Selection and Characterization of DNA Aptamers for Cytidine and Uridine.

Cytidine and uridine are two essential pyrimidine ribonucleotides, and accurate detection of these nucleosides holds significant biological importance. While many aptamers were reported to bind purines, little success was achieved for pyrimidine binding. This study employs the library-immobilization capture-SELEX technique to isolate aptamers capable of selectively binding to cytidine and uridine. First, a selection was performed using a mixture of cytidine and uridine as the target. This selection led to the isolation of a highly selective aptamer for cytidine with a dissociation constant (Kd ) of 0.9 µM as determined by isothermal titration calorimetry (ITC). In addition, a dual-recognition aptamer was also discovered, which exhibited selective binding to both cytidine and uridine. Subsequently, a separate selection was carried out using uridine as the sole target, and the resulting uridine aptamer displayed a Kd of 4 µM based on a thioflavin T fluorescence assay and a Kd of 102 µM based on ITC. These aptamers do not have a strict requirement of metal ions for binding, and they showed excellent selectivity since no binding was observed with their nucleobases or nucleotides. This study has resulted three aptamers for pyrimidines, which can be employed in biosensors and DNA switches.

Capture-SELEX of DNA Aptamers for Sulforhodamine B and Fluorescein.

While many dye binding aptamers have been reported, most of them were for light-up aptamers that can significantly enhance the quantum yield of fluorophores. Sulforhodamine B (SRhB) was used as a target previously to select both DNA and RNA aptamers, and the DNA aptamer was a G-quadruplex that can bind to a number of rhodamine analogs. In addition, the previous selections were performed by immobilizing the target molecules. In this work, the library immobilization method was used to respectively select aptamers for SRhB and fluorescein. The SRhB aptamer has a non-G-quadruplex structure with a Kd of 1.0 µM measured from isothermal titration calorimetry. Upon titration of the aptamer, the fluorescence of SRhB increased 2.5-fold, and this aptamer does not require Mg2+ for binding. Rhodamine B has even tighter binding suggesting binding through the xanthene moiety of the dyes. No binding was detected for fluorescein. For the fluorescein selection, a dominant aptamer sequence with a Kd of 147 µM was obtained. This study provides two new aptamers for two important fluorophores that can be used to study aptamer-based separation, dye detection and catalysis. Comparison of these aptamers also provides insights into the effect of functional groups on aptamer binding.

Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics.

Background: Glioblastoma (GBM), a prevalent malignant neoplasm within the neuro-oncological domain, has been a subject of considerable scrutiny. Macrophages, serving as the principal immunological constituents, profoundly infiltrate the microenvironment of GBM. However, investigations elucidating the intricate immunological mechanisms governing macrophage involvement in GBM at the single-cell level remain notably limited. Methods: We conducted a comprehensive investigation employing single-cell analysis, aiming to redefine the intricate cellular landscape within both the core and peripheral regions of GBM tumors. Our analytical focus extended to the profound study of macrophages, elucidating their roles within the context of oxidative stress, intercellular information exchange, and cellular trajectories concerning GBM and its assorted subpopulations. We pursued the identification of GBM prognostic genes intricately associated with macrophages. Utilizing experimental research to investigate the relevance of MANBA in the context of GBM. Results: Our investigations have illuminated the central role of macrophages in the intricate interplay among various subpopulations within the GBM microenvironment. Notably, we observed a pronounced intensity of oxidative stress responses within macrophages when compared to their GBM counterparts in other subpopulations. Moreover, macrophages orchestrated intricate cellular communication networks, facilitated by the SPP1-CD44 axis, both internally and with neighboring subpopulations. These findings collectively suggest the potential for macrophage polarization from an M1 to an M2 phenotype, contributing to immune suppression within the tumor microenvironment. Furthermore, our exploration unearthed GBM prognostic genes closely associated with macrophages, most notably MANBA and TCF12. Remarkably, MANBA appears to participate in the modulation of neuroimmune functionality by exerting inhibitory effects on M1-polarized macrophages, thereby fostering tumor progression. To bolster these assertions, experimental validations unequivocally affirmed the promotional impact of MANBA on GBM, elucidated through its capacity to curb cell proliferation, invasiveness, and metastatic potential. Conclusion: These revelations represent a pivotal step towards unraveling the intricate immunological mechanisms governing the interactions between macrophages and diverse subpopulations within the GBM milieu. Furthermore, they lay the foundation for the development of an innovative GBM prognostic model, with MANBA at its epicenter, and underscore the potential for novel immunotherapeutic targets in the ongoing pursuit of enhanced treatment modalities for this formidable malignancy.

Integrative pan-cancer analysis and clinical characterization of the N7-methylguanosine (m7G) RNA modification regulators in human cancers.

Background: RNA modification is one of the epigenetic mechanisms that regulates post-transcriptional gene expression, and abnormal RNA modifications have been reported to play important roles in tumorigenesis. N7-methylguanosine (m7G) is an essential modification at the 5' cap of human mRNA. However, a systematic and pan-cancer analysis of the clinical relevance of m7G related regulatory genes is still lacking. Methods: We used univariate Cox model and Kaplan-Meier analysis to generate the forest plot of OS, PFI, DSS and identified the correlation between the altered expression of m7G regulators and patient survival in 33 cancer types from the TCGA and GTEx databases. Then, the "estimate" R-package, ssGSEA and CIBERSORT were used to depict the pan-cancer immune landscape. Through Spearman's correlation test, we analyzed the correlation between m7G regulators and the tumor microenvironment (TME), immune subtype, and drug sensitivity of the tumors, which was further validated in NSCLC. We also assessed the changes in the expression of m7G related regulatory genes in NSCLC with regards to the genetic and transcriptional aspects and evaluated the correlation of METTL1 and WDR4 expression with TMB, MSI and immunotherapy in pan-cancer. Results: High expression of most of the m7G regulators was significantly associated with worse prognosis. Correlation analyses revealed that the expression of majority of the m7G regulators was correlated with tumor immune infiltration and tumor stem cell scores. Drug sensitivity analysis showed that the expression of CYFP1,2 was closely related to drug sensitivity for various anticancer agents (p < 0.001). Analysis of the pan-cancer immune subtype revealed significant differences in the expression of m7G regulators between different immune subtypes (p < 0.001). Additionally, the types and proportions of mutations in METTL1 and WDR4 and their relevance to immunotherapy were further described. Conclusion: Our study is the first to evaluate the correlation between the altered expression of m7G regulators and patient survival, the degree of immune infiltration, TME and drug sensitivity in pan-cancer datasets.

The difference of auxiliary examination parameters between margin recurrence and granuloma on enhanced computed tomography after sublobar resection.

Background: Imaging examinations following sublobar resection of lung cancer often find thickened neoplasms around the resection margin. Identifying whether the neoplasms are postoperative recurrence or margin granulomas is vitally important. However, the identification mainly depends on the empirical judgment of the imaging department or clinicians in each clinical center at present, and there are few relevant studies, so it is hard to formulate a relatively unified standard. Therefore, we collected data from patients with thickened neoplasms around the resection margin after sublobar resection and sought to discover how to differentiate granulomas from tumor recurrence. Methods: We examined the clinical records of 15 patients with neoplasms around the margins which identified as malignant in auxiliary examination reports, and received second surgery after first sublobar resection. We collected their postoperative pathology and auxiliary examination parameters. The univariate predictors helpful in distinguishing between recurrence and granuloma were analyzed as a diagnostic test. Results: Of the 15 patients with neoplasms around the resection margin, six were diagnosed with benign granulomas, and nine were diagnosed with primary lung cancer recurrence. The results revealed that age, gender, specific surgical method, maximum standardized fluorodeoxyglucose uptake value (SUVmax), and follow-up time were not significantly different, but there were significant differences in enhanced computed tomography (CT) values in several analyses, which calculated by the hospital imaging system. The maximum CT values of the tumor recurrence and granuloma were 104.9±8.051 and 130.3±7.017 (P=0.045), the minimum CT values (15.67±5.113 vs. -17.17±4.826, P=0.0007) and in the floating range CT values (148.00±5.471 vs. 88.11±7.671, P<0.0001), respectively. Conclusions: Differentiating between tumor recurrence and granulomas after sublobar resection remains difficult. However, examining the differences in enhanced CT allows the clinician to make an informed diagnosis that aids further investigation and treatment.

Novel Branched-Chain Amino Acid-Catabolism Related Gene Signature for Overall Survival Prediction of Pancreatic Carcinoma.

Branched-chain amino acid (BCAA) metabolism plays an important role in the pancreatic carcinogenesis, but its mechanism remains unclear. Hence, this study was performed to investigate the value of genes related to BCAA catabolism in pancreatic cancer. The online Gene Expression Omnibus database, The Cancer Genome Atlas, and International Cancer Genome Consortium data sets were searched for bioinformatic analysis. Univariate Cox and Lasso regression were applied to construct a predictive model. Human cancer cell lines and tissue microarray (TMA) were applied for validation. From the 48 BCAA-catabolism enzyme (BCE) genes, a 5-gene risk-score (ABAT, ACAT1, BCAT1, BCAT2, and DBT) was constructed. Patients in high-risk and low-risk groups stratified by risk-score indicated significantly different overall survival. Given the clinical parameters, the risk-score was an independent predictor for prognosis. Among the five genes, BCAT2 and ABAT were hub genes with favorable prognosis value, which was validated by TMA immunohistochemistry (IHC) staining. Immune infiltration analysis indicated high-risk group enriched macrophage, and decreased positive cell density of stromal CD68+ macrophage in TMA was observed for BCAT2 with low-expression versus high-expression cases. In conclusion, a risk-score involving five BCE genes was proposed to predict the poor prognosis of pancreatic cancer. On the basis of the immune infiltration analysis, the underlying mechanism might be BCAT2 associated stromal macrophage infiltration.

Comparison of clinical outcomes of conservative treatment and surgery for esophageal cancer patients who achieve a clinical complete response following neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

Background: Although the clinical complete response (cCR) for esophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) may be related to the good survival prognosis, the choice of conservative and surgical treatments is still controversial. This study sought to compare the clinical outcomes of these two treatments. Methods: A systematic search was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of the PubMed, Embase, and Cochrane Library databases to retrieve articles published between January 1, 2010 and March 31, 2022 on the efficacy of conservative treatment or surgery in esophageal cancer patients who had achieved a cCR after nCRT The predominant endpoints were overall survival (OS), disease-free-survival (DFS), local recurrence, and distant metastasis. Odds ratios (ORs) were generated for the dichotomous variants by meta-analysis. The software implemented was Stata 16.0 MP. This research was prospectively registered under PROSPERO (registration number: CRD42022332143). Results: Ultimately, eight retrospective cohort studies and one randomized controlled trial, comprising 749 patients (nCRT group: 333 and nCRT + surgery group: 416), were included in the meta-analysis after two researchers independently assessed the risk of bias for all included studies. The 2-year OS [OR =1.239, 95% confidence interval (CI): 0.891 to 1.723] and 5-year OS (OR =1.369, 95% CI: 0.963 to 1.947) were comparable between the nCRT group and nCRT plus surgery (nCRT + S) group. Patients in the nCRT + S group had significantly longer DFS (2 and 5 years, OR ranging from 0.303 to 0.357) and lower local recurrence rate (OR =0.179, 95% CI: 0.104 to 0.291) than those in the nCRT group. However, the distant metastasis rate was similar between the nCRT group and the nCRT + S group. Conclusions: Esophageal cancer patients who achieved a cCR after nCRT and received an esophagectomy had better DFS and lower local recurrence than those who received conservative treatment; however, this DFS advantage did not lead to a significant difference in OS. Salvage surgery may be a feasible option for resectable patients who have local recurrence after achieving cCR.

An improved method of anchoring chest drain and suture technique for Uni-portal VATS incision.

Uni-portal video-assisted thoracoscopic approach is currently a popular surgical technique in general thoracic surgery. After operation, a chest tube is usually placed through the incision to drain the effusion and gas from the thoracic cavity. In the conventional method, the retaining stitches should be taken out ten days after removing chest drain. To get better would-healing and avoid unsightly scar, we explored a method of anchoring chest drain and two-layer suture for Uni-portal incision without removing stitches post operation.

Identification of immune-associated lncRNAs as a prognostic marker for lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) accounts for the largest proportion of lung cancer patients and has the highest morbidity and mortality worldwide. Accumulating evidence shows that immune-associated long non-coding RNAs (lncRNAs) play a role in LUAD, although their predictive value for immunotherapy treatment and cancer-related death remains poorly investigated. METHODS: Gene expression profiles and clinical data were obtained from The Cancer Genome Atlas. We constructed a risk model by univariate and multivariate Cox regression and least absolute shrinkage and selection operator regression analysis and subsequently divided each sample into low- or high-risk category. Survival and receiver operating characteristic (ROC) analyses were applied to assess the prognostic value of the model. Additionally, immune and somatic mutation status were analysed between the two risk groups. Finally, the model was applied to pancreatic ductal adenocarcinoma (PDAC) samples to explore the applicability of the model in other cancers. RESULTS: We obtained data from 499 LUAD patients and randomised the samples into a training set (N=351) and validation set (N=148) at a 7:3 ratio. We detected 7 immune-associated lncRNAs (AP000695.2, AC026355.2, LINC01843, ITGB1-DT, LINC01150, AL590226.1 and AC091185.1) that were applicable for establishing a risk signature. Survival analysis revealed that patients categorised in the high-risk group had shorter overall survival (OS) than those in the low-risk group. ROC analyses showed excellent AUC values in all data sets (>0.65 at 1, 3, and 5 years). Notably, ESTIMATE algorithm and analysis of PCA, (ss)GSEA, and somatic mutations revealed that the high-risk group had a stronger immunosuppressive status and a higher tumour mutation burden (TMB). Moreover, patients in the low-risk group responded better to immunotherapy due to higher levels of immune-checkpoint receptor genes and TLS-related genes. Our model using the 7 immune-associated lncRNAs showed similar applicability for PDAC patients. CONCLUSIONS: We constructed a model for risk signatures based on 7 immune-associated lncRNAs and showed its prognostic value for identifying immune and somatic mutation characteristics in LUAD patients, which may assist clinical treatment plans and elucidate molecular mechanisms of LUAD immunity.

Information-Aware Secure Routing in Wireless Sensor Networks.

Secure routing is crucial for wireless sensor networks (WSNs) because they are vulnerable to various attacks. In this paper, we propose a new secure routing protocol for WSNs in the presence of malicious nodes. For each relay node in the route, associated information such as its trust value and status is considered in the protocol. The trust value is defined as the attack probability of the node according to previous packet-forwarding behaviors, and the status is a hybrid metric that combines the residual energy and distance to the sink node. Therefore, the route generated by the protocol is secure against malicious attacks and globally optimal according to the associated information. We used an improved variant of the Dijkstra algorithm to generate the secure route for WSNs in the presence of malicious nodes. Compared with the Reputation-Based Mechanism to Stimulate Cooperation (RBMSC) model in the same simulation environment, the proposed model can maintain a higher delivery ratio, which verifies the effectiveness of the proposed model on the basis of global optimization. Furthermore, compared with the traditional Dijkstra algorithm, the packet loss ratio in the improved Dijkstra algorithm is lower because it can more effectively avoid malicious nodes, thus verifying the effectiveness of the improved algorithm.

Prognosis of limited resection versus lobectomy in elderly patients with invasive lung adenocarcinoma with tumor size less than or equal to 2 cm.

BACKGROUND: This study aimed to evaluate the prognostic difference between limited resection and lobectomy among elderly patients with small size lung adenocarcinoma. METHODS: A total of 666 patients >65 years old with stage I lung adenocarcinoma and tumor size ≤2 cm were included. The patient survival was evaluated by disease-free survival (DFS) and overall survival (OS). Results: No DFS or OS advantage was found between the lobectomy and wedge resection groups when tumor sizes were ≤1 cm (DFS, P=0.112; OS, P=0.294). The wedge resection group had a significantly worse OS (P=0.041) than that in the lobectomy group when tumor sizes were >1 cm and ≤2 cm. CONCLUSIONS: We conclude that wedge resection may be a reasonable surgical choice for elderly patients with tumor sizes ≤1 cm.

Appropriate lymphadenectomy significantly reduced recurrence after segmentectomy for patients with non-small cell lung cancer.

BACKGROUND: Segmentectomy has been widely used for small-sized non-small cell lung cancer (NSCLC). The objective of this study is to determine the impact of number of harvested lymph nodes (LNs) on survival for patients undergoing segmentectomy. METHODS: The clinicopathologic data of patients undergoing segmentectomy for NSCLC from July 2011 to December 2014 were retrospectively analyzed. Survival analysis was performed by Kaplan-Meier method and Cox regression analysis. RESULTS: A total of 259 patients with NSCLC were eligible for analysis. Patients with harvested LN ≥6 had higher frequency of nodal metastasis in pathologic examination (9.4% vs. 1.5%, P=0.005). The 3-year recurrence-free survival (RFS) of patients with harvested LN ≥6 (90.2%) was significantly higher than that of patients with harvested LN <6 (73.7%, log-rank P=0.038). Multivariable Cox analysis identified harvested LN ≥6 as an independent predictor for improved RFS [hazard ratio (HR) =0.35; 95% confidence interval (CI): 0.14-0.90; P=0.029]. There was no significant difference in RFS between patients with harvested LN station ≥3 and <3 (log-rank P=0.34). CONCLUSIONS: The number of harvest LN ≥6 was independently associated with improved RFS for NSCLC patients undergoing segmentectomy, supporting the National Comprehensive Cancer Network (NCCN) guidelines of appropriate LN sampling.

Predictors of recurrence and survival of pathological T1N0M0 invasive adenocarcinoma following lobectomy.

BACKGROUND: This retrospective research was designed to investigate the relationship between pT1N0M0 invasive adenocarcinoma (IADC) harboring solid (SOL) and/or micropapillary (MIP) components and its prognosis following lobectomy. METHODS: Clinical data of pT1N0M0 IADC patients were retrospectively collected from Shanghai Chest Hospital. Survival curves were plotted by Kaplan-Meier methods. Multivariable cox regressions were conducted to discover the independent risk factors of recurrence-free survival (RFS) and overall survival (OS), through which nomograms were performed to visualize the risk of recurrences and outcomes in personalized information. RESULTS: Totally, 1965 patients were enrolled, including 248 harboring SOL/MIP and 1717 not. IADC demonstrated worse 5-year RFS (81.9 vs. 92.2%, p < 0.001) and OS (85.7 vs. 94.4%, p < 0.001) when harboring SOL and/or MIP components. And this status became an independent factor associated with poorer RFS (HR 2.445, 95% CI 1.565-3.821, p < 0.001) and OS (HR 2.139, 95% CI 1.180-3.878, p = 0.012) instead of novel classification of IADC predominant patterns. No difference existed between SOL/MIP predominant and minor patterns. In addition, age > 60, smoking, post-chemotherapy and T1b were all indicating poorer RFS and smoking was also related with worse OS. The c-indexes of nomograms were 0.723 for RFS (95% CI, 0.662-0.784) and 0.703 for OS (95% CI, 0.629-0.777) respectively. CONCLUSIONS: Once the pT1N0M0 IADC harboring SOL/MIP, it strongly indicated the worse clinical recurrence and survival outcome, no matter whether the SOL and/or MIP was predominant. Smoking was correlated with worse prognosis for those patients. Age > 60 and stage T1b also indicated poorer RFS. Whether post-chemotherapy was harmful to pT1N0M0 IADC patients needed further research.

Impact of Solid Minor Histologic Subtype in Postsurgical Prognosis of Stage I Lung Adenocarcinoma.

BACKGROUND: Few studies focus on the outcome and effect of a postsurgical treatment strategy for early stage patients with minor solid components pattern. This study investigated the prognosis and the adjuvant chemotherapy benefit among stage I invasive lung adenocarcinoma patients with minor solid components pattern according to the eighth TNM staging classification. METHODS: A total of 3,308 lung adenocarcinoma patients with mixed histologic components was divided into three groups: solid predominant, solid minor, and solid absent pattern. Disease-free survival and overall survival were analyzed to evaluate survival difference among patients in the different groups using the Kaplan-Meier approach and multivariable Cox models. RESULTS: Both solid predominant and solid minor groups showed significantly worse disease-free survival (p < 0.001) and overall survival (p < 0.001) compared with the solid absent group. There were no significant disease-free survival (hazard ratio [HR] 1.41, 95% confidence interval [CI]: 0.87 to 2.30, p = 0.161) or overall survival (HR 1.60, 95% CI: 0.83 to 3.09, p = 0.159) difference between the former two groups. For patients in stage IB, adjuvant chemotherapy improves disease-free survival (HR 0.33, 95% CI: 0.11 to 1.02, p = 0.044) but not overall survival (HR 0.61, 95% CI: 0.21 to 1.77, p = 0.360) in the solid predominant group. No adjuvant chemotherapy benefits for disease-free survival (HR 1.04, 95% CI: 0.49 to 2.22; p = 0.922) and overall survival (HR 0.49, 95% CI: 0.13 to 1.90; p = 0.291) were seen for the solid minor group. CONCLUSIONS: Solid minor components predict a significantly worse prognosis compared with the solid absent pattern. However, adjuvant chemotherapy may be unhelpful to improve outcomes for stage IB patients with solid minor components after surgery.

Visceral pleural invasion predict a poor survival among lung adenocarcinoma patients with tumor size ≤ 3cm.

INTRODUCTION: The impact of visceral pleural invasion (VPI) on survival remains controversial for patients with early stage non-small cell lung cancer (NSCLC). This study investigated the survival status of VPI among patients with lymph node-negative lung invasive adenocarcinoma smaller than 3cm. METHODS: We retrospectively reviewed 2537 consecutive patients with pathologic stage I lung invasive adenocarcinoma. All patients had received lobectomy and system lymph nodes resection. Patients were classified into 4 groups according to tumor size and visceral pleural invasion status. Disease-free survival (DFS) and overall survival (OS) were analyzed to evaluate survival difference between these groups. RESULTS: 548 patients with VPI while 1989 patients without VPI were included in this study. For patients with tumor size ≤2cm, patients with VPI had significant worse DFS (HR,4.85; 95% CI, 2.98-7.91; p = .000) and OS(HR,3.52; 95% CI, 1.59-7.78; p = .002) compared with non-VPI group. For patients with tumor size between 2-3cm, patients with VPI had significant worse DFS (HR, 1.72; 95% CI, 1.16-2.55; p = .006) but no significant OS (HR, 1.31; 95% CI, 0.76-2.24; p = .330) compared with non-VPI group. For patients with VPI, there were no survival difference between tumor size 2-3cm group and ≤2cm group for both DFS(HR,1.02; 95% CI, 0.65-1.61; p = .939) and OS(HR,1.45; 95% CI, 0.71-2.97; p = .315). CONCLUSIONS: VPI could predict a poor survival even for node-negative invasive lung adenocarcinoma patients with tumor size less than 3cm.

Comprehensive study of prognostic risk factors of patients underwent pneumonectomy.

Introduction: To investigate postoperative complications and the prognostic risk factors of patients underwent pneumonectomy. Methods: Four hundred and six patients underwent pneumonectomy were subjected to the study. All the clinicopathologic data including age, gender, smoking history, surgical treatment, postoperative complications, tumor staging and the follow-up information were investigated. Results: The 30-day and 90-day mortality rates were 3.2% and 6.2%, respectively. Postoperative complications developed in 149 patients (36.7%), mainly included arrhythmia, transfusion, pulmonary infection, bronchopleural fistula and acute respiratory distress syndrome. During the follow-up, 189 patients experienced a relapse, consisting of 51 patients with local recurrence and 138 with distant recurrence. The median survival time was 24.4 months and the overall 1-year, 3-year and 5-year survival rates were 82.7%, 50.9% and 32.5%, respectively. Moreover, the overall 1-year, 3-year, 5-year survival rates for patients with non-small cell lung cancer (NSCLC) were 84.1%, 52.1% and 32.5%, respectively and patients with small cell lung cancer (SCLC) were 56.1%, 38.5% and 28.8%, respectively. Among NSCLCs, adenocarcinomas had a worse prognosis than squamous carcinomas. Compared to right pneumonectomy, patients with left pneumonectomy had a better prognosis. Multivariable analysis revealed ICU stay, disease stage, nodal stage and adjuvant chemotherapy were all significant predictors of overall survival (OS). Conclusions: Pneumonectomy is still a valuable and effective treatment option for patients with advanced lung cancer. Surgeons should be more cautious when patients had higher disease stage, adenocarcinoma and right-side lung cancer. Neoadjuvant chemotherapy did not affect the prognosis. Pneumonectomy could also achieve acceptable survival outcomes in well-selected SCLC patients.

The indication of completion lobectomy for lung adenocarcinoma ≤3 cm after wedge resection during surgical operation.

PURPOSE: This retrospective study was designed to find out the potential indications of completion lobectomy (CL) during wedge resection (WR) operation among patients with lung adenocarcinoma (ADC) ≤3 cm, by the use of Shanghai Chest Hospital Lung Cancer Database. PATIENTS AND METHODS: There were totally 1938 patients in this study, including 746 WRs and 1192 CLs. The propensity score matching (PSM) was performed to minimize the effect of confounders. Univariable and multivariable cox regressions were analyzed to discover the independent risk factors of recurrence-free survival (RFS) and overall survival (OS). Subgroup analysis and Kaplan-Meier survival curves were performed if necessary. RESULTS: The 5-year RFS (86.1 vs 91.5%, p = 0.001 for unmatched group; 84 v 92%, p < 0.001 for PSM group) and OS (83.6 vs 91.7%, p < 0.001 for unmatched group; 81.6 vs 88.2%, p < 0.001 for PSM group) all indicated a better prognosis when conducting CL. Subgroup analysis suggested that WR was appropriate for non-invasive ADC. Three prognostic factors (sex, surgical approach and pleural invasion) were correlated with RFS and two (sex and surgical approach) corresponded with OS in invasive ADC through multivariable analysis. Non-lepidic-predominant component showed a better RFS and OS when CL was operated after WR in the subgroup of invasive ADC. CONCLUSION: CL was an appropriate remediation to WR when the existence of invasive ADC, especially non-lepidic-predominant one. While WR could be applied if non-invasive ADC was confirmed. Whether lepidic-predominant adenocarcinoma was fit for WR needed further study.

Mitochondrial toxicity of perfluorooctane sulfonate in mouse embryonic stem cell-derived cardiomyocytes.

Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes. The cardiomyogenesis from ES cells in vitro was inhibited, and the expression of L-type Ca2+ channel (LTCC) was decreased to interrupt [Ca2+]c transient amplitude in cardiomyocytes after PFOS treatment. Transmission electron microscope revealed that swollen mitochondrion with vacuole in PFOS-treated cells. Meanwhile, mitochondrial transmembrane potential (ΔΨm) was declined and ATP production was lowered. These changes were related to the increased EGFR phosphorylation, activated Rictor signaling, then mediated HK2 binding to mitochondrial membrane. Furthermore, PFOS reduced the interaction of IP3R-Grp75-VDAC and accumulated intracellular fatty acids by activating Rictor, thereby attenuating PGC-1α and Mfn2 expressions, then destroying mitochondria-associated endoplasmic reticulum membrane (MAM), which resulted in the decrease of [Ca2+]mito transient amplitude triggered by ATP. In conclusion, mitochondrial structure damages and abnormal Ca2+ shuttle were the important aspects in PFOS-induced cardiomyocytes toxicity from ES cells by activating Rictor signaling pathway.

Predicting the recurrence risk factors and clinical outcomes of peripheral pulmonary adenocarcinoma ≤3 cm with wedge resection.

PURPOSE: This study was designed to investigate the risk factors of recurrence and survival of clinical stage I lung adenocarcinoma underwent wedge resection by the use of Shanghai Chest Hospital Lung Cancer Database. PATIENTS AND METHODS: A total of 746 patients with clinical stage I adenocarcinoma underwent wedge resection from 2010 to 2015 in our database were included in this study. Univariable and multivariable Cox proportional hazards regression were performed successively to select significant risk factors and then nomograms as well as the concordance indexes for RFS, OS and LCSS were developed, respectively. Kaplan-Meier survival curves were performed if necessary, with the identification of log-rank test. RESULTS: The 5-year RFS, OS and LCSS of clinical stage I adenocarcinoma underwent wedge resection were 86.1, 83.6 and 85.2%, respectively. There were three independent risk factors related with RFS (sex, pathology, pleural invasion), two related with OS (sex, volume ratio) and two with LCSS (sex, volume ratio) with the analysis of Cox regression and were selected to develop nomograms. The C-indexes of RFS, OS and LCSS were 0.767 (95% CI 0.667-0.867), 0.782 (95% CI 0.660-0.904) and 0.794 (95% CI 0.669-0.919), respectively. Lymphadenectomy did not show differences statistically but had tendencies of better RFS, OS and LCSS among the subgroup of invasive adenocarcinoma. CONCLUSION: Sex, pathology and pleural invasion could be recommended as criteria for clinical stage I adenocarcinoma undergoing wedge resection. And the larger the wedge volume and/or the smaller the tumor volume was, the better OS and LCSS were. If the volume ratio reached 10:1 or more, the survival rate was approximately 90% for both OS and LCSS. Whether lymphadenectomy was necessary for WR, especially in invasive adenocarcinoma, needed further research.

Solid predominant histologic subtype and early recurrence predict poor postrecurrence survival in patients with stage I lung adenocarcinoma.

INTRODUCTION: This study investigated the correlation between histologic predominant pattern and postrecurrence survival (PRS), and identified the clinicopathologic factors influencing PRS in patients with completely resected stage I lung adenocarcinoma. METHODS: A total of 136 stage I lung adenocarcinoma patients who experienced tumor recurrence after completely resection were included in this study. To analysis the association between histologic predominant pattern and PRS, invasive adenocarcinomas with mixed histologic components were divided into 2 groups: solid and nonsolid group (including lepidic, acinar, papillary, micropapillary) based on the histologic predominant pattern. PRS was analyzed to identify the prognostic predictors using the Kaplan-Meier approach and multivariable Cox models. RESULTS: For all stage I invasive adenocarcinoma patients, the majority of postsurgical recurrences occurred within 2 years. Patients with solid predominant histological pattern were associated with unfavorable PRS (HR, 2.40; 95%CI 1.13-5.08, p=.022). There was a significant difference for poor PRS for patients who diagnosed tumor recurrence shorter than 12 months after surgery (HR, 2.34; 95%CI 1.12-4.90, p=.024). Extrathoracic metastasis was associated with poor media PRS in univariable analysis (p =.011), however, there was no significant PRS difference in multivariable analysis (HR, 1.56; 95%CI 0.65-3.73, p=.322) compared with intrathoracic metastasis. CONCLUSIONS: Solid predominant histologic subtype and recurrence free interval less than 12 months predict worse PRS in patients with stage I lung adenocarcinoma.