Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The Astragalus-Coptis drug pair is frequently employed in the management of DKD. However, the precise molecular mechanism underlying its therapeutic effect remains elusive. AIM: To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways. METHODS: The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform. The targets were predicted using the SwissTargetPrediction database, while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database. DKD targets were acquired from the GeneCards, Online Mendelian Inheritance in Man database, and DisGeNET databases, with common targets identified through the Venny platform. The protein-protein interaction network and the "disease-active ingredient-target" network of the common targets were constructed utilizing the STRING database and Cytoscape software, followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients. Gene Ontology (GO) function and Kyoto Ency-clopedia of Genes and Genomes (KEGG) pathway enrichments were performed using the DAVID database. The tissue and organ distributions of key targets were evaluated. PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets. Finally, molecular dynamics (MD) simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins. RESULTS: A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified. There were 273 common targets between DKD and the Astragalus-Coptis drug pair. Through protein-protein interaction network topology analysis, we identified 9 core active ingredients and 10 key targets. GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes, including protein phosphorylation, negative regulation of apoptosis, inflammatory response, and endoplasmic reticulum unfolded protein response. These pathways are mainly associated with the advanced glycation end products (AGE)-receptor for AGE products signaling pathway in diabetic complications, as well as the Lipid and atherosclerosis. Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets. Notably, the quercetin-AKT serine/threonine kinase 1 (AKT1) and quercetin-tumor necrosis factor (TNF) protein complexes exhibited exceptional stability. CONCLUSION: This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients, targets, and signaling pathways. We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD. Furthermore, we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF, providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Comprehensive Analysis of a Dendritic Cell Marker Genes Signature to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma.

With the development of immune checkpoints inhibitors (ICIs), immunotherapy has recently taken center stage in cancer treatment. Dendritic cells exert complicated and important functions in antitumor immunity. This study aims to construct a novel dendritic cell marker gene signature (DCMGS) to predict the prognosis and immunotherapy response of lung adenocarcinoma (LUAD). DC marker genes in LUAD were identified by analysis of single-cell RNA sequencing data. 6 genes (G0S2, KLF4, ALDH2, IER3, TXN, CD69) were screened as the most prognosis-related genes for constructing DCMGS on a training cohort from TCGA data set. Patients were divided into high-risk and low-risk groups by DCMGS risk score based on overall survival time. Then, the predictive ability of the risk model was validated in 6 independent cohorts. DCMGS was verified to be an independent prognostic factor in multivariate analysis. Furthermore, we performed pathway enrichment analysis to explore possible biological mechanisms of the powerful predictive ability of DCMGS, and immune cell infiltration landscape and inflammatory activities were exhibited to reflect the immune profile. Notably, we bridged DCMGS with expression of immune checkpoints and TCR/BCR repertoire diversity that can inflect immunotherapy response. Finally, the predictive ability of DCMGS in immunotherapy response was also validated by 2 cohorts that had received immunotherapy. As a result, the patients with lower DCMGS risk scores showed a better prognosis and immunotherapy response. In conclusion, DCMGS was suggested to be a promising prognostic indicator for LUAD and a desirable predictor for immunotherapy response.

Identification of prognostic value of anoikis-related gene score model combined with tumor microenvironment score models in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has poor survival. Effective prognostic models with high application value remain lack. METHODS: Bulk RNA seq and single cell RNA-seq data were retrieved from the XENA-TCGA-ESCC cohort and GSE188900. The anoikis-related gene score (ANO score) model and tumor microenvironment score (TME score) model were constructed and merged into three subgroups. Functional annotation was analyzed by Gene Ontology terms. Univariate and multivariate Cox regression analysis, least absolute shrinkage and selection operator regression analysis and weighted gene coexpression network analysis were performed to construct prognostic prediction models and identify prognostic value. Kaplan-Meier survival curves were drawn for evaluating the overall survival (OS) of patients classified by different score subgroups. Immunotherapy response and mutation analyses were also conducted. RESULTS: In the ANO score model, TNFSF10 was an independent factor for the prognosis of ESCC patients. The area under the curve values of the ANO-TME score model in predicting the OS were 0.638 at 5 years and 0.632 at 7 years. Patients in the ANO low score-TME high score group had a much longer OS than patients in any other ANO-TME score subgroup (p < 0.001), suggesting a higher prognostic value. The differentially expressed genes of the ANO low score-TME high score group were mainly involved in cell adhesion molecules, nucleotide excision repair, the TGF-ß signaling pathway and mismatch repair. TP53 (92%), TTN (38%) and NFE2L2 (31%) were the top genes with highest mutant frequency in the ANO low score-TME high score group. CONCLUSIONS: A novel prognostic prediction model with high application value was constructed and identified for ESCC patients, which may provide evidence for immunotherapy in the treatment of ESCC.

COL3A1-positive endothelial cells influence LUAD prognosis and regulate LUAD carcinogenesis by NCL-PI3K-AKT axis.

BACKGROUND: Lung adenocarcinoma (LUAD), as the most common type of lung cancer, poses a significant threat to public health. Tumor heterogeneity plays a crucial role in carcinogenesis, which could be largely deciphered by next-generation sequencing (NGS). METHODS: We obtained and screened single-cell RNA sequencing (scRNA-seq) data from 16 LUAD samples, and endothelial cells (ECs) were grouped into three clusters. The origin of EC differentiation was explored by pseudo-time analysis. CellChat analysis was used to detect potential communication between ECs and malignant cells, and gene regulatory network analysis was used to identify changes in transcription factor activity. We explored the prognosis of specific ECs clusters and their effects on the tumor microenvironment (TME) at the bulk transcriptome level. 5-Ethynyl-2'- deoxyuridine (EdU) and Ki-67 staining were conducted to study the proliferative phenotype of LUAD cell lines. Western blotting targeting the phosphorylation of PI3K-AKT proteins was utilized for determination of the downstream pathway of NCL. RESULTS: COL3A1-positive ECs showed the highest crosstalk interaction with malignant cells, indicating that they have important effects on driving LUAD carcinogenesis. Vascular endothelial growth factor (VEGF) signaling pathway was identified as the main signaling pathway, mediating signal transduction from malignant cells. The TME-related genes of COL3A1-positive ECs were significantly more highly expressed. COL3A1-positive ECs showed unique metabolic and immune characteristics, as well as highly activated metabolic signaling pathways and inflammatory responses. Importantly, LUAD patients with low COL3A1-positive ECs scores displayed an inferior prognosis outcome and a higher risk of metastasis. The key target gene NCL, which is involved in the interaction between epithelial cells and cancer cells, has been identified through screening. Flow cytometry showed that knockdown of NCL prompted the apoptosis of A549 and NCI-H1299. Western blotting showed that knockdown of NCL decreased the phosphorylation of AKT and PI3K, which identified the downstream pathway of NCL. CONCLUSIONS: COL3A1-positive ECs have important effects on the development of LUAD and the formation of an immune microenvironment. Furthermore, we identified a key target gene, NCL, which is involved in the interaction between endothelial cells and cancer cells. NCL also affected the apoptosis and proliferation in LUAD through the PI3K-AKT pathway.

Is laparoscope surgery feasible for upper gastrointestinal cancer patients with a history of abdominal surgery?

Objective: To investigate the feasibility of laparoscopic abdominal mobilization in patients with cancers of the esophagus or gastroesophageal junction who have a history of abdominal surgery. Methods: A total of 132 patients who underwent resection for cancers of the esophagus or gastroesophageal junction from August 2018 to March 2022 in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, were selected (66 patients with a history of abdominal surgery (observation group) and 66 patients without a history of abdominal surgery (control group)). All patients were treated with preoperative neoadjuvant therapy, based on the clinical stage. Thoracoscopic and laparoscopic resection was performed under general anesthesia. The intraoperative and postoperative conditions and surgical complications were compared between the two groups. Results: No significant differences were found in baseline data between the observation group and the control group (p > 0.05). Laparoscopic abdominal mobilization was completed in both groups, and there were no significant differences between the two groups in the total operation time [(272.50 ± 86.45) min vs. (257.55 ± 67.96) min], abdominal mobilization time [(25.03 ± 9.82) min vs. (22.53 ± 3.88) min], blood loss [(119.09 ± 72.17) ml vs. (104.39 ± 43.82) ml], and postoperative time to first flatus [(3.44 ± 0.73) d vs. (3.29 ± 0.60) d] (p > 0.05). The abdominal mobilization time was longer in observation group than that in control group (p = 0.057). After excluding the patients (31/66) with a history of simple appendectomy from the observation group, the abdominal mobilization time was significantly longer in observation group than that in control group [(27.97 ± 12.16) min vs. (22.53 ± 3.88) min] (p < 0.05). There were significantly fewer dissected abdominal lymph nodes in the observation group than in the control group [(18.44 ± 10.87) vs. (23.09 ± 10.95), p < 0.05]. After excluding the patients (15/66) with a history of abdominal tumor surgery from the observation group, there was no significant difference in the number of dissected abdominal lymph nodes between the two groups [(20.62 ± 10.81) vs. (23.09 ± 10.95)] (p > 0.05).In addition, no postoperative complications, such as intestinal obstruction, abdominal infection and bleeding, occurred in either group. Conclusion: Patients with cancers of the esophagus or gastroesophageal junction who have a history of abdominal surgery are suitable for minimally invasive laparoscopic mobilization.

Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization.

Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection. We apply this method to plasma samples of 497 healthy controls and 780 patients of seven cancer types and develop an ensemble classifier by incorporating methylation, fragmentation, and CNA features. In the test cohort, our approach achieves an area under the curve value of 0.966 for overall cancer detection. Detection sensitivity for early-stage patients achieves 73% at 99% specificity. Finally, we demonstrate the feasibility to accurately localize the origin of cancer signals with combined methylation and fragmentation profiling of tissue-specific accessible chromatin regions. Overall, this proof-of-concept study provides a technical platform to utilize multimodal cfDNA features for improved cancer detection.

Association between radiotherapy and risk of second primary malignancies in patients with resectable lung cancer: a population-based study.

BACKGROUND: The most common form of treatment for non-metastatic lung cancer is surgery-based combination therapy, which may also include adjuvant radiotherapy or chemotherapy. Second primary malignancies (SPMs) are uncommon but significant radiation side effects in patients with resectable lung cancer, and SPMs have not been adequately investigated. Our study aims to assess the correlations of radiotherapy with the development of SPMs in patients with resectable lung cancer. METHODS: We screened for any primary malignancy that occurred more than five years after the diagnosis of resectable lung cancer. Based on the large cohort of the Surveillance, Epidemiology and End Results database, radiotherapy-correlated risks were estimated using the Poisson regression analysis and the cumulative incidence of SPMs was calculated using Fine-Gray competing risk regression analysis. RESULTS: Among the 62,435 patients with non-metastatic lung cancer undergoing surgery, a total of 11,341 (18.16%) patients have received radiotherapy. Our findings indicated that radiotherapy was substantially related to a high risk of main second solid malignancies (RR = 1.21; 95%CI, 1.08 to 1.35) and a negligible risk of main second hematologic malignancies (RR = 1.08; 95%CI, 0.84 to 1.37). With the greatest number of patients, the risk of acquiring a second primary gastrointestinal cancer was the highest overall (RR = 1.77; 95 percent CI, 1.44 to 2.15). The cumulative incidence and standardized incidence ratios of SPMs revealed similar findings. Furthermore, the young and the elderly may be more vulnerable, and the highest risk of acquiring most SPMs was seen more than ten years after lung cancer diagnosis. Additionally, more attention should be paid to the second primary gastrointestinal cancer in young individuals with resectable lung cancer. CONCLUSION: After receiving radiotherapy, an increased risk of developing second primary solid and gastrointestinal cancers was observed for patients with resectable lung cancer. The prevention of SPMs associated with radiotherapy requires further attention.

Global burden and temporal trends in incidence and mortality of oesophageal cancer.

INTRODUCTION: Oesophageal cancer is a prevalent and deadly cancer around the world. OBJECTIVES: We aimed to present a comprehensive analysis of the global geographic patterns and temporal trends in the mortality and incidence of oesophageal cancer. METHODS: The mortality and incidence data of oesophageal cancer in 2020 were obtained from the GLOBOCAN database. Based on World Health Organization (WHO) mortality database and the Cancer Incidence in Five Continents (CI5), we also retrieved the mortality and incidence age-standardized rates (ASRs) of oesophageal cancer. The average annual percentage changes (AAPCs) of mortality and incidence were calculated using the joinpoint regression analysis. RESULTS: Globally, 0.54 million deaths and 0.6 million new cases were identified in 2020. In the majority of countries of South America and Asia, the mortality and incidence trends have substantially decreased, but trends in European countries have varied. The prevalence in European nations varied, but the incidence in most other continents decreased dramatically. In terms of mortality, the global average rate was 5.6 per 100000, ranging from 16.7 (Malawi) to 0.28 (Belize). European countries varied in mortality, such as Norway (AAPC, male: 0.68; female: 0.89) and Ireland (AAPC, male: -0.96; female: -1.52). Most non-European countries saw large decreases in mortality, such as Singapore (AAPC, male: -4.78; female: -6.89). The elderly had more noticeable trends in mortality and incidence in most countries. CONCLUSIONS: We have identified different trends in mortality and incidence among European countries, whereas declining trends were identified in most non-European countries. However, increasing trends were identified in specific subgroups of some countries, such as men in Thailand. For populations with rising mortality and incidence trends, more preventative efforts are required.

A new N descriptor for non-small cell lung cancer: the classification based on anatomic location, number and ratio of metastatic lymph nodes.

Background: The current N classification, which is determined by the anatomical location of positive lymph nodes, does not effectively stratify N1 and N2 non-small cell lung cancer (NSCLC) patients into prognostically significant subgroups. Methods: We acquired the clinical data of 3,234 N1 and N2 NSCLC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). We eliminated patients undergoing chemotherapy or radiation because chemotherapy and radiotherapy might lower lymph node stage, and the SEER database does not distinguish between therapy administered before and after surgery. We developed the N-new classification based on the former N stage, the number and ratio of lymph nodes. Patients were finally classified into four categories (N1a, N1b, N2a, N2b). Then, the N-new classification was validated in subgroups based on a variety of clinical characteristics, such as tumor size. The multivariable Cox regression analysis, the decision curve analysis (DCA) and the time-dependent receiver operating characteristic (ROC) analysis were conducted to compare the performance of the N-new classification and the current N classification. Results: The cancer-specific survival (CSS) and overall survival were significantly different among each pair of N-new classification. And the same results were shown in the majority of the subgroups determined by various clinical characteristics. Compared with the current N classification (C-index, 0.639), the N-new classification (C-index, 0.652) performed better in classifying N1 and N2 NSCLC patients into subgroups with distinctive clinical outcomes. The 5-year CSS rates were 49.7%, 41.4%, 30.4% and 20.4% for N1a, N1b, N2a and N2b, respectively. Conclusions: When compared to the current N classification, the N-new classification could be a more reliable and accurate prognostic determinant, which is worth considering in the revision of the 9th edition of the tumor, node, metastasis (TNM) staging system.

RNA modification writer expression profiles predict clinical outcomes and guide neoadjuvant immunotherapy in non-small cell lung cancer.

BACKGROUND: RNA modifications, including adenosine-to-inosine RNA editing, alternative polyadenylation, m1A and m6A, play a significant role in tumorigenesis and tumor immunity. However, the functions of RNA modification enzymes (writers) in immunotherapy and tumor microenvironment (TME) remain unknown. METHODS: Nonnegative matrix factorization clustering was applied to identify RNA modification clusters in lung adenocarcinoma, one of the most prevalent subtypes of non-small cell lung cancer (NSCLC). CIBERSORT and ESTIMATE algorithms were performed to depict TME characteristics. Additionally, a scoring system called Writer-Score was established to quantify RNA modification patterns and subsequently predict clinical outcomes. We subsequently used RNA sequencing, targeted DNA sequencing and multiplex immunofluorescence to further evaluate the efficacy of Writer-Score in NSCLC patients receiving neoadjuvant immunotherapy. FINDINGS: We identified three distinct RNA modification clusters and two DEGclusters, which were shown to be strongly associated with a variety of TME features and biological processes. Additionally, the Writer-Score served as an important factor in post-transcriptional events and immunotherapy. The Writer-Score was capable of properly predicting the prognosis of NSCLC patients receiving neoadjuvant PD-1 inhibitor therapy. INTERPRETATION: Our work systematically analyzed four types of RNA modifications and constructed a scoring system to guide neoadjuvant immunotherapy in NSCLC, which highlighted the writers' roles in post-transcriptional events, TME and neoadjuvant immunotherapy. FUNDING: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Identifying novel tumor-related antigens and immune phenotypes for developing mRNA vaccines in lung adenocarcinoma.

The mRNA vaccines have been a novel strategy of immunotherapies for multiple cancers. Although several types of mRNA vaccines have been investigated and validated in some studies, their efficacy among patients with lung adenocarcinoma (LUAD) remains largely unknown. The number of tumor-associated antigens is not enough and no study focuses on stratifying the subgroup of LUAD patients suitable for vaccination. Based on the expression profiles of immune-related genes, consensus clustering was performed to identify the most appropriate phenotype for vaccination. The immune landscape of LUAD was shown via the graph learning-based dimensionality reduction analysis. We screened for five mutated and upregulated LUAD-related antigens (CCNB1, KIAA0101, PBK, OIP5 and PLEK2) that were highly correlated with immune infiltrating cells and unfavorable clinical outcomes. And three distinct immune phenotypes were identified in the TCGA and GSE72094 cohorts. Group S1 was an immunological "hot" cluster and related to a better prognosis, whereas Group S2&S3 was an immunological "cold" cluster and associated with a poorer prognosis. At last, the results revealed heterogeneity of LUAD patients in the immune landscape. We identified five potential cancer-related antigens for mRNA vaccines, and Group S2&S3 were the most suitable phenotypes for vaccination.

Worldwide burden and epidemiological trends of tracheal, bronchus, and lung cancer: A population-based study.

BACKGROUND: We comprehensively analyzed the global burdens and trends in incidence and mortality of tracheal, bronchus, and lung (TBL) cancer among subgroups of distinctive ages and genders. METHODS: We retrieved incidence and mortality rates of lung cancer in 2020 from the GLOBOCAN database among 185 countries. The incidence and mortality age-standardized rates (ASRs) were mostly obtained from Cancer Incidence in Five Continents and World Health Organization mortality database, respectively. The joinpoint regression analysis has been conducted to evaluate the average annual percentage change of incidence and mortality in recent years. FINDINGS: Trends in the incidence and mortality were decreasing among men in most countries, whereas the trends were increasing among women in some regions. As for mortality, most countries had a decreasing trend in mortality among males, but increasing trends were observed in more than half of countries among females. Furthermore, the majority of countries showed a significant decrease in incidence among males (AAPCs, -0·34 to -6·53), whereas most countries had a significant increase among females (AAPCs, 9·39 to 0·6), especially in European countries. In addition, a more drastic decrease was identified in the trends of the incidence among young people. 33 countries had a drastic decrease among males, especially in countries in Europe (AAPCs, -0·93 to -11·71). And 15 countries showed a significant decrease in incidence among young women (AAPCs, -0·94 to -9·35). INTERPRETATION: Decreasing incidence and mortality trends were identified in TBL cancer, particularly among all-age men and women younger than 50 years old. But some other groups of individuals showed an opposite trend, such as women in European countries. More preventive interventions are required for the specific populations. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Research Progress of Anti-PD-1/PD-L1 Immunotherapy Related Mechanisms and Predictive Biomarkers in NSCLC.

Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) is an important pair of immune checkpoints (IC), which play an essential role in the immune escaping process of tumors. Anti-PD-1/PD-L1 immunotherapy can block the suppression effect of the immune system produced by tumor cells through the PD-1/PD-L1 axis and restore the pernicious effect of the immune system on tumor cells. The specific mechanism of anti-PD-1/PD-L1 immunotherapy is closely related to PI3K (phosphatidylinositol 3-kinase)/AKT (AKT serine/threonine kinase 1), JNK (c-Jun N-terminal kinase), NF-kB (nuclear factor-kappa B subunit 1), and other complex signaling pathways. Patients receiving anti-PD-1/PD-L1 immunotherapy are prone to drug resistance. The mechanisms of drug resistance mainly include weakening recognition of tumor antigens by immune cells, inhibiting activation of immune cells, and promoting the production of suppressive immune cells and molecules. Anti-PD-1/PD-L1 immunotherapy plays a vital role in non-small cell lung cancer (NSCLC). It is essential to find better efficacy prediction-related biomarkers and screen patients suitable for immunotherapy. At present, common biomarkers related to predicting immune efficacy mainly include PD-L1 expression level in tumors, tumor mutation burden (TMB), microsatellite instability (MSI)/mismatch repair (MMR), mutations of driver gene, etc. However, the screening efficacy of each indicator is not ideal, and the combined application of multiple indicators is currently used. This article comprehensively reviews anti-PD-1/PD-L1 immunotherapy-related mechanisms, drug resistance-related mechanisms, and therapeutic efficacy-related predictive biomarkers.

Comprehensive analysis of PD-L1 expression, tumor-infiltrating lymphocytes, and tumor microenvironment in LUAD: differences between Asians and Caucasians.

BACKGROUNDS: The characteristics of programmed cell death protein-1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) patients are closely related to immunotherapy, and there are differences between Asians and Caucasians. METHODS: Acquire the transcriptome data of the Cancer Genome Atlas and Chinese LUAD patients. R software was used to analyze the differential expression of genes, prognosis, and gene function. Use CIBERSORT for TIL-related analysis and ESTIMATE for TME-related analysis. RESULTS: The expression of PD-L1 in tumor tissues of Caucasian LUAD patients was lower than that in normal tissues, while there was no significant difference in Asians. There was no statistical difference between PD-L1 expression and prognosis. The composition of TILs between Caucasian and Asian LUAD patients was quite different. There was no correlation between TILs and prognosis in Caucasians. However, the higher content of resting mast cells indicated a better prognosis in Asians. The Caucasian patients with higher immune and estimate scores had a better prognosis (p = 0.021, p = 0.025). However, the Asian patients with a higher estimate score had a worse prognosis (p = 0.024). The high expression of COL5A2 (p = 0.046, p = 0.027) and NOX4 (p = 0.020, p = 0.019) were both associated with the poor prognosis in Caucasians and Asians. CONCLUSION: There are many differences in the characteristics of PD-L1 expression, TILs, and TME between Caucasian and Asian LUAD patients. This provides a certain hint for the selection of specific immunotherapy strategies separately for Caucasian and Asian LUAD patients.

Clinicopathological characteristics and prognostic factors of primary pulmonary lymphoma.

BACKGROUND: Primary pulmonary lymphoma (PPL) is a rare extranodal lymphoma originating from the lung, accounting for 0.5-1.0% of primary lung malignant tumors. Previous case reports or cohort studies included a limited sample size; therefore, the understanding of the disease remains inadequate, and clinical data regarding PPL are limited. METHODS: Patients with PPL diagnosed histologically and radiologically between January 2000 and December 2019 at our center were retrospectively analyzed. RESULTS: In total, 90 consecutive cases were included in this research. Forty-seven (52.2%) patients were female, and the median age was 54 years old. Non-Hodgkin's lymphoma (PPNHL) was the most common type of PPL (71/90, 78.9%), and mucosa-associated lymphoid tissue (MALT) lymphoma was the most common pathological subtype of PPNHL (56.3%) followed by diffuse large B-cell lymphoma (DLBCL) (32.4%). Thirty-nine (43.3%) patients underwent surgical treatment, and the others received chemotherapy alone or combined with radiotherapy. The estimated 5-year overall survival (OS) rates of MALT lymphoma and non-MALT lymphoma were 68.9% and 65.9%, respectively. Univariate analysis of PPL showed that clinicopathological features that significantly correlated with worse OS were age over 60 years (P=0.006<0.05), elevated LDH (P=0.029<0.05) and ß2-MG (P=0.048<0.05) levels, clinical stage II2E and greater (P=0.015<0.05), and nonsurgical treatment (P=0.046<0.05). Age (P=0.013<0.05) was an independent prognostic factor for the 5-year OS of patients through multivariate analysis. CONCLUSIONS: Age over 60 years old, elevated LDH and ß2-MG levels, clinical stage II2E disease or higher, and nonsurgical treatment were associated with poor prognosis in patients with PPL. Age can be used as a potential independent prognostic factor for PPL.

Urban heat island effects of various urban morphologies under regional climate conditions.

Previous studies of the effects of regional climate conditions on urban heat islands (UHIs) focused mostly on surface UHIs, whereas few considered canopy layer UHIs. In the present study, a numerical modeling method is used to investigate the impacts of regional climate conditions on canopy layer UHIs at the district scale while controlling for the urban morphology. The urban morphology is classified according to the local climate zone (LCZ) system as LCZ1-LCZ6. Analysis of the spatial distribution of the urban heat island intensity (UHII) show that the nighttime and daytime UHII are most significantly correlated with the air temperature and wind speed, respectively. In five typical cities, LCZ1 has the most obvious urban heat island (UHI) effect, with an average annual UHII of 1-2.3 °C, which is about 1.5 times that for LCZ4. Reducing the building density has more significant influence on mitigating the UHI effect, where reducing the building height and building density reduce the heat island degree-hours (HIdh) by about 20% and 30%, respectively. The relationships between the UHII and meteorological conditions vary among different periods. For example, the correlation between UHII and average wind speed is more significant in the winter and at night. Our results help to understand the relationships between regional climate conditions and the canopy layer UHI at the district scale.

Primary pulmonary epithelioid malignant peripheral nerve sheath tumor in a child: a case report.

Primary pulmonary malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas originating from intrapulmonary nerve sheath and have been rarely observed in children. Here, we report a case of a 16-year-old child who presented with a mass located in the upper lobe of right lung. The patient underwent a sleeve lobectomy and the pathological diagnosis of the tumor was primary pulmonary epithelioid MPNST. Despite the radical resection, multiple suspected metastasis occurred in heart, lung and muscles less than 2 years after the operation and the patient died 6 months after the metastasis.

Clinicopathological parameters predicting recurrence of pT1N0 esophageal squamous cell carcinoma.

AIM: To identify the clinicopathological characteristics of pT1N0 esophageal squamous cell carcinoma (ESCC) that are associated with tumor recurrence. METHODS: We reviewed 216 pT1N0 thoracic ESCC cases who underwent esophagectomy and thoracoabdominal two-field lymphadenectomy without preoperative chemoradiotherapy. After excluding those cases with clinical follow-up recorded fewer than 3 mo and those who died within 3 mo of surgery, we included 199 cases in the current analysis. Overall survival and recurrence-free survival were assessed by the Kaplan-Meier method, and clinicopathological characteristics associated with any recurrence or distant recurrence were evaluated using univariate and multivariate Cox proportional hazards models. Early recurrence (≤ 24 mo) and correlated parameters were assessed using univariate and multivariate logistic regression models. RESULTS: Forty-seven (24%) patients had a recurrence at 3 to 178 (median, 33) mo. The 5-year recurrence-free survival rate was 80.7%. None of 13 asymptomatic cases had a recurrence. Preoperative clinical symptoms, upper thoracic location, ulcerative or intraluminal mass macroscopic tumor type, tumor invasion depth level, basaloid histology, angiolymphatic invasion, tumor thickness, submucosal invasion thickness, diameter of the largest single tongue of invasion, and complete negative aberrant p53 expression were significantly related to tumor recurrence and/or recurrence-free survival. Upper thoracic tumor location, angiolymphatic invasion, and submucosal invasion thickness were independent predictors of tumor recurrence (Hazard ratios = 3.26, 3.42, and 2.06, P < 0.001, P < 0.001, and P = 0.002, respectively), and a nomogram for predicting recurrence-free survival with these three predictors was constructed. Upper thoracic tumor location and angiolymphatic invasion were independent predictors of distant recurrence. Upper thoracic tumor location, angiolymphatic invasion, submucosal invasion thickness, and diameter of the largest single tongue of invasion were independent predictors of early recurrence. CONCLUSION: These results should be useful for designing optimal individual follow-up and therapy for patients with T1N0 ESCC.

[Pattern of lymphatic metastasis and risk factor of esophageal carcinoma that invades less than adventitia].

OBJECTIVE: To explore the pattern of lymphatic metastasis and risk factors of esophageal carcinoma that invades less than adventitia. METHODS: Clinical data of 484 patients receiving esophagectomy from January 2011 to August 2014 were reviewed, whose carcinoma invaded less than adventitia. The lymph node metastasis pattern of the primary tumor and corresponding influence factor were analyzed. RESULTS: Total lymph node metastatic rate was 32.0% (155/484). Sixteen of 61 upper thoracic esophageal carcinoma patients (26.2%) had lymphatic metastasis. Fifty-five of 201 middle thoracic esophageal carcinoma patients (27.4%) had lymphatic metastasis. Eighty-four of 222 lower thoracic esophageal carcinoma patients(37.8%) had lymphatic metastasis. The deeper tumor invaded, the easier lymph node metastasis occurred, as well as the lower of the tumor differentiation and the larger of the tumor diameter. Multivariate analysis revealed lesion diameter (P=0.005), differentiation degree (P=0.007) and invasion depth (P=0.001) were independent risk factors of lymphatic metastasis in esophageal cancer that invaded less than adventitia. CONCLUSION: Depth of tumor invasion, diameter of tumor and tumor differentiation are risk factors of lymph node metastasis of esophageal carcinoma that invades less than adventitia.