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Abstract Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.

Objective This study aimed to explore decision‐making impulsivity and its neural mechanisms in patients with episodic migraine without aura (EMoA). Background Previous evidence indicates increased impulsivity and altered reward processing in patients with chronic migraine and medication overuse; however, whether the same holds true for those with EMoA is unclear. Methods Patients newly diagnosed with EMoA (n = 51) and healthy controls (HC, n = 45) were recruited. All participants completed delay discounting task, cognitive assessments, a questionnaire for headache profile, and resting‐state function magnetic resonance imaging scans. Resting‐state functional connectivity (RSFC) between the regions of interest and the entire brain was explored. Results Patients with EMoA showed a steeper subjective discount rate than HCs (F = 4.74, p = .032), which was positively related to a history of migraines (r = .742, p

River corridors, recognized as “blue–green infrastructure,” have become a crucial support system for urban sustainability in contemporary urbanized societies. Understanding the factors influencing the recreational experience along urban river corridors is paramount for enhancing visitors’ health and well-being. This study focuses on the Hutuo River Corridor in Shijiazhuang, China, collecting 3006 valid reviews from Dianping, a prominent review platform. We developed a text-based thematic model and conducted content analysis using this dataset. The main social (visiting time, duration of stay, motivation, safety, and visitors’ types and activities) and physical (natural elements, artificial facilities, maintenance and management, accessibility, distance, models of transportation, weather, and seasons) factors associated with recreational experiences were identified. We assessed visitor perceptions of urban river corridors and elucidated facilitators or barriers through textual content analysis in reviews. The results indicate the feasibility of employing social media data to study visitors’ recreational experiences along urban river corridors. This comprehensive exploration from a qualitative ecological perspective contributes valuable insights for urban planning and management. Moreover, the findings hold significant implications for understanding the usage patterns of river corridors in China and potentially in other countries.

To address the issue of soil erosion and limited economically valuable vegetation resources, perennial sweet peas were introduced to Hebei Province, China, and showed favorable biological attributes. Nevertheless, its specific efficacy within soil and water conservation endeavors requires further examination. This study selected four trial sites within Hebei Province to assess four-year-old perennial sweet peas’ soil and water conservation functionality. The findings underscored that cultivating perennial sweet pea plots on 9° disturbed slopes notably outperformed bare ground (CK) in their rainwater absorption capacity. Specifically, in the 0–20 cm soil layer, moisture increased from 10.51% to 17.39%, in the 20–40 cm layer from 10.63% to 17.25%, and in the 40–60 cm layer from 10.09% to 16.04%. The dense canopy formed by perennial sweet peas effectively intercepted 25–32% of precipitation. Fallen organic matter also demonstrated commendable water absorption features. During severe rain, the perennial sweet pea showcased a 90.4% runoff reduction and a notable sediment interception. Their deep and well-developed root system enhanced soil structure and infiltration. The outcomes of this study highlight the perennial sweet peas’ potential in soil erosion mitigation, rainwater retention, and soil improvement, which carries substantial implications for sustainable land management and ecosystem restoration initiatives. Furthermore, the successful introduction of perennial sweet peas could serve as a model for analogous ecological interventions in regions confronting similar challenges, offering holistic solutions to soil and water conservation in environmentally sensitive areas.

The aim of this work is the preliminary clinical validation and accuracy evaluation of our automatic algorithms in assessing progression fetal femur length (FL) in ultrasound images. To compare the random forest regression model with the SegNet model from the two aspects of accuracy and robustness. In this study, we proposed a traditional machine learning method to detect the endpoints of FL based on a random forest regression model. Deep learning methods based on SegNet were proposed for the automatic measurement method of FL, which utilized skeletonization processing and improvement of the full convolution network. Then the automatic measurement results of the two methods were evaluated quantitatively and qualitatively with the results marked by doctors. 436 ultrasonic fetal femur images were evaluated by the two methods above. Compared the results of the above three methods with doctor's manual annotations, the automatic measurement method of femur length based on the random forest regression model was 1.23 ± 4.66 mm and the method based on SegNet was 0.46 ± 2.82 mm. The indicator for evaluating distance was significantly lower than the previous literature. Measurement method based SegNet performed better in the case of femoral end adhesion, low contrast, and noise interference similar to the shape of the femur. The segNet-based method achieves promising performance compared with the random forest regression model, which can improve the examination accuracy and robustness of the measurement of fetal femur length in ultrasound images.

BackgroundThe recognition of anatomical variants is essential in preoperative planning for lung cancer surgery. Although three-dimensional (3-D) reconstruction provided an intuitive demonstration of the anatomical structure, the recognition process remains fully manual. To render a semiautomated approach for surgery planning, we developed an artificial intelligence (AI)–based chest CT semantic segmentation algorithm that recognizes pulmonary vessels on lobular or segmental levels. Hereby, we present a retrospective validation of the algorithm comparing surgeons’ performance.MethodsThe semantic segmentation algorithm to be validated was trained on non-contrast CT scans from a single center. A retrospective pilot study was performed. An independent validation dataset was constituted by an arbitrary selection from patients who underwent lobectomy or segmentectomy in three institutions during Apr. 2020 to Jun. 2021. The golden standard of anatomical variants of each enrolled case was obtained via expert surgeons’ judgments based on chest CT, 3-D reconstruction, and surgical observation. The performance of the algorithm is compared against the performance of two junior thoracic surgery attendings based on chest CT.ResultsA total of 27 cases were included in this study. The overall case-wise accuracy of the AI model was 82.8% in pulmonary vessels compared to 78.8% and 77.0% for the two surgeons, respectively. Segmental artery accuracy was 79.7%, 73.6%, and 72.7%; lobular vein accuracy was 96.3%, 96.3%, and 92.6% by the AI model and two surgeons, respectively. No statistical significance was found. In subgroup analysis, the anatomic structure-wise analysis of the AI algorithm showed a significant difference in accuracies between different lobes (p = 0.012). Higher AI accuracy in the right-upper lobe (RUL) and left-lower lobe (LLL) arteries was shown. A trend of better performance in non-contrast CT was also detected. Most recognition errors by the algorithm were the misclassification of LA1+2 and LA3. Radiological parameters did not exhibit a significant impact on the performance of both AI and surgeons.ConclusionThe semantic segmentation algorithm achieves the recognition of the segmental pulmonary artery and the lobular pulmonary vein. The performance of the model approximates that of junior thoracic surgery attendings. Our work provides a novel semiautomated surgery planning approach that is potentially beneficial to lung cancer patients.

Species within the Aspergillus spp. cause a wide range of infections in humans, including invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis, and are associated with high mortality rates. The incidence of pulmonary aspergillosis (PA) is on the rise, and the emergence of triazole-resistant Aspergillus spp. isolates, especially Aspergillus fumigatus, limits the efficacy of mold-active triazoles. Therefore, host-directed and novel adjunctive therapies are required to more effectively combat PA. In this review, we focus on PA from a microbiome perspective. We provide a general overview of the effects of the lung and gut microbiomes on the growth of Aspergillus spp. and host immunity. We highlight the potential of the microbiome as a therapeutic target for PA.

Background. Lung adenocarcinoma is one of the most commonly diagnosed malignancies worldwide. Macrophage plays crucial roles in the tumor microenvironment, but its autocrine network and communications with tumor cell are still unclear. Methods. We acquired single-cell RNA sequencing (scRNA-seq) (n=30) and bulk RNA sequencing (n=1480) samples of lung adenocarcinoma patients from previous literatures and publicly available databases. Various cell subtypes were identified, including macrophages. Differentially expressed ligand-receptor gene pairs were obtained to explore cell-to-cell communications between macrophages and tumor cells. Furthermore, a machine-learning predictive model based on ligand-receptor interactions was built and validated. Results. A total of 159,219 single cells (18,248 tumor cells and 29,520 macrophages) were selected in this study. We identified significantly correlated autocrine ligand-receptor gene pairs in tumor cells and macrophages, respectively. Furthermore, we explored the cell-to-cell communications between macrophages and tumor cells and detected significantly correlated ligand-receptor signaling pairs. We determined that some of the hub gene pairs were associated with patient prognosis and constructed a machine-learning model based on the intercellular interaction network. Conclusion. We revealed significant cell-to-cell communications (both autocrine and paracrine network) within macrophages and tumor cells in lung adenocarcinoma. Hub genes with prognostic significance in the network were also identified.

Landscape preference and cognition are essential in determining the external environment’s subjective reflections. Although much research has been conducted on landscape preferences, there is still a lack of information on landscape perceptions and preferences among residents of disadvantaged neighbourhoods, especially in Chinese cities. Taking old residential neighbourhoods of Shijiazhuang as an example, this paper used a large-scale questionnaire survey and semi-structured interviews to determine the landscape preference of the residents of old residential neighbourhoods for the community green spaces using the virtual model method. The chi-square test method is used to explore the inner logic of aesthetic preference from two aspects: landscape characteristics and socio-demographic characteristics. The respondents are 668 residents of old residential neighbourhoods (300 males, 368 females) distributed in four larger communities in the main urban area of Shijiazhuang. Random sampling and volunteer sampling were used to choose the survey respondents. The results showed this: (1) In terms of soft landscapes, respondents prefer natural planting, spaces with very high plant richness and high green coverage. In terms of hard landscapes, there is a preference for fitness and leisure facilities, rubber floors and a slight preference for water features and decorative landscape elements. (2) From the chi-square results, age significantly affects landscape preference, gender and education level. In contrast, marital status and occupation have no significant effect on landscape preference. The expression of the landscape preference of the residents of old residential neighbourhoods reflects the needs for functionality, reality and local concept. The main aim of this study is to fully understand the landscape preferences of residents in old residential neighbourhoods when using green space, and to find out what factors will affect residents’ landscape preferences. The research results have guiding significance for rationally improving the landscape planning, design and management of old residential neighbourhoods, and at the same time make up for the lack of international research on landscape preferences of disadvantaged communities. Improving the environment of old residential neighbourhoods can develop a higher sense of security, happiness and satisfaction among the residents.

Studies have shown that disadvantaged neighborhoods have fewer green spaces, resources, and facilities, resulting in residents facing more barriers to using green spaces. This study aims to quantify green space usage patterns and constraints in old residential neighborhoods in a large city in northern China. A questionnaire survey and semi-structured interviews were conducted with 668 residents. Results showed that most residents visited their local green spaces daily, often in the evenings, and spent between 30 and 60 min there. The number of visits on weekends is higher than on weekdays, with no difference in visiting alone or in groups. The main reason for visiting green spaces was to relax and enjoy nature, followed by spending time with family. Limitations to usage included poor physical environments, such as inadequate facilities, lack of maintenance, overcrowding, poor accessibility, limited activities, and pet restrictions. This study provides insights into the current state of green space utilization in old residential neighborhoods, as well as a discussion of the limitations, which could inform future renovations and designs of green spaces in these areas.

Bioluminescent tomography (BLT) has increasingly important applications in preclinical studies. However, the simplified photon propagation model and the inherent ill-posedness of the inverse problem limit the quality of BLT reconstruction. In order to improve the reconstruction accuracy of positioning and reconstruction efficiency, this paper presents a deep-learning optical reconstruction method based on one-dimensional convolutional neural networks (1DCNN). The nonlinear mapping relationship between the surface photon flux density and the distribution of the internal bioluminescence sources is directly established, which fundamentally avoids solving the ill-posed inverse problem iteratively. Compared with the previous reconstruction method based on multilayer perceptron, the training parameters in the 1DCNN are greatly reduced and the learning efficiency of the model is improved. Simulations verify the superiority and stability of the 1DCNN method, and the in vivo experimental results further show the potential of the proposed method in practical applications.

Background: Despite decades of intense research, the pathophysiology and pathogenesis of acute respiratory distress syndrome (ARDS) are not adequately elucidated, which hamper the improvement of effective and convincing therapies for ARDS patients. Mechanical ventilation remains to be one of the primary supportive approaches for managing ARDS cases. Nevertheless, mechanical ventilation leads to the induction of further aggravating lung injury which is known as leading to ventilator-induced lung injury (VILI). It has been reported that lncRNAs play important roles in various cellular process through transcriptional, posttranscriptional, translational, and epigenetic regulations. However, to our knowledge, there is no investigation of the expression profile and functions of transcriptome-level endothelium-related lncRNAs in VILI yet.Methods: To screen the differential expression of lncRNAs and mRNAs in Human pulmonary microvascular endothelial cells (HPMECs) subjected to cyclic stretch, we constructed a cellular model of VILI, followed by transcriptome profiling using Affymetrix Human Transcriptome Array 2.0. Bioinformatics analyses, including functional and pathway enrichment analysis, protein–protein interaction network, lncRNA-mRNA coexpression network, and cis-analyses, were performed to reveal the potential functions and underlying mechanisms of differentially expressed lncRNAs.Results: In total, 199 differentially expressed lncRNAs (DELs) and 97 differential expressed mRNAs were screened in HPMECs subjected to 20% cyclic stretch for 2 h. The lncRNA-mRNA coexpression network suggested that DELs mainly enriched in response to hypoxia, response to oxidative stress, inflammatory response, cellular response to hypoxia, and NF-kappa B signaling pathway. LncRNA n335470, n406639, n333984, and n337322 might regulate inflammation and fibrosis induced by cyclic stretch through cis- or trans-acting mechanisms.Conclusion: This study provides the first transcriptomic landscape of differentially expressed lncRNAs in HPMECs subjected to cyclic stretch, which provides novel insights into the molecular mechanisms and potential directions for future basic and clinical research of VILI.

BackgroundWe investigated the prognostic effects and their patterns of immune infiltration of hippo pathway core genes in lung squamous cell carcinoma, in order to find some clues for underlying mechanisms of LUSC tumorigenesis and help developing new therapeutic methods.MethodsThe mutational data, transcriptome data and corresponding clinical medical information of LUSC patients were extracted from The Cancer Genome Atlas (TCGA) database. Differential expression genes (DEGs) and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were explored. Survival analysis for the hippo core genes and the prognostic model were performed. Immune infiltration was estimated by CIBERSORT algorithm and some immune checkpoints-related genes were further investigated.ResultsOverall, 551 LUSC samples were included in our study, consisting of 502 LUSC tumor samples and 49 adjacent normal samples, respectively. There were 1910 up-regulated DEGs and 2253 down-regulated DEGs were finally identified. The top five mutational hippo pathway core genes were LATS1 (4%), WWC1 (2%), TAOK1 (2%), TAOK3 (2%), and TAOK2 (2%), respectively. the mutation of LATS2 was highly associated with co-mutational NF2 (P

BackgroundTumor spread through air spaces (STAS) has three morphologic subtypes: single cells, micropapillary clusters, and solid nests. However, whether their respective clinical significance is similar remains unclear.MethodsWe retrospectively reviewed 803 patients with resected non-small cell lung cancer (NSCLC) from January to December 2009. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS subtypes. We also performed a prospective study of NSCLC resection specimens to evaluate the influence of a prosecting knife on the presence of STAS subtypes during specimen handling (83 cases).ResultsSTAS was found in 370 NSCLCs (46%), including 47 single cell STAS (13%), 187 micropapillary cluster STAS (50%), and 136 solid nest STAS (37%). STAS-negative patients had significantly better survival than patients with micropapillary cluster STAS (RFS: P < 0.001; OS: P < 0.001) and solid nest STAS (RFS: P < 0.001; OS: P < 0.001), but similar survival compared with those with single cell STAS (RFS: P = 0.995; OS: P = 0.71). Multivariate analysis revealed micropapillary cluster (RFS: P < 0.001; OS: P < 0.001) and solid nest STAS (RFS: P = 0.001; OS: P = 0.003) to be an independent prognostic indicator, but not for single cell STAS (RFS: P = 0.989; OS: P = 0.68). Similar results were obtained in subgroup analysis of patients with adenocarcinoma. The prospective study of NSCLC specimens suggested that 18 cases were considered as STAS false-positive, and most were singe cell pattern (13/18, 72%).ConclusionsSingle cell STAS was the common morphologic type of artifacts produced by a prosecting knife. A precise protocol of surgical specimen handling is required to minimize artifacts as much as possible.

Background: Our aim was to investigate the prognostic impact of the lepidic component on T stage in patients with lung adenocarcinoma (LUAD). Methods: A retrospective data set including 863 cases of LUAD with lepidic component and 856 cases without lepidic component was used to identify matched lepidic-positive and lepidic-negative cohorts ( n = 376 patients per group) using a propensity-score matching. Primary outcome variables included recurrence-free survival (RFS) and overall survival (OS). Prognostic factors were assessed by Cox regression analysis and Kaplan–Meier estimates. Results: Multivariate analysis revealed that lepidic component presence was an independent prognostic factor for prolonged RFS ( p 25% or ⩽25% were confirmed to be independent prolonged survival predictors. No survival differences were observed between patients with LUAD with LR >25% or ⩽25% (RFS p = 0.333; OS p = 0.078). The 5-year OS rates of patients with LUAD with a lepidic component were 90% regardless of the T stage, and these survival rates were significantly better than those of patients with LUAD without a lepidic component in the corresponding T stage. Multivariate analysis confirmed that T stage was associated with survival only in patients with LUAD without a lepidic component. Conclusions: Lepidic component presence identifies a LUAD subgroup with an excellent prognosis independent of the LR, pathological T classification. Considering the lepidic component presence may improve prognostic predictions for patients with LUAD.

N6-Methyladenosine (m6A) RNA modification brings a new dawn for RNA modification researches in recent years. This posttranscriptional RNA modification is dynamic and reversible, and is regulated by methylases (“writers”), demethylases (“erasers”), and proteins that preferentially recognize m6A modifications (“readers”). The change of RNA m6A modification regulates RNA metabolism in eucaryon, including translation, splicing, exporting, decay, and processing. Thereby the dysregulation of m6A may lead to tumorigenesis and progression. Given the tumorigenic role of abnormal m6A expression, m6A regulators may function as potential clinical therapeutic targets for cancers. In this review, we emphasize on the underlying mechanisms of m6A modifications in tumorigenesis and further introduce the potential m6A regulators-associated therapeutic targets for tumor therapy.

Aims: Interstitial lung disease (ILD) is associated with the incidence of non-small cell lung cancer (NSCLC). Patients with ILD are at risk of acute exacerbation (AE) after pulmonary resection. However, there have been no recognized treatment guidelines for NSCLC patients with ILD on computed tomography (CT). Methods: We reviewed the medical records of 156 consecutive patients with ILD on high-resolution CT who have undergone pulmonary resection and between 2014 and 2018. Data regarding general information, imaging features, perioperative indicators, and long-term prognosis of patients were compared. Results: The mean patient age was 67.24 ± 6.80 years. Postoperative AE occurred in seven (4.5%) patients; five (71.4%) of the seven patients who had an AE died within 30 days. The incidence of postoperative AE was 5.3% among patients who underwent lobectomy ( n = 6). Overall survivals (OS) was significantly poorer in patients with possible usual interstitial pneumonia (UIP)/UIP [hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.11–4.95, p = 0.026] and severe postoperative complications (Grade ⩾3) ( versus no complication: HR 2.58, 95% CI 1.11–6.02, p = 0.028; versus mild complications: HR 6.05, 95% CI 2.69–13.6, p

Background: Limited resection has gradually become an acceptable treatment for lung adenocarcinomas (ADCs) presenting as ground-glass nodules (GGNs). However, its role in lung ADCs presenting as pure solid nodules (PSN) remains unclear. In this study, we aimed to identify potential candidates for limited resection in lung ADCs presenting as PSN. Methods: We retrospectively reviewed 772 patients from seven hospitals with lung ADCs ⩽2 cm, presenting as PSN on computed tomography scans, who had undergone surgery between 2009 and 2013. Histological subtypes were listed in 5% increments. To investigate the value of histological subtypes in surgical decision making, five pathologists prospectively evaluated the feasibility of identifying histological subtypes using frozen section (FS) in two cohorts. Results: The percentage of micropapillary (MIP) subtype had a striking impact on recurrence-free survival (RFS) and overall survival (OS) for lung ADCs ⩽2 cm presenting as PSNs. In multivariable Cox analysis, segmentectomy was significantly associated with worse RFS and OS in patients with MIP >5% than lobectomy, but not in those with MIP ⩽5%. With wedge resection, worse RFS and OS were observed in patients with MIP >5% and those with MIP ⩽5% than lobectomy. The sensitivity and specificity for detecting MIP by FS were 74.2% and 85.6%, respectively, with substantial inter-rater agreement. Conclusion: Segmentectomy and lobectomy had similar oncological outcomes in patients with lung ADCs ⩽2 cm presenting as PSN with MIP ⩽5%. Randomized trials are necessary to validate the feasibility of intraoperative FS to choose candidates for segmentectomy.

Objective. Selenium, as an antioxidant, has been implicated in the development of autoimmune thyroiditis (AIT). Many studies showed selenium supplementation could decrease thyroid autoantibodies in patients with AIT. However, the underlying mechanisms have not been well determined. Therefore, we performed a clinical study to investigate the possible mechanism of beneficial effects of selenium treatment on AIT patients. Methods. Forty euthyroid patients with AIT were randomized into two groups. Group I was treated with 200 μg/day selenium supplementation, and group II received a placebo over a 3-month period. Thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TgAb), malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD) were measured before and 3 months after treatments. Additionally, twenty healthy volunteers also served as a control group for the evaluation of such parameters in basic condition. Results. Totally, 32 patients (group I, n = 18; group II, n = 14) completed the clinical study and were incorporated into the statistics. MDA level was higher and SOD activity and TAC were lower in patients compared to healthy individuals. After 3 months, TPOAb titer significantly decreased within group I (P0.05). Additionally, decreased MDA level (from 6.8 ± 1.3 nmol/ml to 4.9 ± 0.7 nmol/ml; P

Objective: Synchronous multiple ground-glass nodules (SM-GGNs) are a distinct entity of lung cancer which has been emerging increasingly in recent years in China. The oncogenesis molecular mechanisms of SM-GGNs remain elusive.Methods: We investigated single nucleotide variations (SNV), insertions and deletions (INDEL), somatic copy number variations (CNV), and germline mutations of 69 SM-GGN samples collected from 31 patients, using target sequencing (TRS) and whole exome sequencing (WES).Results: In the entire cohort, many known driver mutations were found, including EGFR (21.7%), BRAF (14.5%), and KRAS (6%). However, only one out of the 31 patients had the same somatic missense or truncated events within SM-GGNs, indicating the independent origins for almost all of these SM-GGNs. Many germline mutations with a low frequency in the Chinese population, and genes harboring both germline and somatic variations, were discovered in these pre-stage GGNs. These GGNs also bore large segments of copy number gains and/or losses. The CNV segment number tended to be positively correlated with the germline mutations (r = 0.57). The CNV sizes were correlated with the somatic mutations (r = 0.55). A moderate correlation (r = 0.54) was also shown between the somatic and germline mutations.Conclusion: Our data suggests that the precancerous unstable CNVs with potentially predisposing genetic backgrounds may foster the onset of driver mutations and the development of independent SM-GGNs during the local stimulation of mutagens.

Objective: The prognostic analysis of limited resection vs. lobectomy in stage IA small cell lung cancer (SCLC) remains scarce.Methods: Using the Surveillance, Epidemiology, and End Results registry (SEER) database, we identified patients who were diagnosed with pathological stage IA (T1a/bN0M0) SCLC from 2004 to 2013. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of patients with different treatment schemes were compared in stratification analyses. Univariable and multivariable analyses were also performed to identify the significant predictors of OS and LCSS.Results: In total, we extracted 491 pathological stage IA SCLC patients, 106 (21.6%) of whom received lobectomy, 70 (14.3%) received sublobar resection and 315 (64.1%) received non-surgical treatment, respectively. There were significant differences among the groups based on different treatment schemes in OS (log-rank p < 0.0001) and LCSS (log-rank p < 0.0001). Furthermore, in subgroup analyses, we did not identify any differences between sublober resection group and lobectomy group in OS (log-rank p = 0.14) or LCSS (log-rank p = 0.4565). Patients with four or more lymph node dissection had better prognosis. Multivariable analyses revealed age, laterality, tumor location, and N number were still significant predictors of OS, whereas age, tumor location, and N number were significant predictors of LCSS.Conclusion: Surgery is an important component of multidisciplinary treatment for stage IA SCLC patients and sublober resection is not inferior to lobectomy for the specific patients.

The aim of this study was to construct a rabbit anterior corneal replacement for transplantation using acellular porcine corneal matrix (APCM) and rabbit epithelial or stromal cells. APCM was prepared from fresh porcine cornea treated with 0.5% (wt./vol.) sodium dodecyl sulfate (SDS) solution. The expanded stromal cells were first injected into APCM parallel to its surface and were cultured in a shaking culture system for 7 days to obtain the stromal construct. Next, corneal epithelial cells were cultured on the stromal construct surface for another 7 days to obtain rabbit anterior corneal lamella. The construct had a phenotype similar to that of normal cornea, with high expression of cytokeratin 3 in the epithelial cell layer and vimentin in the stromal cells. More importantly, the construct integrated well with the implanted host corneal tissue, and the implant cornea maintained transparency in the 6-month follow-up, although there was a slight haze in the central corneal area. The endothelium in the surgery cornea had a similar cell density and mosaic pattern with normal cornea as shown by confocal laser corneal microscopy, and the regenerated corneal epithelial cells on the implant surface showed a similar morphology to that of natural epithelial cells. These results demonstrate that the constructed anterior corneal replacement exhibits an excellent biological property for lamellar keratoplasty and might be a possible alternative to human corneal tissue in the future.