for malignant pulmonary nodules with diameter less than 1 cm.

目的 本研究旨在阐明内皮细胞特异性敲除TFPI对内毒素引起小鼠急性肺损伤的影响和可能机制.方法 采用气管内滴注内毒素建立急性肺损伤小鼠模型.与野生型小鼠比较,评价内皮细胞中的TFPI对急性肺损伤内皮细胞屏障功能和炎性反应的作用,评价内皮细胞敲除TFPI后对炎性信号通路NF-κB通路的影响.结果 内皮细胞敲除TFPI可以明显加重内毒素所引起急性肺损伤的肺部病理改变,增加肺泡灌洗液中蛋白含量及伊文思蓝的渗透,促进肺组织及肺泡灌洗液中炎性因子TNF-α、IL-1β和IL-6的分泌.内皮细胞敲除TFPI小鼠与野生型内毒素诱导的急性肺损伤小鼠比较,肺泡灌洗液及肺组织中炎性细胞浸润增加.研究发现内皮细胞TFPI敲除与野生型小鼠相比内毒素诱导后,其炎性信号通路NF-κB激活更加明显.以上研究结果证实内皮细胞TFPI敲除小鼠急性肺损伤后肺组织中的炎性反应和血管渗透性都明显增加.结论 特异性内皮细胞TFPI敲除小鼠,在内毒素诱导的急性肺损伤模型中,通过对NF-κB信号通路的激活来促进肺组织的炎性反应和血管内皮细胞的通透性.

BACKGROUND:Angiolymphatic invasion (ALI) plays an important role in lymph node metastasis. The presence of an ALI predicts a high risk for lymph node metastasis and a poor prognosis in patients with lymph node negative esophageal carcinoma. The independent prognostic value of ALI in node-negative patients remains controversial. A meta-analysis was conducted to investigate the relationship between ALI and prognosis in cases of lymph node negative esophageal carcinoma.METHODS:We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases for studies on the relationship between ALI and the prognosis of patients with esophageal carcinoma. Studies with N0 patients' survival data related to ALI were included. The effect size (ES) was the hazard ratio (HR) with 95% confidence intervals (CI) for cancer-specific survival (CSS), overall survival (OS) and recurrence-free survival (RFS).RESULTS:A total of 9 studies with 2,154 patients were included after applying the inclusion and exclusion criteria. The pooled HR showed that patients with ALI have a poor cancer specific survival (HR =2.54; 95% CI, 1.84-3.51; P<0.001), a poor overall survival (HR =2.84; 95% CI, 2.17-3.72; P<0.001) and a short disease free survival (HR =2.84; 95% CI: 1.85-4.37; P<0.001).CONCLUSIONS:ALI could be used as an indicator for identifying high-risk patients with lymph node-negative esophageal carcinoma and can be used as an indicator for sub-stages in further stage classification.

Lung cancer is the most frequent cancer type and is the leading cause of tumour-associated deaths worldwide. Nuclear cap-binding protein 1 (NCBP1) is necessary for capped RNA processing and intracellular localization. It has been reported that silencing of NCBP1 resulted in cell growth reduction in HeLa cells. Nevertheless, its clinical significance and underlying molecular mechanisms in non-small-cell lung cancer remain unclear. In this study, we found that NCBP1 was significantly overexpressed in lung cancer tissues and several lung cancer cell lines. Through knockdown and overexpression experiments, we showed that NCBP1 promoted lung cancer cell growth, wound healing ability, migration and epithelial-mesenchymal transition. Mechanistically, we found that cullin 4B (CUL4B) was a downstream target gene of NCBP1 in NSCLC. NCBP1 up-regulated CUL4B expression via interaction with nuclear cap-binding protein 3 (NCBP3). CUL4B silencing significantly reversed NCBP1-induced tumorigenesis in vitro. Based on these findings, we propose a model involving the NCBP1-NCBP3-CUL4B oncoprotein axis, providing novel insight into how CUL4B is activated and contributes to LUAD progression.

目的 探讨快速康复外科护理对胸腔镜肺段切除术患者术后恢复的影响.方法 于2016年1月—2017年1月,选取复旦大学附属华山医院胸外科拟行胸腔镜肺段切除手术的患者126例为研究对象,采用随机数表法将其分为观察组(n=63)和对照组(n=63).对照组采用传统的胸外科围手术期护理,观察组患者在围手术期给予快速康复外科护理,比较两组患者术后恢复指标、并发症发生率、术后7d的生存质量评分以及出院时患者对护理工作的满意度.结果 观察组术后胸腔引流管放置时间、首次排便时间、术后住院天数与并发症的总发生率低于对照组(P<0.05),观察组术后7 d生存质量量表的生理、心理、社会关系领域评分及总分均高于对照组(P<0.05),观察组护理工作满意度优于对照组(P<0.05).结论 快速康复外科护理对胸腔镜肺段切除术患者具有较好的意义,能促进术后康复,减少术后并发症的发生,提高术后生活质量,值得临床推广应用.

The pattern of lymph node metastasis and surgical method in superficial esophageal squamous cell carcinoma (sESCC) remains to be established. Clinical data of all patients from 2003 to 2015 who underwent curative esophagectomy for thoracic sESCC were collected based on a prospectively-maintained database. The pattern of lymph node metastasis was analyzed based on depth of tumor invasion and tumor location. The involved lymph node region was associated to the tumor location, however, upper mediastinal and perigastric region was the most vulnerable region. As for the depth of tumor invasion, the incidence of lymph node metastasis increased with the depth of tumor invasion going deeper. No lymph node involvement was found in tumors invading proper mucosa (M2), while the distribution of positive lymph nodes in tumors invading the deepest 1/3 submucosa was similar to that in advanced ESCC. Lymphatic invasion, tumor location and upper mediastinal lymph node involvement were independent predictors for cervical lymph node metastasis. For patients without lymphatic invasion, the positive predictive value of upper mediastinal lymph node metastasis for positive cervical lymph node was low (0∼25%), while the negative predictive value was very high, wherever the tumor located (93.8∼100%). Tumors invading till proper mucosa was the best indication for endoscopic mucosa resection; Tumors invading the deepest 1/3 submucosa might benefit from neoadjuvant therapy; Mediastinal-abdominal lymphadenectomy was essential for sESCC. For those without lymphatic invasion, cervical lymphadenectomy might be avoided in case of negative upper mediastinal lymph node. All authors have declared no conflicts of interest.

肺癌的发病率及死亡率在全球范围内越来越高,随着CT的普及,越来越多的早期肺癌能被及时发现和治疗.手术作为肺癌的主要治疗方式,胸腔镜下解剖性肺段切除术在非小细胞肺癌中的治疗作用正引起胸外科医生们的关注.在此,我们将讨论胸腔镜解剖性肺段切除术在治疗早期非小细胞肺癌中的应用.

The WNT/β-catenin signaling pathway plays a critical role in cellular proliferation, differentiation and organogenesis. Aberration activation of WNT/β-catenin pathway and dysregulation of miRNA related with this pathway are involved in oncogenesis and tumor progression in primary lung cancer. Understanding the mechanism of the WNT/β-catenin signaling pathway and illuminating the interaction between miRNA and the members of this pathway may improve the perspectives of using these molecules as potential therapeutic targets for primary lung cancer. This review focused on the participation of the WNT/β-catenin signaling pathway and miRNA in lung cancer and discussion of potential targets for this malignancy therapy in the future.

BACKGROUND:Lung cancer is the leading cause of cancer death worldwide. However, the molecular mechanisms underlying lung cancer development have not been fully understood. The functions of histone deacetylases (HDACs), a class of total eighteen proteins (HDAC1-11 and SIRT1-7 in mammals) that deacetylate histones and non-histone proteins, in cancers are largely unknown.METHODS:Hdac7 +/-/K-Ras mice and HDAC7-depleted human lung cancer cell lines were used as models for studying the function of Hdac7 gene in lung cancer. Kaplan-Meier survival analysis was performed to explore the relationship between HDAC7 expression and prognosis of human lung cancers. Recombinant lentivirus-mediated in vivo gene expression or knockdown, Western blotting, and pull-down assay were applied to investigate the underlying molecular mechanism by which Hdac7 promotes lung tumorigenesis.RESULTS:The number and burden of lung tumor were dramatically reduced in Hdac7 +/-/K-Ras mice compared to control K-Ras mice. Also, in Hdac7 +/-/K-Ras mice, cell proliferation was significantly inhibited and apoptosis in lung tumors was greatly enhanced. Similarly, cell proliferation and anchorage-independent growth of human lung cancer cell lines expressing shHDAC7 were also significantly suppressed and apoptosis was dramatically elevated respectively. Mechanistic study revealed that Hdac7 mutation in mouse lung tumors or HDAC7 depletion in human tumor cell lines resulted in significantly enhanced acetylation and tyrosine-phosphorylation of Stat3 and HDAC7 protein directly interacted with and deacetylateed STAT3. The Hdac7 mutant-mediated inhibitory effects on lung tumorigenesis in mice and cell proliferation/soft agar colony formation of human lung cancer cell lines were respectively reversed by expressing dnStat3. Finally, the high HDAC7 mRNA level was found to be correlated with poor prognosis of human lung cancer patients.CONCLUSION:Our study suggests that Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation via deacetylating Stat3 and may shed a light on the design of new therapeutic strategies for human lung cancer.

Circulating tumor cells (CTCs) are important markers of metastatic cancer. The isolation and detection of CTCs from peripheral blood provides valuable information for cancer diagnosis and precision medicine. However, cost-efficient targeted separation of CTCs of different origins with clinically significant specificity and efficiency remains a major challenge. In this study, a facile approach was developed to fabricate a thin sheet of hyaluronic acid (HA)-functionalized PLGA nanofibrous membrane and integrate it into a microfluidic chamber. The HA was covalently conjugated onto polyethyleneimine (PEI)-modified electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers. Different techniques were employed to characterize the resulted nanofibers. The results show that the CD44+ carcinoma of various origins (HeLa, KB, A549, and MCF-7 cells) could be selectively captured by the PLGA-PEI-HA nanofibers in the microfluidic platform. Importantly, the PLGA-PEI-HA nanofibrous membrane was more efficient to capture HeLa cancer cells under flowing conditions than in static dishes, and at a really low density (20 cells per mL). Furthermore, with constant media perfusion, the captured HeLa cells could grow on the nanofibrous membrane in the microchip for days without compromised cell viability. This is the first trial of using HA-functionalized electrospun nanofibers in a lab-chip device for cancer cell capture and culture. Compared to conventional CTC capture methods, the integration of inexpensive functional electrospun nanofibers and microfluidic technologies may expand the frontiers of using advanced nanomaterials in portable diagnostic applications.