Chiral inversion induced by aromatic interactions in short peptide assembly.

Although hydrophobic interactions provide the main driving force for initial peptide aggregation, their role in regulating suprastructure handedness of higher-order architectures remains largely unknown. We here interrogate the effects of hydrophobic amino acids on handedness at various assembly stages of peptide amphiphiles. Our studies reveal that relative to aliphatic side chains, aromatic side chains set the twisting directions of single ß-strands due to their strong steric repulsion to the backbone, and upon packing into multi-stranded ß-sheets, the side-chain aromatic interactions between strands form the aromatic ladders with a directional preference. This ordering not only leads to parallel ß-sheet arrangements but also induces the chiral flipping over of single ß-strands within a ß-sheet. In contrast, the lack of orientational hydrophobic interactions in the assembly of aliphatic peptides implies no chiral inversion upon packing into ß-sheets. This study opens an avenue to harness peptide aggregates with targeted handedness via aromatic side-chain interactions.

Anatomical characteristics of superior and subsuperior segment in right lower lobe based on three-dimensional reconstruction.

OBJECTIVE: Segmentectomy has been widely performed in clinical practice, which required a comprehensive understanding of anatomical structure. In right lower lobe, studies of superior segment (S6) were relatively small-sized. And only one study focusing on subsuperior segment (S∗) was published, which showed different results with previous ones. As the close relationship between S6 and S∗, variation types and their prevalence rate were reported, aiming to providing larger-size study of S6 and showing new evidence on anatomical structure of S∗. METHODS: 800 CT imaging data were collected from patients in our hospital. Three-dimensional reconstruction was performed after quality check. All images were screened according to the definition of corresponding segment and anatomical variations were analyzed. RESULTS: The proportion of S6 variation types in the largest scale (718 patients) was reported with no significant difference compared to previous studies and newly classified subtypes of two-stem V6. The prevalence rate for S∗ in right lower lobe reached 28.3 % (203/718) with similar proportion of three types. Variation types and origins of pulmonary artery were analyzed in detail, finding two-stem A∗ only be observed in type III B∗. CONCLUSIONS: Through this study, the variation types and incidence rate of S6 were confirmed, and a different result of S∗ has been provided as well. The feasibility of the current classification standards and proposed new subclassifications were verified. The results would be a supplement to lung segmental anatomy and could advance researches in the future.

Amino acid-induced synthesis of chiral AgAuPt nanoparticles with branched structure for circularly polarized enantioselective photoelectrocatalytic water splitting.

Chiral Plasmonic nanomaterials have gradually illustrated intriguing circularly polarized light (CPL)-dependent properties in photocatalysis due to their unique chiral optical activity. However, the connection between chiral characteristics and catalytic performance of these materials in cooperative systems is rarely reported and remains a challenge task. In this work, branched AgAuPt nanoparticles induced by L/d-cysteine (Cys) with strong and perfectly symmetric circular dichroism (CD) signals are synthesized. Chiral branched AgAuPt nanoparticles firstly exhibit superior typical electrocatalytic performance. In the photoelectrocatalytic system, chiral branched AgAuPt nanoparticles demonstrate selective catalytic water splitting performance. Specifically, chiral branched AgAuPt with related CPL irradiation exhibits enhanced acidic hydrogen evolution reaction (HER) performance. Under the continuous irradiation of related CPL, the chiral catalyst generates more heat, which further increases the catalytic activity. This contribution of heat is supported by density functional theory (DFT) calculation results. The changes in chiroptical activity during this process are recorded by variable temperature CD spectra. This work provides a novel paradigm for designing chiral catalysis systems and emphasizes the profound promise of chiral plasmonic nanomaterials as chiral catalysts.

A successful endovascular aortic repair of aortoesophageal fistula following esophagectomy: a case report and literature review.

BACKGROUND: Aortoesophageal fistula (AEF) is an extremely rare and highly fatal complication leading to a high risk of morbidity and mortality. Successful management of AEF after esophagectomy for esophageal carcinoma has rarely been reported in the literature. CASE PRESENTATION: Here we present a rare case of a 44-year-old female with complications of AEF after esophagectomy for esophageal carcinoma, mainly presented as vomiting of blood. Both computed tomographic and computed tomography angiography of the chest showed bilateral pleural effusion and atelectasis, while gastroscopy showed large gastrointestinal bleeding. Emergency surgery was performed that included the removal of the mediastinal abscess, left lower pulmonary wedge resection, and thoracic endovascular aortic repair (TEVAR), followed by supportive treatment. The surgery went successful, and the patient was followed up for 1 year after discharge and showed good recovery. We also reviewed previous literature on the history, causes, pathophysiology, clinical presentation, diagnosis, and treatment of AEF after esophagectomy for esophageal adenocarcinoma. CONCLUSIONS: In our case, thoracotomy combined with TEVAR was effective in treating AEF after esophagectomy for esophageal adenocarcinoma. This case provides successful experiences for clinical diagnosis and treatment of AEF after esophagectomy for esophageal carcinoma.

What happens when left meets right under equimolar and non-equimolar co-assembly of short peptide stereoisomers?

The co-assembly of different peptide chains usually leads to the formation of intricate architectures and sophisticated functions in biological systems. Although the co-assembly of stereoisomeric peptides represents a facile and flexible strategy for the synthesis of peptide-based nanomaterials with novel structures and potentially interesting properties, there is a lack of a general knowledge on how different isomers pack during assembly. Through the combined use of simulations and experimental observations, we report that heterochiral pairing is preferred to homochiral pairing at the molecular scale but self-sorting dictates beyond the molecular level for the mixtures of the short stereoisomeric ß-sheet peptides I3K (Ile-Ile-Ile-Lys). Furthermore, we demonstrate that flat ß-sheets and fibril morphology are always preferred to twisted ones during heterochiral pairing and subsequent assembly. However, the heterochiral pairing into flat morphology is not always at an equimolar ratio. Instead, a non-equimolar ratio (1:2) is observed for the mixing of homochiral LI3LK and heterochiral LI3DK, whose strand twisting degrees differ greatly. Such a study provides a paradigm for understanding the co-assembly of stereoisomeric peptides at the molecular scale and harnessing their blending for targeted nanostructures.

Amino acid-mediated amorphous copper sulphide with enhanced photothermal conversion efficiency for antibacterial application.

Pathogenic bacteria in daily life, such as Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), often seriously affect human life and health. The extensive use of antibiotics has led to the emergence of drug-resistant bacteria, so it is urgent to develop efficient and non-drug-resistant sterilization methods. Here, we use small-molecule cysteine (Cys) as an auxiliary agent to synthesize spherical porous amorphous CuS-Cysteine (CuS-C) nanoparticles, which have good dispersion in aqueous solutions, and explore the reaction mechanism of Cys-induced CuS synthesis. The synthesized composite nanomaterials have strong near-infrared light absorption ability and efficient photothermal conversion ability and can effectively ablate pathogenic bacteria under the irradiation of an 808 nm laser. In addition, antibacterial experiments showed that CuS-C composites had no bactericidal effect without near-infrared light, but they had a good photothermal bactericidal effect on S. aureus and E. coli under radiation conditions. Considering the simple synthesis process, strong photothermal conversion ability, low cost, and suitability for large-scale production, CuS-C nanocomposites, as a promising antibacterial material, will provide a feasible scheme for the treatment of drug-resistant pathogens.

The predictive role of hematologic markers in resectable NSCLC patients treated with neoadjuvant chemoimmunotherapy: a retrospective cohort study.

BACKGROUND: Neoadjuvant chemoimmunotherapy is an important therapeutic modality for resectable nonsmall cell lung cancer (NSCLC). The roles of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in predicting the efficacy and prognosis of patients with resectable NSCLC receiving neoadjuvant chemoimmunotherapy remain uncertain. This study aimed to explore the association of baseline and preoperative NLR, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio with the treatment response and survival of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy. MATERIALS AND METHODS: Data of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy between May 2019 and July 2022 at our institute, were retrospectively analyzed. Peripheral blood cell counts were obtained at baseline and before surgery. Data that may affect treatment efficacy were also collected and analyzed, including age, sex, BMI, cumulative smoking exposure, pathological type, clinical stage, PD-L1 tumor proportion score, immune checkpoint inhibitors, dosage of neoadjuvant therapy, duration from final therapy to surgery, and baseline and preoperative oncological markers. The present work has been reported in compliance with REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria and guidelines (Supplemental Digital Content 1, http://links.lww.com/JS9/A860 ). RESULTS: A total of 116 patients were included in the study. Univariate logistic regression analysis showed that a higher baseline NLR ( P =0.001) and preoperative NLR ( P =0.001) were associated with a lower incidence of pathological complete response (pCR) following neoadjuvant therapy. Multivariate analysis indicated that a lower incidence of pCR was achieved in the high baseline NLR group ( P =0.014). Higher baseline NLR ( P =0.021), preoperative NLR ( P =0.004) and higher preoperative CEA levels ( P =0.059) were associated with shorter disease-free survival (DFS). Multivariate Cox proportional hazard regression analyses showed that shorter DFS was achieved in the high preoperative NLR group ( P =0.033). CONCLUSION: In patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy, a higher baseline NLR was associated with a lower incidence of pCR, and a higher preoperative NLR was associated with a shorter DFS. However, a future prospective study with a large sample size and long-term follow-up is needed to verify the predictive value of NLR in these patients.

Effect of Achiral Glycine Residue on the Handedness of Surfactant-Like Short Peptide Self-Assembly Nanofibers.

Surfactant-like short peptides are a kind of ideal model for the study of chiral self-assembly. At present, there are few studies on the chiral self-assembly of multicharged surfactant-like peptides. In this study, we adopted a series of short peptides of Ac-I4KGK-NH2 with different combinations of L-lysine and D-lysine residues as the model molecules. TEM, AFM and SANS results showed that Ac-I4LKGLK-NH2, Ac-I4LKGDK-NH2, and Ac-I4DKGLK-NH2 formed the morphologies of nanofibers, and Ac-I4DKGDK-NH2 formed nanoribbons. All the self-assembled nanofibers, including the intermediate nanofibers of Ac-I4DKGDK-NH2 nanoribbons, showed the chirality of left handedness. Based on the molecular simulation results, it has been demonstrated that the supramolecular chirality was directly dictated by the orientation of single ß strand. The insertion of glycine residue demolished the effect of lysine residues on the single strand conformation due to its high conformational flexibility. The replacement of L-isoleucine with Da-isoleucine also confirmed that the isoleucine residues involved in the ß-sheet determined the supramolecular handedness. This study provides a profound mechanism of the chiral self-assembly of short peptides. We hope that it will improve the regulation of chiral molecular self-assembly with achiral glycine, as well.

Effect of Iron Tailing Powder-Based Ternary Admixture on Acid Corrosion Resistance of Concrete.

Exposure of concrete to acidic environments can cause the degradation of concrete elements and seriously affect the durability of concrete. As solid wastes are produced during industrial activity, ITP (iron tailing powder), FA (fly ash), and LS (lithium slag) can be used as admixtures to produce concrete and improve its workability. This paper focuses on the preparation of concrete using a ternary mineral admixture system consisting of ITP, FA, and LS to investigate the acid erosion resistance of concrete in acetic acid solution at different cement replacement rates and different water-binder ratios. The tests were performed by compressive strength analysis, mass analysis, apparent deterioration analysis, and microstructure analysis by mercury intrusion porosimetry and scanning electron microscopy. The results show that when the water-binder ratio is certain and the cement replacement rate is greater than 16%; especially at 20%, the concrete shows strong resistance to acid erosion; when the cement replacement rate is certain and the water-binder ratio is less than 0.47; especially at 0.42, the concrete shows strong resistance to acid erosion. Microstructural analysis shows that the ternary mineral admixture system composed of ITP, FA, and LS promotes the formation of hydration products such as C-S-H and AFt, improves the compactness and compressive strength of concrete, and reduces the connected porosity of concrete, which can obtain good overall performance. In general, concrete prepared with a ternary mineral admixture system consisting of ITP, FA, and LS has better acid erosion resistance than ordinary concrete. The use of different kinds of solid waste powder to replace cement can effectively reduce carbon emissions and protect the environment.

FePSe3 -Nanosheets-Integrated Cryogenic-3D-Printed Multifunctional Calcium Phosphate Scaffolds for Synergistic Therapy of Osteosarcoma.

Clinical treatment of osteosarcoma encounters great challenges of postsurgical tumor recurrence and extensive bone defect. To develop an advanced artificial bone substitute that can achieve synergistic bone regeneration and tumor therapy for osteosarcoma treatment, a multifunctional calcium phosphate composite enabled by incorporation of bioactive FePSe3 -nanosheets within the cryogenic-3D-printed α-tricalcium phosphate scaffold (TCP-FePSe3 ) is explored. The TCP-FePSe3 scaffold exhibits remarkable tumor ablation ability due to the excellent NIR-II (1064 nm) photothermal property of FePSe3 -nanosheets. Moreover, the biodegradable TCP-FePSe3 scaffold can release selenium element to suppress tumor recurrence by activating of the caspase-dependent apoptosis pathway. In a subcutaneous tumor model, it is demonstrated that tumors can be efficiently eradicated via the combination treatment with local photothermal ablation and the antitumor effect of selenium element. Meanwhile, in a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by TCP-FePSe3 scaffold have been observed in vivo. The TCP-FePSe3 scaffold possesses improved capability to promote the repair of bone defects via vascularized bone regeneration, which is induced by the bioactive ions of Fe, Ca, and P released during the biodegradation of the implanted scaffolds. The TCP-FePSe3 composite scaffolds fabricated by cryogenic-3D-printing illustrate a distinctive strategy to construct multifunctional platform for osteosarcoma treatment.

Real-world comprehensive diagnosis and "Surgery + X" treatment strategy of early-stage synchronous multiple primary lung cancer.

BACKGROUND: Diagnosing and treating synchronous multiple primary lung cancers (sMPLC) are complex and challenging. This study aimed to report real-world data on the comprehensive diagnosis and treatment of patients with early-stage sMPLC. MATERIALS AND METHODS: A single-center cohort study was carried out and a large number of patients with early-stage sMPLC were included. A single- or two-stage surgery was performed to remove the primary and co-existing lesions. The "X" strategies, including ablation, SBRT, and EGFR-TKIs treatment, were applied to treat the high-risk residual lesions. Wide panel-genomic sequencing was performed to assess the genetic heterogeneity of the co-existing lesions. RESULTS: A total of 465 early-stage sMPLC patients with 1198 resected lesions were included. Despite most patients being histologically different or harboring different genetic alternations, about 7.5% of the patients had the same histological type and driver gene mutation changes, comprehensive re-evaluation is thus needed. The "Surgery + X" strategy showed remarkable efficacy and safety in treating multiple lesions. Follow-up data revealed that the T2 stage (p = 0.014) and the solid presence of a primary lesion (p < 0.001) were significantly related to tumor recurrence. And a T2-stage primary tumor had a significantly higher rate of developing new lesions after the initial surgery (p < 0.001). CONCLUSIONS: In real-world practice, histopathological and radiological evaluation combined with genetic analyses could be a robust diagnostic approach for sMPLC. The "Surgery + X" treatment strategy showed remarkable efficacy, superiority, and safety in the clinical treatment of early-stage sMPLC.

AhR Promotes the Development of Non-small cell lung cancer by Inducing SLC7A11-dependent Antioxidant Function.

Objective: Aryl hydrocarbon receptor (AhR) is a transcription factor. It is reported that AhR is associated with non-small cell lung cancer (NSCLC), but the mechanisms underlying this relationship remain unclear. Therefore, we investigated the role of AhR in NSCLC to elucidate the underlying mechanisms. Methods: We collected clinical lung cancer samples and constructed AhR overexpression and knockdown cell lines to investigate the tumorigenicity of AhR in vivo and in vitro. Furthermore, we performed a ferroptosis induction experiment and chromatin immunoprecipitation experiment. Results: AhR was highly expressed in NSCLC tissue. AhR knockdown cells showed ferroptosis related phenomenon. Furthermore, Chromatin immunoprecipitation confirmed the correlation between AhR and solute carrier family 7 member 11 (SLC7A11) and ferroptosis induction experiment confirmed that AhR affects ferroptosis via SLC7A11. Specifically, AhR regulates ferroptosis-related SLC7A11, which affects ferroptosis and promotes NSCLC progression. Conclusions: AhR promoted NSCLC development and positively correlated with SLC7A11, affecting its actions. AhR bound to the promoter region of SLC7A11 promotes NSCLC by activating SLC7A11 expression, improving the oxidative sensitivity of cells, and inhibiting ferroptosis. Thus, AhR affects ferroptosis in NSCLC by regulating SLC7A11, providing foundational evidence for novel ferroptosis-related treatments.

Prognostic value of perineural invasion in resected non-small cell lung cancer: A meta-analysis.

Objective: The prognostic role of perineural invasion (PNI) in resected non-small cell lung cancer (NSCLC) remains unclear. A meta-analysis was performed to compare the overall survival (OS) of patients with resected NSCLC with and without PNI. Methods: The PubMed, EMBASE, and Web of Science databases were systematically searched to identify relevant studies investigating the effect of PNI on OS in patients with resected NSCLC. Pooled hazard ratio (HR) and 95% confidence intervals (CI) were estimated using a random-effects model. Separate meta-analyses using adjusted or unadjusted HR for OS were performed using Stata/SE 12.0. Results: Eleven studies comprising 2,279 patients were included. In total, PNI was identified in 9% (median, 4%-31%) of patients with resected NSCLC. The unadjusted pooled effect of the PNI was significantly associated with worse OS (HR, 2; 95% CI, 1.65-2.43). Adjusting for potential confounders yielded a similar result, with OS being significantly worse (HR, 2.13; 95% CI, 1.8-2.51) for patients exhibiting PNI. Conclusion: This meta-analysis indicates that the PNI is a strong prognostic factor for unfavorable outcomes in patients with resected NSCLC. Further large-scale prospective lung cancer trials are required to validate these results.

Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer.

BACKGROUND: To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment. METHODS: Hundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups. RESULTS: Lesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups. CONCLUSION: Our study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC.

Black Silver Nanocubes@Amino Acid-Encoded Highly Branched Gold Shells with Efficient Photothermal Conversion for Tumor Therapy.

Cancers are among the leading causes of death currently. Conventional radiotherapy and chemotherapy are of limited use in the treatment of some tumors due to their high toxicity and drug resistance. Plasma photothermal therapy has attracted extensive attention for the treatment of tumors due to photothermal properties of plasmonic nanoparticles, such as gold (Au) nanoparticles, to achieve local hyperthermia with low toxicity and high efficiency. Herein, we report a kind of special black noble-metal core-shell nanostructure, with silver (Ag) nanocubes as the core and amino acid-encoded highly branched Au nanorods as the shells (l-CAg@Au and d-CAg@Au). The proposed growth of l-CAg@Au and d-CAg@Au nanocomposites was an amino acid-encoded Stranski-Krastanov mode. Both l-CAg@Au and d-CAg@Au exhibited outstanding photothermal conversion compared to the core-shell structure without amino acids (Ag@Au). d-CAg@Au possessed the best photothermal conversion efficiency (87.28%) among the composite nanoparticles. The antitumor therapeutic efficacy of as-prepared samples was evaluated in vitro and in vivo, and apoptosis analysis was done via flow cytometry. This work reports novel insights for the preparation of special bimetallic branched structures and broadens the application of metal nanomaterials in photothermal tumor therapy.

Rational design of graphite carbon nitride-decorated zinc oxide nanoarrays on three-dimensional nickel foam for the efficient production of reactive oxygen species through stirring-promoted piezo-photocatalysis.

Stirring-promoted piezo-photocatalysis based on a three-dimensional foam architecture has great potential applications in wastewater treatment and water splitting. However, the detailed mechanism of stirring-promoted piezo-photocatalysis has not been quantitatively studied, and the utilization of visible light needs to be further improved. In this work, the high solar-driven piezo-photocatalytic ability of graphite carbon nitride (g-C3N4)-decorated zinc oxide (ZnO) nanoarrays on nickel (Ni) foam is experimentally achieved and first simulated by the finite element method (FEM). The water flow velocity, depending on the stirring rate, is significantly increased by turbulence-induced fluid eddies while flowing through 3D macropores and nanoarrays, resulting in higher piezoelectricity. Reactive oxygen species (ROS) are experimentally examined by the electron spin resonance (ESR) technique and theoretically calculated by density functional theory (DFT) to confirm the configurations of the heterojunction under photocatalysis and piezo-photocatalysis. In particular, the large enhancement of 1O2 generation suggests the potential of piezo-photocatalysis in biological applications. The mechanism of piezo-photocatalysis is proposed in which the S-scheme heterojunction is realized by piezoelectricity to improve photocatalysis by retaining high redox ability and inhibiting recombination. This work provides a possible approach to harvesting energy sources for piezoelectricity and expands the scope of solar-driven piezo-photocatalysis.

Neoadjuvant targeted therapy for resectable EGFR-mutant non-small cell lung cancer: Current status and future considerations.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) targeted therapy has become the standard of care for patients with EGFR-mutated metastatic non-small cell lung cancer (NSCLC) on the basis of improved prognosis and reduced toxicities compared with chemotherapy. In view of the therapeutic potential of EGFR-TKIs in EGFR-mutated advanced NSCLC, several scholars have explored the value of preoperative use of EGFR-TKIs in patients with EGFR-mutated resectable NSCLC. However, the field of neoadjuvant targeted therapy for EGFR-mutated resectable NSCLC is currently in its infancy. In this mini-review, we summarize the current evidence on neoadjuvant EGFR-TKIs targeted therapy for resectable EGFR-mutated NSCLC and focus on discussing potential clinical strategies of treating resectable EGFR-mutated patients by preoperative administration of EGFR-TKIs-based multimodality therapy.

Comprehensive characterization of genomic and radiologic features reveals distinct driver patterns of RTK/RAS pathway in ground-glass opacity pulmonary nodules.

Ground-glass opacity (GGO)-associated pulmonary nodules have been known as a radiologic feature of early-stage lung cancers and exhibit an indolent biological behavior. However, the correlation between driver genes and radiologic features as well as the immune microenvironment remains poorly understood. We performed a custom 1021-gene panel sequencing of 334 resected pulmonary nodules presenting as GGO from 262 Chinese patients. A total of 130 multiple pulmonary nodules were sampled from 58 patients. Clinical-pathologic and radiologic parameters of these pulmonary nodules were collected. Immunohistochemistry (IHC) and multiplex immunofluorescent staining (mIF) were applied to analyze proliferation and immune cell markers of GGO-associated pulmonary nodules. Compared with pure GGO nodules, mixed GGO nodules were enriched for invasive adenocarcinoma (IAC) (182/216 vs 73/118, P < .001). Eighty-eight percent (294/334) of GGO-associated nodules carried at least one mutation in EGFR/ERBB2/BRAF/KRAS/MAP2K1 of the RTK/RAS signaling pathway, and the alterations in these driver genes were mutually exclusive. The analysis of multifocal pulmonary nodules from the same patient revealed evidence of functional convergence on RTK/RAS pathways. Nodules with ERBB2/BRAF/MAP2K1 mutations tended to be more indolent than those with EGFR and KRAS mutations. IHC and mIF staining showed that KRAS-mutant GGO nodules displayed higher infiltration of CD4+ T cell and CD8+ T cell as well as stronger proliferation and immune inhibitory signals. Our study demonstrates a driver landscape of radiologically detectable GGO-associated pulmonary nodules in Chinese patients and supports that different driver patterns in RTK/RAS pathway are corresponding to different radiologic features.

Case Report: Pathological Complete Response to Neoadjuvant Alectinib in a Patient With Resectable ALK-Positive Non-Small Cell Lung Cancer.

Background: Alectinib, a highly selective inhibitor of ALK, is currently used in the first-line setting of untreated advanced ALK-positive NSCLC and in the second-line setting of crizotinib-resistant ALK-positive NSCLC. Despite promising efficacy and tolerability in the treatment of advanced ALK-positive NSCLC, the activity of alectinib as neoadjuvant therapy in resectable ALK-positive NSCLC remains to be investigated. Case presentation: Herein, we report a case of a 58-year-old female patient presented to our hospital with hemoptysis for 1 month. Contrast-enhanced computerized tomography (CT) of the chest showed an approximately 4.2 × 3.4 cm mass in the right hilum with localized obstructive pneumonia in the right lower lobe and multiple enlarged lymph nodes in the right hilum and mediastinum. Serum oncological markers results showed elevated levels of CA19-9, CEA, CA125, and CA242. Bronchoscopic biopsy of the mass showed poorly differentiated pulmonary adenocarcinoma and immunohistochemical testing results confirmed ALK positivity. Neoadjuvant alectinib was given at a dosage of 600 mg twice per day for two cycles (56 days), achieving a partial response of the disease with 90% shrinkage of the mass at the subsequent whole-body positron emission tomography. Repeat serum oncological markers results showed that only CA125 was elevated, but lower than before therapy. A bilobectomy of the right middle and lower lobes and systemic lymphadectomy under video-assisted thoracoscopic approach was successfully performed 7 days after the last dose of alectinib. Postoperative pathology showed pathological complete response (pCR). The patient experienced an uneventful postoperative course and continued to receive alectinib and did not report any specific discomfort at her 8-month follow-up. Thoracoabdominal CT at 8 months postoperatively showed no recurrence and repeated examination of serum oncological markers were negative. Conclusion: We report a case of resectable ALK-positive NSCLC treated with neoadjuvant aletinib achieving pCR. Our case highlights the feasibility of alectinib as neoadjuvant therapy for the treatment of resectable ALK-positive NSCLC. Undoubtedly, the safety and efficacy of this novel treatment modality needs to be explored in future large clinical trials.

[In Vitro Fatigue Test of Lung Volume Reduction Loop].

Lung volume reduction loop uses bronchoscopic lung volume reduction(BLVR) technology to compress and collapse the necrotic emphysema tissue and exhaust the internal gas to achieve the purpose of lung volume reduction to treat emphysema. After the lung volume reduction loop is implanted into the human body, the compressed part of the lung tissue tends to expand with breathing, which makes the lung volume reduction loop expand into a linear trend periodically. Fatigue resistance is one of the most important performance indexes of the lung volume reduction loop. In the paper, Z-direction vibration fatigue machine was used to simulate the changes of human respiratory cycle movement to test the fatigue performance of lung volume reduction loop, which can provide some reference for the test method of in vitro fatigue performance of lung volume reduction related products in the future.