Mesenchymal stem cell-derived small extracellular vesicles enhance the therapeutic effect of retinal progenitor cells in retinal degenerative disease rats.

Our previous study demonstrated that combined transplantation of bone marrow-derived mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone. Bone marrow- derived mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles. Small extracellular vesicles derived from bone marrow-derived mesenchymal stem cells, which offer low immunogenicity, minimal tumorigenic risk, and ease of transportation, have been utilized in the treatment of various neurological diseases. These vesicles exhibit various activities, including anti-inflammatory actions, promotion of tissue repair, and immune regulation. Therefore, novel strategies using human retinal progenitor cells combined with BMSC-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration. In this study, we developed such an approach utilizing retinal progenitor cells combined with bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats, a genetic model of retinal degeneration. Our findings revealed that the combination of bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats. The addition of bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival, migration, and differentiation of the exogenous retinal progenitor cells. Concurrently, these small extracellular vesicles inhibited the activation of regional microglia, promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina, and facilitated their differentiation into photoreceptors and bipolar cells. These findings suggest that bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.

Sublobar resection for lung adenocarcinoma less than 2 cm containing solid or micropapillary components radiologically presented as consolidation-to-tumor ratio (CTR) ≤0.25 [ground-glass opacity (GGO)].

Background: The suitability of sublobar resection as a surgical approach for early-stage non-small cell lung cancer (NSCLC) remains unclear. This study investigated the feasibility of sublobar resection in patients with pathological-stage IA adenocarcinoma less than 2 cm characterized by a high-risk pathological subtype but exhibiting radiologically noninvasive features. Methods: We conducted a retrospective review of patients diagnosed with pathological stage IA lung adenocarcinoma who underwent surgical intervention between 2013 and 2017. The inclusion criteria included a maximum tumor diameter of 2.0 cm or less, a consolidation-to-tumor ratio (CTR) of 0.25 or less, and a histopathological confirmation of a solid or micropapillary component. Patients were categorized into sublobar resection and lobectomy groups, and propensity score matching was employed to mitigate potential confounders. The primary endpoints were lung cancer-specific survival (LCSS) and overall survival (OS). Results: The study comprised 149 patients, with 84 in the lobectomy group and 65 in the limited resection group. In the overall cohort, the 5-year LCSS was 100% for both groups, while the 5-year OS was 97.6% (95% CI: 94.41-100.00%) in the lobectomy group and 100% in the sublobar resection group (P=0.21). After propensity score matching, the LCSS remained at 100% for both groups, and the 5-year OS was 97.14% in the lobectomy group and 100% in the sublobar resection group (P=0.32). Conclusions: Based on our experience, for lung adenocarcinoma containing solid/micropapillary subtype, a size less than 2 cm, and a CTR ≤0.25, the oncological outcomes appeared to be comparable between sublobar resection and lobectomy, suggesting that sublobar resection might serve as an equivalent alternative to lobectomy for such lesions.

Highly stereoselective α-glycosylation with GalN3 donors enabled collective synthesis of mucin-related tumor associated carbohydrate antigens.

Mucin-related tumor-associated carbohydrate antigens (TACAs) are important and interesting targets for cancer vaccine therapy. However, efficient access to a library of mucin-related TACAs remains a challenging task. One of the key issues is the challenging construction of α-GalNAc linkages. Here, we report highly stereoselective α-glycosylation with GalN3N-phenyl trifluoroacetimidate donors, which features excellent yields, outstanding stereoselectivities, broad substrate scope and mild reaction conditions. This method is successfully applied to highly stereoselective synthesis of GalN3-α-O-Ser, which served as the common intermediate for collective synthesis of a wide range of TACAs including TN antigen, STN antigen, 2,6 STF antigen, 2,3 STF antigen, glycophorin and cores 1-8 mucin-type O-glycans. In particular, the rationale for this highly stereoselective α-glycosylation is provided for the first time using DFT calculations and mechanistic studies, highlighting the crucial roles of reagent combinations (TMSI and Ph3PO) and the H-bonding directing effect of the N3 group.

Anti-Shedding Nickel-Protection-Layer Boosting an Ultrahigh Loading Carbon Fiber@Co-NiSx Electrode to Deliver Superior Areal/Volumetric/Gravimetric Capacitance.

Challenges remain to show good capacitive performance while achieving high loadings of active materials for supercapacitors. Trying to realize this version, a nickel-protecting carbon fiber paper@Co-doped NiSx (Ni-CP@Co-NiSx) electrode with high specific gravimetric, areal, and volumetric capacitance is reported in this work. This free-standing electrode is prepared by an electroplating-hydrothermal-electroplating (EHE) three-step method to achieve a high loading of almost 26.7 mg cm-2. The cobalt-doping and nickel-protection strategies effectively decrease the impedance and inhibit the active material dropping from the electrode resulting from the expansion stress, which endows the Ni-CP@Co-NiSx electrode with a high rate and good cycling performance, especially with an ultrahigh specific areal/volumetric/gravimetric capacitance of 53.3 F cm-2/2807 F cm-3/1997 F g-1 at 5 mA cm-2, respectively. Employing activated carbon functionalized with riboflavin (AC/VB2) as a negative electrode, the asymmetric supercapacitor device delivers a very high energy density of up to 60.4 W h kg-1. This work demonstrates that electrodes with a high loading density and excellent performance can be obtained by the combination of the EHE method to adjust the internal conductivity and external structural stability.

Tracheal tunica adventitia invasion after lobectomy in patients with non-small cell lung cancer.

BACKGROUND: For patients with non-small cell lung cancer, a negative margin status is required for radical pulmonary surgery. Residual disease of the margin has been thoroughly studied in the past few decades. However, the prognostic significance of tracheal tunica adventitia invasion after lobectomy remains unclear. In this study, we aimed to investigate the clinical influence of tracheal tunica adventitia invasion after lobectomy. METHODS: We retrospectively collected the clinical data of 591 patients who consecutively underwent pulmonary lobectomy, including sleeve lobectomy, between 2012 and 2018 at Shanghai Chest Hospital. According to the tracheal tunica adventitia invasion status, we allocated the patients into 2 groups (tracheal tunica adventitia invasion and non-tracheal tunica adventitia). Disease-free and overall survival were evaluated, and we discussed the necessity of radiotherapy in patients with tracheal tunica adventitia. RESULTS: After propensity score matching to balance baseline characteristics, there were 167 individuals in the tracheal tunica adventitia invasion and non-tracheal tunica adventitia groups. In the hazard analysis, we found that tracheal tunica adventitia increased the risk of recurrence (hazard ratio: 0.652; P = .002) and impaired long-term survival (P < .001). Subgroup analysis revealed that tracheal tunica adventitia was an important risk factor, especially when the hilar lymph nodes were positive. In addition, tracheal tunica adventitia invasion promoted extra-thoracic lymph node metastasis. We discovered that radiotherapy did not improve the prognosis of patients in the tracheal tunica adventitia invasion group. CONCLUSIONS: After lobectomy, tracheal tunica adventitia invasion is a risk factor for non-small cell lung cancer and potentially increases extra-thoracic lymph node metastasis. Moreover, tracheal tunica adventitia invasion is not sensitive to postoperative radiotherapy.

The consideration of surgery on primary lesion of advanced non-small cell lung cancer.

BACKGROUND: Numerous reports have shown that medical treatment confers excellent survival benefits to patients with advanced stage IV non-small cell lung cancer (NSCLC). However, the implications of surgery for primary lesions as palliative treatment remain inconclusive. METHODS: We retrospectively extracted clinical data from the Surveillance, Epidemiology, and End Results Program (SEER) database and selected patients with stage IV NSCLC. Patients were classified into non-surgery and surgery groups, and propensity score matching (PSM) analysis was performed to balance the baseline information. Patients in the surgery group, whose overall survival (OS) was longer than the median survival time of those in the non-surgery group, were deemed to benefit from surgery. We evaluated the efficacy of three surgical techniques, namely, local destruction, sub-lobectomy, and lobectomy, on the primary site in the beneficial population. RESULTS: The results of Cox regression analyses revealed that surgery was an independent risk factor for both OS (hazard ratio [HR]: 0.441; confidence interval [CI]: 0.426-0.456; P < 0.001) and cancer-specific survival (CSS) (HR: 0397; CI: 0.380-0.414; P < 0.001). Notably, patients who underwent surgery had a better prognosis than those who did not (OS: P < 0.001; CSS: P < 0.001). Moreover, local destruction and sub-lobectomy significantly compromised survival compared to lobectomy in the beneficial group (P < 0.001). After PSM, patients with stage IV disease who underwent lobectomy needed routine mediastinal lymph node clearing (OS: P = 0.0038; CSS: P = 0.039). CONCLUSION: Based on these findings, we recommend that patients with stage IV NSCLC undergo palliative surgery for the primary site and that lobectomy plus lymph node resection should be conventionally performed on those who can tolerate the surgery.

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Analysis for discharge within 2 days after thoracoscopic anatomic lung cancer surgery.

OBJECTIVES: The risk and beneficial factors of early discharge after thoracoscopic anatomic lung cancer surgery are unknown, and this study aims to investigate predictors and associated 30-day readmission for early discharge. METHODS: We performed a single-center retrospective analysis of 10,834 consecutive patients who underwent thoracoscopic anatomic lung cancer surgery. Two groups were determined based on discharge date: "discharged by postoperative Day 2" and "discharged after postoperative Day 2." Univariable and multivariable analysis were conducted to identify predictors for discharge. Using propensity score matching (PSM) to compare 30-day readmission rate between two cohorts. RESULTS: A total of 1911 patients were discharged by postoperative Day 2. Multivariable analysis identified older age (odds ratio (OR) = 1.014, p < 0.001), male sex (OR = 1.183, p = 0.003), larger tumor size (OR = 1.248, p < 0.001), pleural adhesions (OR = 1.638, p = 0.043), lymph nodes calcification (OR = 1.443, p = 0.009), advanced clinical T stage (vs. T < 2, OR = 1.470, p = 0.010), lobectomy resection (vs. segmentectomy resection, OR = 2.145, p < 0.001) and prolonged operative time (OR = 1.011, p < 0.001) as independent risk factors for discharge after postoperative Day 2. Three adjustable variables including higher FEV1 /FVC (OR = 0.989, p = 0.001), general anesthesia (GA) plus thoracic paravertebral blockade (vs. GA alone, OR = 0.823, p = 0.006) and uni-portal thoracoscopic surgery (vs. multi-portal, OR = 0.349, p < 0.001) were associated with a decreased likelihood of discharge after postoperative Day 2. Before and after a 1:1 PSM, discharged by postoperative Day 2 did not increase the risk of 30-day readmission compared to counterparts. CONCLUSIONS: Carefully selected patients can be safely discharged within 2 days after thoracoscopic anatomic lung cancer surgery. Three modifiable variables may be favorable for promoting discharge by postoperative Day 2.

The location of visceral pleural invasion in stage IB patients with non-small cell lung cancer: Comparison and prognosis.

OBJECTIVES: Recently, early-stage lung cancer has been drawing more attention, especially in screening and treatment. Visceral pleural invasion in stage IB cancer is considered as risk factor for poor prognosis. Herein, we aimed to study the distinction between the different locations of visceral pleural invasion. METHODS: In this retrospective cohort study, we summarized 58,242 patient cases that underwent surgery from 2015 to 2018 at Shanghai Chest Hospital. Of those patients, 389 met the inclusion criteria. Patients with PL3 pleural invasion were excluded. The patients were dichotomized into the interlobar pleural and peripheral pleural groups. The outcomes measured were overall survival (OS) and recurrence-free survival (RFS) rates. RESULTS: According to the initial analysis, the baseline characteristics of the two groups were largely balanced. In multivariate Cox analyses, we found that the location of visceral pleural invasion was not a risk factor for prognosis in the overall population (RFS: P = 0.726, OS: P = 0.599). However, we discovered that relative to patients with peripheral pleura invasion, those with interlobar pleura invasion, PL1 invasion, lesions with greater than 3 cm solid components, and those who underwent segmentectomy had a compromised prognosis. Additionally, tumors larger than 3 cm in size with interlobar pleura invasion showed poor prognosis in patients who underwent postoperative chemotherapy. CONCLUSIONS: In most cases, the location of tumor invasion did not worsen the postoperative prognosis of stage IB non-small cell lung cancer patients with visceral pleural invasion. However, interlobar pleural invasion still had some potential risks compared to that of peripheral pleural invasion.

Serum Exosomes-Based Biomarker circ_0008928 Regulates Cisplatin Sensitivity, Tumor Progression, and Glycolysis Metabolism by miR-488/HK2 Axis in Cisplatin-Resistant Nonsmall Cell Lung Carcinoma.

Background: Nonsmall cell lung carcinoma (NSCLC) is a major cause of cancer-related death worldwide. The resistance of NSCLC to chemical drugs, such as cisplatin (CDDP), poses a heavy burden for NSCLC therapy. Herein, the effects of circular_0008928 (circ_0008928) on the CDDP sensitivity and biological behavior of CDDP-resistant NSCLC cells and underlying mechanism are revealed. Materials and Methods: The expression of circ_0008928 and microRNA-488 (miR-488) was detected by quantitative real-time polymerase chain reaction. The expression of hexokinase 2 (HK2) protein and exosome-specific proteins was determined by Western blot. The half-maximal inhibitory concentration (IC50) value of CDDP was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and migratory and invasive abilities were illustrated by cell counting kit-8 and transwell assays. Cell glycolysis metabolism was illustrated by extracellular acidification rate assay, glucose kit and lactate kit assays and Western blot analysis. The binding sites between miR-488 and circ_0008928 or HK2 were predicted by starbase or microT-CDS online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0008928 expression and HK2 protein expression were significantly upregulated, while miR-488 expression was obviously downregulated in NSCLC cells and CDDP-resistant NSCLC cells. Circ_0008928 expression was increased in serum exosomes of CDDP-resistant NSCLC patients compared with CDDP-sensitive NSCLC patients. In addition, circ_0008928 silencing improved CDDP sensitivity and attenuated CDDP-induced cell proliferation, migration, invasion, and glycolysis metabolism. Circ_0008928 was a sponge of miR-488, and miR-488 bound to HK2 in CDDP-resistant NSCLC cells. Furthermore, both miR-488 inhibitor and HK2 overexpression attenuated circ_0008928 absence-mediated impacts on CDDP sensitivity and tumor process in CDDP-resistant NSCLC. Conclusions: Circ_0008928 knockdown improved CDDP sensitivity and hindered cell proliferation, migration, invasion, and glycolysis metabolism by miR-488/HK2 axis in CDDP-resistant NSCLC. This finding provides a new mechanism for studying CDDP-resistant therapy in NSCLC.

Heteroatom Coordination Regulates Iron Single-Atom-Catalyst with Superior Oxygen Reduction Reaction Performance for Aqueous Zn-Air Battery.

Platinum group metal (PGM)-free M-N-C catalysts have exhibited dramatic electrocatalytic performance and are considered the most promising candidate of the Pt catalysts in oxygen reduction reaction (ORR). However, the electrocatalytic performance of the M-N-C catalysts is still limited by their inferior intrinsic activity and finite active site density. Regulating the coordination environment and increasing the pore structure of the catalyst is an effective strategy to enhance the electrocatalytic performance of the M-N-C catalysts. In this work, the coordination environment and pore structure exquisitely regulated Fe-N-C catalyst exhibit excellent ORR activity and durability. With the enhanced intrinsic activity and increased active site density, the optimized Fe-N/S-C catalyst shows impressive ORR activity (E1/2  = 0.904 V vs reversible hydrogen electrode (RHE)) and superior long-term durability in an alkaline medium. As the advanced physical characterization and theoretical chemistry methods illustrate, the S-modified Fe-Nx (Fe-N3 /S-C) moiety is confirmed as the improved active center for ORR, and the increased active site density further improved ORR efficiency. Based on the Fe-N/S-C cathode, a Zn-air battery is fabricated and shows superior power density (315.4 mW cm-2 ) and long-term discharge stability at 20 mA cm-2 . This work would open a new perspective to design atomically dispersed iron-metal site catalysts for advanced electro-catalysis.

Low expression of INMT is associated with poor prognosis but favorable immunotherapy response in lung adenocarcinoma.

Background: The expression of INMT (indolethylamine N-methyltransferase) has been reported to be downregulated in non-small-cell lung cancer (NSCLC). However, the role of INMT in NSCLC remains elusive. We aim to investigate the underlying mechanisms and clinical value of INMT in NSCLC, especially in lung adenocarcinoma (LUAD). Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of INMT on NSCLC. Gene expression data from an immunotherapy cohort were used to investigate the association of INMT with immunotherapy in NSCLC. Results: INMT expression was significantly downregulated in NSCLC compared with adjacent normal tissues. Downregulated INMT was associated with poor overall survival in LUAD, but not in lung squamous carcinoma. Multivariate Cox regression analysis suggested that INMT was an independent prognostic marker in LUAD. INMT had a reference value in the diagnosis and prognostic estimation of LUAD. Gene set enrichment analysis showed that pathways of the cell cycle and DNA damage response were enriched in the INMT low-expression group. The top 10 hub genes upregulated in the INMT low-expression group mainly activated the cell cycle pathway. In addition, more frequently mutated TP53 genes, higher aneuploidy scores, a fraction of genomes altered, MANTIS scores, and tumor mutation burden were found in tumors with low expression of INMT. Furthermore, patients with low expression of INMT showed favorable clinical benefits to anti-PD-1 treatment with higher enrichment scores of immune-related signatures. Conclusion: The low expression of INMT was associated with poor prognosis but favorable immunotherapy response in LUAD. INMT may affect the progression of LUAD by regulating the cell cycle and may serve as a valuable independent prognostic biomarker in patients with LUAD.

shRNA­mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8.

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.

PARP-1 modulates the expression of miR-223 through histone acetylation to involve in the hydroquinone-induced carcinogenesis of TK6 cells.

The upstream regulators of microRNAs were rarely reported. Hydroquinone (HQ) is the main metabolite of benzene, one of the important environmental factors contributing to leukemia and lymphoma. In HQ-induced malignant transformed TK6 (TK6-HT) cells, the expression of PARP-1 and miR-223 were upregulated. When in PARP-1 silencing TK6-HT cells, miR-223 was downregulated and the apoptotic cell number correspondingly increased. In TK6 cells treated with HQ for different terms, the expression of miR-223 and PARP-1 were dynamically observed and found to be decreased and increased, respectively. Trichostatin A could increase the expression of miR-223, then the expression of HDAC1-2 and nuclear factor kappa B were found to be increased, but that of mH2A was decreased. PARP-1 silencing inhibited the protein expression of H3Ac, mH2A, and H3K27ac. By co-immunoprecipitation experiment, PARP-1 and HDAC2 were found to form a regulatory complex. In conclusion, we demonstrated that the upregulation of PARP-1 mediated activation of acetylation to promote the transcription of miR-223 possibly via coregulating with HDAC2, an epigenetic regulation mechanism involved in cell malignant transformation resulting from long-term exposure to HQ, in which course, H3K27ac might be a specific marker for the activation of histone H3, which also gives hints for benzene exposure research.

Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients.

BACKGROUND: Neoadjuvant immunotherapy is emerging as novel effective intervention in lung cancer, but study to unearth effective surrogates indicating its therapeutic outcomes is limited. We investigated the genetic changes between non-small cell lung cancer (NSCLC) patients with varied response to neoadjuvant immunotherapy and discovered highly potential biomarkers with indicative capability in predicting outcomes. METHODS: In this study, 3 adenocarcinoma and 11 squamous cell carcinoma NSCLC patients were treated by neoadjuvant immunotherapy with variated regimens followed by surgical resection. Treatment-naive FFPE or fresh tissues and blood samples were subjected to whole-exome sequencing (WES). Genetic alternations were compared between differently-responded patients. Findings were further validated in multiple public cohorts. RESULTS: DNA damage repair (DDR)-related InDel signatures and DDR-related gene mutations were enriched in better-responded patients, i.e., major pathological response (MPR) group. Besides, MPR patients exhibited provoked genome instability and unique homologous recombination deficiency (HRD) events. By further inspecting alternation status of homology-dependent recombination (HR) pathway genes, the clonal alternations were exclusively enriched in MPR group. Additionally, associations between HR gene alternations, percentage of viable tumor cells and HRD event were identified, which orchestrated tumor mutational burden (TMB), mutational intratumor heterogeneity (ITH), somatic copy number alteration (SCNA) ITH and clonal neoantigen load in patients. Validations in public cohorts further supported the generality of our findings. CONCLUSIONS: We reported for the first time the association between HRD event and enhanced neoadjuvant immunotherapy response in lung cancer. The power of HRD event in patient therapeutic stratification persisted in multifaceted public cohorts. We propose that HR pathway gene status could serve as novel and additional indicators guiding immune-neoadjuvant and immunotherapy treatment decisions for NSCLC patients.

The outcomes of margin status after sleeve lobectomy for patients of non-small cell lung cancer.

BACKGROUND: Sleeve lobectomy is recognized as an alternative surgical operation to pneumonectomy because it preserves the most pulmonary function and has a considerable prognosis. In this study, we aimed to investigate the implications of residual status for patients after sleeve lobectomy. METHODS: In this retrospective cohort study, we summarized 58 242 patients who underwent surgeries from 2015 to 2018 in Shanghai Chest Hospital and found 456 eligible patients meeting the criteria. The status of R2 was excluded. The outcomes were overall survival (OS) and recurrence-free survival (RFS). We performed a subgroup analysis to further our investigation. RESULTS: After the propensity score match, the baseline characteristic was balanced between two groups. The survival analysis showed no significant difference of overall survival and recurrence-free survival between R0 and R1 groups (OS: p = 0.053; RFS: p = 0.14). In the multivariate Cox analysis, we found that the margin status was not a dependent risk factor to RFS (p = 0.119) and OS (p = 0.093). In the patients of R1, N stage and age were closely related to OS, but we did not find any significant risk variable in RFS for R1 status. In the subgroup analysis, R1 status may have a worse prognosis on patients with more lymph nodes examination. On further investigation, we demonstrated no differences among the four histological types of margin status. CONCLUSION: In our study, we confirmed that the margin status after sleeve lobectomies was not the risk factor to prognosis. However, patients with more lymph nodes resection should pay attention to the margin status.

LINC00173 Interacts With DNMT1 to Regulate LINC00173 Expression via Promoter Methylation in Hydroquinone-Induced Malignantly Transformed TK6 Cells and Benzene-Exposed Workers.

Long-term exposure to benzene or its metabolite, hydroquinone (HQ), can causally contribute to acute myeloid leukemia. Long-noncoding RNAs are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed LINC00173 (long intergenic nonprotein coding RNA 173) regulates the pathogenesis of acute myeloid leukemia is not fully understood. Here, we found that the expression of LINC00173 decreased while the expression of DNA methyltransferase 1 (DNMT1) increased, and the methylation of LINC00173 promoter was negatively correlated with LINC00173 expression in GEPIA, CCLE databases, benzene-exposed workers, B-cell non-Hodgkin's lymphoma, K562, U937, or HQ-induced malignantly transformed TK6 (HQ-MT cells). Furthermore, in 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor) or trichostatin A (histone deacetylation inhibitor)-treated HQ-MT cells, the expression of LINC00173 was restored by reduced DNA promoter methylation levels. HQ-MT cells with DNMT1 knockout by CRISPR/Cas9 restored the expression of LINC00173 and inhibited the DNA methylation of its promoter as well as enrichment of DNMT1 to promoter. Overexpression of LINC00173 inhibited the expression of DNMT1, cell proliferation, tumor growth, enhanced chemosensitivity to cisplatin, and apoptosis in HQ-MT cells. LINC00173 interacts with DNMT1 to regulate the methylation of LINC00173 promoter. Overall, this study provides evidence that interaction between DNMT1 and LINC00173 regulates the expression of LINC00173 by regulating its promoter methylation level, thus regulating the function of HQ-MT cells in vitro and in vivo, providing a new therapeutic target for benzene-induced tumor.

Identification of a 7-miRNA signature for predicting the prognosis of patients with lung adenocarcinoma.

The role of microRNAs (miRNAs) in tumor diagnosis and patients' prognosis has recently gained extensive research attention. This study was designed to analyze miRNA in lung adenocarcinoma (LUAD) using bioinformatics analysis and to identify novel biomarkers to predict overall survival (OS) for LUAD patients. Differential miRNA expression analysis was performed on LUAD, and normal tissues were extracted from The Cancer Genome Atlas (TCGA). Univariate Cox risk regression and least absolute shrinkage and selection operator (LASSO) Cox analysis were used to screen prognostic miRNAs and develop a risk score model. The prognostic performance of the system was examined utilizing the Kaplan-Meier and receiver operating characteristic (ROC) curves. Independent prognostic factors of LUAD were determined by multivariate Cox regression analysis. Nomogram was constructed according to the independent prognostic factors to evaluate the patients' one-, three- and five-year OS. A 7-miRNA signature based on miR-584-5p, miR-31-3p, miR-490-3, miR-4661-5p, miR-30e-5p, miR-582-5p, and miR-148a-3p was established. To categorize patients into high- and low-risk groups, the risk score was computed. The OS of the low-risk group was significantly longer than the high-risk group, and the signature showed high sensitivity and specificity in anticipating the one-, three- and five-year OS. The system was an independent factor in predicting the OS of LUAD patients and performed better when combined with the N stage in nomogram. A 7-miRNA signature developed in this study could accurately predict LUAD survival.

Convergent alteration of lung tissue microbiota and tumor cells in lung cancer.

Microbiota-host interaction plays an important role in cancer predisposing, initiation, progression, and response to therapy. Here, we explored the composition of lung tissue microbiota in 143 Chinese patients through conducting 16S rRNA gene sequencing, while TP53 mutation in tumor cells was assessed simultaneously. We found PAH-degrading microbes were more abundant in lung tumor microbiota from smokers. Furthermore, TP53 mutation was more prevalent in smokers, and TP53-mutated tumor harbored more Massilia, as well as Acidovorax that was also capable of degrading PAH. Further analysis showed DNA recombination and repair pathway was enriched in microbiota of smokers, which was convergent to the alteration occurred in tumor cells. Meanwhile, the microbiota of TP53-mutated tumor also exhibited dysregulation of p53 signaling pathway. Our results provided insights into the association of lung commensal microbes with tobacco exposure and host gene mutation, suggesting microbiota and tumor cells might undergo convergent alteration and mutually benefit each other.