Maintenance treatment of immunotherapy after microwave ablation plus drug-eluting bead bronchial arterial chemoembolization for advanced non-small cell lung cancer: a retrospective single-center cohort study.

Background: The combination therapy of immunotherapy and drug-eluting bead bronchial artery chemoembolization (DEB-BACE) or microwave ablation (MWA) has been attempted as an effective and safe approach for advanced non-small cell lung cancer (NSCLC). However, the outcomes of immunotherapy plus multiple interventional techniques for advanced NSCLC remain unclear. This retrospective study thus aimed to investigate the effectiveness and safety of the maintenance treatment of programmed cell death protein 1 (PD-1) blockade after MWA plus DEB-BACE for advanced NSCLC. Methods: This retrospective cohort study consists of 95 patients with advanced NSCLC who were treated with DEB-BACE between April 2017 and October 2022 and who were allocated to three groups: group A (MWA + DEB-BACE + PD-1 blockade; n=15), group B (MWA + DEB-BACE; n=25), and group C (DEB-BACE alone; n=55). The adverse events (AEs) were compared between the three groups. The outcomes were compared via Kaplan-Meier methods, including median progression-free survival (PFS) and overall survival (OS). Survival analyses were performed via the univariate and multivariate analyses to investigate the prognostic predictors. Results: The overall incidence of AEs in the groups A-C was 53.3% (8/15), 36.0% (9/25), and 32.7% (18/55), respectively, which did not represent a significant difference (P=0.42). No severe AEs (SAEs) occurred. Group A, compared with group B and group C, had a significantly longer estimated median PFS (33.0 vs. 7.0 vs. 3.0 months; P<0.001) and OS (33.0 vs. 13.0 vs. 6.0 months; P=0.002). PD-1 blockade (P=0.006), tumor number (P=0.01), and DEB-BACE/bronchial artery infusion (BAI) chemotherapy cycles (P=0.04) were identified as the predictors of PFS, while the predictors of OS were PD-1 blockade (P<0.001), number of metastases (P<0.001), tumor diameter (P<0.001), and DEB-BACE/BAI cycles (P=0.02). Conclusions: Compared with that of advanced NSCLC treated with MWA plus DEB-BACE or DEB-BACE alone, the maintenance treatment of immunotherapy after MWA plus DEB-BACE might provide a superior prognosis without increasing the risk of AEs.

Comparing the oncologic outcomes of local tumor destruction vs. local tumor excision vs. partial nephrectomy in T1a solid renal masses: a population-based cohort study from the SEER database.

BACKGROUND: There are few large-scale analyses comparing local tumor destruction (LTD) or local tumor enucleation/excision (LTE) relative to partial nephrectomy (PN) for patients with T1a renal masses in terms of cancer-specific survival (CSS) and overall survival (OS). We aimed to compare CSS and OS after LTD versus LTE versus PN. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019), we identified patients with clinical T1a renal masses and histologically confirmed kidney cancer treated with LTD, LTE or PN. After 1:1 ratio propensity score matching (PSM), comparisons between the groups were conducted. Kaplan-Meier analysis and log-rank tests were used to compare survival in the matched population. RESULTS: In the overall cohort of 3717 LTD patients versus 1993 LTE patients versus 26935 PN patients, 77.3% of LTD-treated patients and 74.4% of LTE-treated patients were over 60 years old, while only 50.3% of PN-treated patients were over 60 years old. PN was more strongly associated with CSS (hazard ratio (HR)=1.276, P<0.001) and OS (HR=1.112, P<0.001)) than was LTD, while PN was less strongly associated with CSS (HR=1.040, P=0.230) and OS (HR=0.888, P=0.002) than was LTE, not only in the PSM cohort but also in the subgroups of patients with a tumor size ≤3 cm and patients with a tumor size of 3.1-4 cm. CONCLUSIONS: In clinical T1a solid renal mass patients, LTD was associated with lower CSS and OS than LTE and PN, while LTE demonstrated noninferior CSS and superior OS to PN regardless of tumor size.

Electrochemical Continuous-Flow Scholl Reaction toward Polycyclic Aromatic Hydrocarbons.

The preparation of polycyclic aromatic hydrocarbons (PAHs) by the Scholl reaction is typically performed by using superstoichiometric oxidants. Herein, we develop an electrochemical continuous-flow Scholl reaction to access PAHs that features a reduction in the use of supporting electrolytes and easy scale-up without changing the reaction conditions and setups. This reaction allows the synthesis of distorted PAHs containing three [5]helicene units that possess intriguing electronic and optical properties.

Genome-Wide Identification of LOX Gene Family and Its Expression Analysis under Abiotic Stress in Potato (Solanum tuberosum L.).

The lipoxygenases (LOXs) are non-heme iron-containing dioxygenases that play an important role in plant growth and defense responses. There is scarce knowledge regarding the LOX gene family members and their involvement in biotic and abiotic stresses in potato. In this study, a total of 17 gene family members (StLOXs) in potato were identified and clustered into three subfamilies: 9-LOX type I, 13-LOX type I, and 13-LOX type II, with eleven, one, and five members in each subfamily based on phylogenetic analysis. By exploiting the RNA-seq data in the Potato Genome Sequencing Consortium (PGSC) database, the tissue-specific expressed and stress-responsive StLOX genes in double-monoploid (DM) potato were obtained. Furthermore, six candidate StLOX genes that might participate in drought and salt response were determined via qPCR analysis in tetraploid potato cultivars under NaCl and PEG treatment. Finally, the involvement in salt stress response of two StLOX genes, which were significantly up-regulated in both DM and tetraploid potato under NaCl and PEG treatment, was confirmed via heterologous expression in yeast under salt treatment. Our comprehensive analysis of the StLOX family provides a theoretical basis for the potential biological functions of StLOXs in the adaptation mechanisms of potato to stress conditions.

Density Functional Theory Calculations on Fluorescence-Enhanced Mechanisms of the Optical Sensor for Zinc Ions, ADPA.

N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine (ADPA) as a specific ion sensor for Zn2+ has been widely applied. Although the photo-induced electron transfer (PET) mechanism was proposed previously, its fluorescence-enhanced effect still remains somewhat ambiguous, according to unknown influences of non-radiative energy decay pathways, such as intersystem crossing and internal conversion. Herein, a thorough study using density functional theory has been performed for low-lying electronic states of the ADPA monomer and hydrated ADPA-Zn2+ complex. Based on interfragment charge transfer analyses, we quantitatively calculated the amount of transferred electrons in the monomer and complex, providing solid evidences for the PET mechanism and in line with the conclusion of frontier molecular orbital analyses. Moreover, the ISC process of S1→T2 was confirmed to play a considerable role in the excitation energy relaxation process of the ADPA monomer, but this influence was significantly suppressed in the hydrated ADPA-Zn2+ complex. These results provide additional clues for the design of new metal ion-specific fluorescence probes.

Current-Controlled Electrochemical Approach Toward Mono- and Trifluorinated Isoindolin-1-one Derivatives.

An electrochemical intramolecular 5-exo-dig aza-cyclization of 2-alkynylbenzamides and subsequent nucleophilic fluorination have been developed to afford the highly selective synthesis of mono- and trifluorinated isoindolin-1-one derivatives. This work demonstrates the unique capability of synthetic electrochemistry in controlling reaction selectivity through the applied electrolytic parameters. In addition, the obtained monofluorinated 3-methyleneisoindolin-1-one (19) displays interesting photophysical properties that are not observed in its nonfluorinated analog.

Comprehensive Characterization of the C3HC4 RING Finger Gene Family in Potato (Solanum tuberosum L.): Insights into Their Involvement in Anthocyanin Biosynthesis.

The C3HC4 RING finger gene (RING-HC) family is a zinc finger protein crucial to plant growth. However, there have been no studies on the RING-HC gene family in potato. In this study, 77 putative StRING-HCs were identified in the potato genome and grouped into three clusters based on phylogenetic relationships, the chromosome distribution, gene structure, conserved motif, gene duplication events, and synteny relationships, and cis-acting elements were systematically analyzed. By analyzing RNA-seq data of potato cultivars, the candidate StRING-HC genes that might participate in tissue development, abiotic stress, especially drought stress, and anthocyanin biosynthesis were further determined. Finally, a StRING-HC gene (Soltu.DM.09G017280 annotated as StRNF4-like), which was highly expressed in pigmented potato tubers was focused on. StRNF4-like localized in the nucleus, and Y2H assays showed that it could interact with the anthocyanin-regulating transcription factors (TFs) StbHLH1 of potato tubers, which is localized in the nucleus and membrane. Transient assays showed that StRNF4-like repressed anthocyanin accumulation in the leaves of Nicotiana tabacum and Nicotiana benthamiana by directly suppressing the activity of the dihydroflavonol reductase (DFR) promoter activated by StAN1 and StbHLH1. The results suggest that StRNF4-like might repress anthocyanin accumulation in potato tubers by interacting with StbHLH1. Our comprehensive analysis of the potato StRING-HCs family contributes valuable knowledge to the understanding of their functions in potato development, abiotic stress, hormone signaling, and anthocyanin biosynthesis.

Genome-wide analysis of the U-box E3 ligases gene family in potato (Solanum tuberosum L.) and overexpress StPUB25 enhance drought tolerance in transgenic Arabidopsis.

BACKGROUND: Plant U-box (PUB) E3 ubiquitin ligases have vital effects on various biological processes. Therefore, a comprehensive and systematic identification of the members of the U-box gene family in potato will help to understand the evolution and function of U-box E3 ubiquitin ligases in plants. RESULTS: This work identified altogether 74 PUBs in the potato (StPUBs) and examined their gene structures, chromosomal distributions, and conserved motifs. There were seventy-four StPUB genes on ten chromosomes with diverse densities. As revealed by phylogenetic analysis on PUBs within potato, Arabidopsis, tomato (Solanum lycopersicum), cabbage (Brassica oleracea), rice (Oryza sativa), and corn (Zea mays), were clustered into eight subclasses (C1-C8). According to synteny analysis, there were 40 orthologous StPUB genes to Arabidopsis, 58 to tomato, 28 to cabbage, 7 to rice, and 8 to corn. In addition, RNA-seq data downloaded from PGSC were utilized to reveal StPUBs' abiotic stress responses and tissue-specific expression in the doubled-monoploid potato (DM). Inaddition, we performed RNA-seq on the 'Atlantic' (drought-sensitive cultivar, DS) and the 'Qingshu NO.9' (drought-tolerant cultivar, DT) in early flowering, full-blooming, along with flower-falling stages to detect genes that might be involved in response to drought stress. Finally, quantitative real-time PCR (qPCR) was carried out to analyze three candidate genes for their expression levels within 100 mM NaCl- and 10% PEG 6000 (w/v)-treated potato plantlets for a 24-h period. Furthermore, we analyzed the drought tolerance of StPUB25 transgenic plants and found that overexpression of StPUB25 significantly increased peroxidase (POD) activity, reduced ROS (reactive oxygen species) and MDA (malondialdehyde) accumulation compared with wild-type (WT) plants, and enhancing drought tolerance of the transgenic plants. CONCLUSION: In this study, three candidate genes related to drought tolerance in potato were excavated, and the function of StPUB25 under drought stress was verified. These results should provide valuable information to understand the potato StPUB gene family and investigate the molecular mechanisms of StPUBs regulating potato drought tolerance.

Synthesis, Characterization, and Properties of Sila-Annulated Phenanthrene Imides.

A series of sila-annulated phenanthrene imides were synthesized through a three-step synthetic route, which represent a hybrid class of biphenyl-based π-conjugated molecules incorporating an imide unit and silole. A comprehensive investigation of their structural, photophysical, and electronic properties was studied by experiment and theoretical calculations. Notably, sila-annulated phenanthrene imides with significant aggregation-induced emission (AIE) properties were observed.

Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation.

OBJECTIVE: Proinflammatory necroptosis is the main pathological mechanism of ischemic stroke. Homer scaffolding protein 1 (Homer1) is a postsynaptic scaffolding protein that exerts anti-inflammatory effects in most central nervous system diseases. However, the relationship between Homer1 and proinflammatory necroptosis in ischemic stroke remains unclear. AIM: This study aimed to investigate the role of Homer1 in ischemia-induced necroptosis. METHODS: C57BL/6 mice were used to establish a model of permanent middle cerebral artery occlusion model (pMCAO). Homer1 knockdown mice were generated using adeno-associated virus (AAV) infection to explore the role of Homer1 and its impact on necroptosis in pMCAO. Finally, Homer1 protein was stereotaxically injected into the ischemic cortex of Homer1flox/flox/Nestin-Cre +/- mice, and the efficacy of Homer1 was investigated using behavioral assays and molecular biological assays to explore potential mechanisms. RESULTS: Homer1 expression peaked at 8 h in the ischemic penumbral cortex after pMCAO and colocalized with neurons. Homer1 knockdown promoted neuronal death by enhancing necroptotic signaling pathways and aggravating ischemic brain damage in mice. Furthermore, the knockdown of Homer1 enhanced the expression of proinflammatory cytokines. Moreover, injection of Homer1 protein reduced necroptosis-induced brain injury inhibited the expression of proinflammatory factors, and ameliorated the outcomes in the Homer1flox/flox/Nestin-Cre+/- mice after pMCAO. CONCLUSIONS: Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation. These data suggested that Homer1 is a novel regulator of neuronal death and neuroinflammation.

Exploring BODIPY derivatives as sonosensitizers for anticancer sonodynamic therapy.

Sonodynamic therapy (SDT) is an emerging non-invasive and effective therapeutic modality for cancer treatment bearing benefit of deep tissue-penetration in comparison to photo-inspired therapy. However, exploring novel sonosensitizers with high sonosensitivity and desirable biosafety remains a significant challenge. Although boron dipyrromethene (BODIPY) dyes have been widely used in biomedical filed, no BODIPY-based sonosensitizers have been reported yet. Herein, we synthesized four BODIPY dyes (BDP1-BDP4) and investigated their potential applications in SDT. BDP4 exhibited superb sonosensitivity and high SDT efficiency against cancer cells and tumors in tumor-bearing mice. The types of the generated reactive oxygen species, cavitation effect, and cell apoptosis were investigated to figure out the sonodynamic therapeutic mechanisms of BDP4. This work for the first time demonstrates the potential of BODIPY dyes as novel sonosensitizers for SDT, which may pave an avenue for developing more efficient and safer sonosensitizers in future.

Surgical treatment of Behcet's disease with severe aortic regurgitation.

Behcet's disease (BD) is a multisystem inflammatory disease that is characterized by oral aphthosis, genital aphthosis, ocular lesions, and cutaneous lesions. Although BD rarely affects the cardiovascular system, its symptoms can be shown as aortic regurgitation (AR), which requires surgical intervention. Due to the special pathogenesis of BD, a low preoperative diagnosis rate and a high incidence of serious complications, such as perivalvular leakage, valve detachment, and pseudoaneurysm after prosthetic valve replacement, surgical treatment of BD with severe AR has a poor prognosis. In recent years, new surgical strategies have been developed to improve treatment efficacy for this disease. This article reviews and summarizes the evolution of surgical techniques for BD with AR and aims to provide a reference for optimizing surgical strategies, improving perioperative management, and assisting prognosis in patients suffering from BD with severe AR.

Off-pump vs. on-pump bypass surgery grafting in diabetic patients with three-vessel disease: a propensity score matching study.

Background: Controversy exists regarding the advantages and risks of off-pump vs. on-pump coronary artery bypass grafting (CABG) for patients with diabetes. We therefore compare the early clinical outcomes of off-pump vs. on-pump procedures for diabetic patients with three-vessel disease. Materials and methods: We conducted a retrospective analysis of clinical data obtained from 548 diabetic patients with three-vessel coronary artery disease who underwent isolated CABG between January 2016 and June 2020. To adjust the differences of baseline characteristics between the off-pump CABG (OPCAB) and on-pump CABG (ONCAB) groups, propensity score matching (PSM) was used. Following 1:1 matching, we selected 187 pairs of patients for further comparison of outcomes within the first 30 days after surgery. Results: The preoperative characteristics of the patients between the two groups were clinically comparable after PSM. The OPCAB group exhibited a significantly higher incidence of incomplete revascularization (27.3% vs. 14.4%; P = 0.002) compared with the ONCAB group. No differences were seen in mortality within 30 days between the matched groups (1.1% vs. 3.7%; P = 0.174). Notably, the OPCAB group had a lower risk of respiratory failure or infection (2.1% vs. 7.0%; P = 0.025), less postoperative stroke (1.1% vs. 4.8%; P = 0.032), and reduced postoperative ventilator assistance time (35.8 ± 33.7 vs. 50.9 ± 64.8; P = 0.005). Conclusion: OPCAB in diabetic patients with three-vessel disease is a safe procedure with reduced early stroke and respiratory complications and similar mortality rate, myocardial infarction, and renal failure requiring dialysis to conventional on-pump revascularization.

Safety and efficacy of CT-guided percutaneous microwave ablation for stage I non-small cell lung cancer in patients with comorbid idiopathic pulmonary fibrosis.

OBJECTIVES: To evaluate the safety and efficacy of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) in patients with idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: A retrospective single-center cohort study was conducted in patients with clinical stage I NSCLC who underwent CT-guided MWA from Nov 2016 to Oct 2021. The patients were divided into the IPF group and the non-IPF group. The primary endpoints were 90-day adverse events and hospital length of stay (HLOS). The secondary endpoints included overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 107 patients (27 with IPF and 80 without IPF) were finally included for analysis. No procedure-related acute exacerbation of IPF or death occurred post-MWA. The rates of adverse events were similar between the groups (48.6% vs. 47.7%; p = 0.998). The incidence of grade 3 adverse events in the IPF group was higher than that in the non-IPF group without a significant difference (13.5% vs. 4.6%; p = 0.123). Median HLOS was 5 days in both groups without a significant difference (p = 0.078). The 1-year and 3-year OS were 85.2%/51.6% in the IPF group, and 97.5%/86.4% in the non-IPF group. The survival of patients with IPF was significantly poorer than the survival of patients without IPF (p < 0.001). There was no significant difference for PFS (p = 0.271). CONCLUSION: MWA was feasible in the treatment of stage I NSCLC in patients with IPF. IPF had an adverse effect on the survival of stage I NSCLC treated with MWA. CLINICAL RELEVANCE STATEMENT: CT-guided microwave ablation is a well-tolerated and effective potential alternative treatment for stage I non-small cell lung cancer in patients with idiopathic pulmonary fibrosis. KEY POINTS: • Microwave ablation for stage I non-small cell lung cancer was well-tolerated without procedure-related acute exacerbation of idiopathic pulmonary fibrosis and death in patients with idiopathic pulmonary fibrosis. • No differences were observed in the incidence of adverse events between patients with idiopathic pulmonary fibrosis and those without idiopathic pulmonary fibrosis after microwave ablation (48.6% vs. 47.7%; p = 0.998). • The 1-year and 3-year overall survival rates (85.2%/51.6%) in the idiopathic pulmonary fibrosis group were worse than those in the non- idiopathic pulmonary fibrosis group (97.5%/86.4%) (p < 0.001).

TSG-SLAM: SLAM Employing Tight Coupling of Instance Segmentation and Geometric Constraints in Complex Dynamic Environments.

Although numerous effective Simultaneous Localization and Mapping (SLAM) systems have been developed, complex dynamic environments continue to present challenges, such as managing moving objects and enabling robots to comprehend environments. This paper focuses on a visual SLAM method specifically designed for complex dynamic environments. Our approach proposes a dynamic feature removal module based on the tight coupling of instance segmentation and multi-view geometric constraints (TSG). This method seamlessly integrates semantic information with geometric constraint data, using the fundamental matrix as a connecting element. In particular, instance segmentation is performed on frames to eliminate all dynamic and potentially dynamic features, retaining only reliable static features for sequential feature matching and acquiring a dependable fundamental matrix. Subsequently, based on this matrix, true dynamic features are identified and removed by capitalizing on multi-view geometry constraints while preserving reliable static features for further tracking and mapping. An instance-level semantic map of the global scenario is constructed to enhance the perception and understanding of complex dynamic environments. The proposed method is assessed on TUM datasets and in real-world scenarios, demonstrating that TSG-SLAM exhibits superior performance in detecting and eliminating dynamic feature points and obtains good localization accuracy in dynamic environments.

Synchronous percutaneous core-needle biopsy and microwave ablation for stage I non-small cell lung cancer in patients with Idiopathic pulmonary fibrosis: initial experience.

PURPOSE: This study aimed to retrospectively evaluate the safety and feasibility of computed tomography (CT)-guided synchronous percutaneous core-needle biopsy (CNB) and microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) in patients with idiopathic pulmonary fibrosis (IPF). METHODS: From January 2019 to January 2023, nineteen stage I NSCLC patients with IPF underwent CT-guided synchronous percutaneous CNB and MWA in this study. The technical success rate, complications, local tumor progression (LTP) and overall survival (OS) were observed, and the effect of synchronous percutaneous CNB and MWA were evaluated. RESULTS: The technical success rate of synchronous percutaneous CNB and MWA was 100%. With a median follow-up time of 20.36 months, the median OS was 25 months (95% CI: 21.79, 28.20). The six-, twelve- and eighteen-month OS rates were 94.73%, 89.47% and 57.89%, respectively. The six-, twelve- and eighteen-month LTP rates were 0%, 10.52% and 31.57%, respectively. Major complications including pneumothorax, bronchopleural fistula and pneumonia occurred in 26.32% (5/19) patients. None of the patients died during the procedure. CONCLUSIONS: According to the results of the current study, CT-guided synchronous percutaneous CNB and MWA appears to be a safe and effective for stage I NSCLC in patients with IPF and providing an alternative therapeutic option for local control of pulmonary malignancy in high-risk patients.

Percutaneous core-needle biopsy before and immediately after coaxial microwave ablation in solid non-small cell lung cancer: the comparison of genomic testing from specimens.

PURPOSE: To compare the genomic testing based on specimens obtained from percutaneous core-needle biopsy (CNB) before and immediately after coaxial microwave ablation (MWA) in solid non-small cell lung cancer (NSCLC), and to investigate the diagnostic performance of CNB immediately after coaxial MWA in solid NSCLC. METHODS: Coaxial MWA and CNB were performed for NSCLC patients, with a power of 30 or 40 watts (W) in MWA between the pre- and post-ablation CNB, followed by continuous ablation after the second CNB on demand. The paired specimens derived from the same patient were compared for pathological diagnosis and genomic testing. DNA/RNA extracted from the paired specimens were also compared. RESULTS: A total of 33 NSCLC patients with solid lesions were included. There were two patients (6.1%) without atypical cells and three patients (9.1%) who had the technical failure of genomic testing in post-ablation CNB. The concordance rate of pathological diagnosis between the twice CNB was 93.9% (kappa = 0.852), while that of genomic testing was 90.9% (kappa = 0.891). For the comparisons of DNA/RNA extracted from pre- and post-ablation CNB in 30 patients, no significant difference was found when the MWA between twice CNB has a power of 30 or 40 W and ablation time within five minutes (P = 0.174). CONCLUSIONS: If the pre-ablation CNB presented with a high risk of pneumothorax or hemorrhage, the post-ablation CNB could be performed to achieve accurate pathological diagnosis and genomic testing and the maximum effect of ablation, which might allow for the diagnosis of genomic testing in 90.9% of solid NSCLC.

Drug-eluting beads bronchial arterial chemoembolization/bronchial arterial infusion chemotherapy with and without PD-1 blockade for advanced non-small cell lung cancer: a comparative single-center cohort study.

Background: Drug-eluting beads bronchial arterial chemoembolization (DEB-BACE)/bronchial artery infusion chemotherapy (BAI) have been investigated as treatment options for advanced non-small cell lung cancer (NSCLC), especially for those patients who develop refractoriness to or are intolerant to systemic chemotherapy. This retrospective study aimed to compare the outcomes of DEB-BACE/BAI with and without programmed cell death protein 1 (PD-1) blockade for advanced NSCLC, and to investigate the effectiveness and safety of combination regimens. Methods: This retrospective cohort study included advanced NSCLC patients who were intolerant to or were resistant to systemic chemotherapy, radiotherapy, or molecular targeted therapy and underwent DEB-BACE/BAI between October 2016 and October 2021 in Beijing Hospital, National Center of Gerontology. A total of 84 advanced NSCLC patients (DEB-BACE/BAI + PD-1 blockade group: group A, n=27; DEB-BACE/BAI: group B, n=57) were enrolled finally. The embolic agent CalliSpheres (100-300, 300-500, or 500-700 µm) loaded with gemcitabine (800 mg) was administered during the DEB-BACE procedure. The adverse events (AEs) and outcomes were compared. Of these, the median progression-free survival (PFS) and overall survival (OS) were compared via Kaplan-Meier (KM) methods. Univariate and multivariate Cox regression analyses were used to investigate the predictors of PFS and OS. Results: KM methods showed that group A had longer median PFS (12.0 vs. 3.0 months, P<0.001) and OS (27.0 vs. 8.0 months, P<0.001) than group B. The predictors of PFS for DEB-BACE/BAI included tumor diameter (P=0.013), immunotherapy (P<0.001), and DEB-BACE/BAI cycles (P=0.012), whereas the predictors of OS included tumor diameter (P=0.021), extrapulmonary metastases (P=0.041), immunotherapy (P<0.001), and DEB-BACE/BAI cycles (P=0.020). The incidence rates of overall AEs in groups A and B were 40.7% (11/27) and 36.8% (21/57), respectively, and no significant difference was found (P=0.731). Group A had an incidence rate of 11.1% for grade 3 immunotherapy-related AEs (irAEs). There were no incidences of ectopic embolization or spinal artery injury. Conclusions: Compared with DEB-BACE/BAI, PD-1 blockade plus DEB-BACE/BAI could improve the prognosis for advanced NSCLC despite the associated risk of grade 3 irAEs. The combination regimens are promising and safe approaches for advanced NSCLC.

Mechanism of lncRNA FOXD3-AS1/miR-338-3p in the malignant progression of nasopharyngeal carcinoma through ceRNA.

This work aimed to analyze the impact of lncRNA FOXD3-AS1 (F-A) on the regulation of miR-338-3p (M) on the proliferation (Pro), migration (Mig), and invasion (Inv) of nasopharyngeal carcinoma (NPC) cells. F-A and M levels in human normal nasopharyngeal (NNP) NP69 cells and NPC CNE1 and CNE2 cells were detected by real-time quantitative PCR. After transfection or cotransfection with F-A shRNA, miR-338-3p mimic (MM), and miR-338-3p inhibitor (MI), cell Pro, Mig, and Inv (PMI) were detected using CCK-8, scratch healing, and Transwell chamber experiments, respectively. As a result, relative to NP69 cells, F-A was upregulated in CNE1 and CNE2 cells, while M was downregulated (P<0.01). F-A in CNE1 and CNE2 cells was downregulated and M was upregulated relative to shF-A (P<0.01). Furthermore, shF-A and MM groups demonstrated drastically reduced cell proliferative activity, Mig, and Inv versus CNE1/CNE2 groups. The cell proliferative activity, Mig, and Inv number of the MI group increased substantially (P<0.01). The shF-A+MM group exhibited markedly reduced cell proliferative activity, Mig, and cell number of Inv relative to those of CNE1/CNE2 (P<0.01). Moreover, the shF-A+MI group exhibited greatly increased cell proliferative activity, Mig, and cell number of Inv versus the shF-A+MM group (P<0.01). In short, lncRNA F-A level was abnormally upregulated, and that of M was downregulated in NPC. Interfering with lncRNA F-A level can upregulate M expression. Silencing of lncRNA F-A can inhibit PMI of NPC cells.

Extracellular Matrix Stiffness Regulates Microvascular Stability by Controlling Endothelial Paracrine Signaling to Determine Pericyte Fate.

BACKGROUND: The differentiation of pericytes into myofibroblasts causes microvascular degeneration, ECM (extracellular matrix) accumulation, and tissue stiffening, characteristics of fibrotic diseases. It is unclear how pericyte-myofibroblast differentiation is regulated in the microvascular environment. Our previous study established a novel 2-dimensional platform for coculturing microvascular endothelial cells (ECs) and pericytes derived from the same tissue. This study investigated how ECM stiffness regulated microvascular ECs, pericytes, and their interactions. METHODS: Primary microvessels were cultured in the TGM2D medium (tubular microvascular growth medium on 2-dimensional substrates). Stiff ECM was prepared by incubating ECM solution in regular culture dishes for 1 hour followed by PBS wash. Soft ECM with Young modulus of ≈6 kPa was used unless otherwise noted. Bone grafts were prepared from the rat skull. Immunostaining, RNA sequencing, RT-qPCR (real-time quantitative polymerase chain reaction), Western blotting, and knockdown experiments were performed on the cells. RESULTS: Primary microvascular pericytes differentiated into myofibroblasts (NG2+αSMA+) on stiff ECM, even with the TGFß (transforming growth factor beta) signaling inhibitor A83-01. Soft ECM and A83-01 cooperatively maintained microvascular stability while inhibiting pericyte-myofibroblast differentiation (NG2+αSMA-/low). We thus defined 2 pericyte subpopulations: primary (NG2+αSMA-/low) and activated (NG2+αSMA+) pericytes. Soft ECM promoted microvascular regeneration and inhibited fibrosis in bone graft transplantation in vivo. As integrins are the major mechanosensor, we performed RT-qPCR screening of integrin family members and found Itgb1 (integrin ß1) was the major subunit downregulated by soft ECM and A83-01 treatment. Knocking down Itgb1 suppressed myofibroblast differentiation on stiff ECM. Interestingly, ITGB1 phosphorylation (Y783) was mainly located on microvascular ECs on stiff ECM, which promoted EC secretion of paracrine factors, including CTGF (connective tissue growth factor), to induce pericyte-myofibroblast differentiation. CTGF knockdown or monoclonal antibody treatment partially reduced myofibroblast differentiation, implying the participation of multiple pathways in fibrosis formation. CONCLUSIONS: ECM stiffness and TGFß signaling cooperatively regulate microvascular stability and pericyte-myofibroblast differentiation. Stiff ECM promotes EC ITGB1 phosphorylation (Y783) and CTGF secretion, which induces pericyte-myofibroblast differentiation.