Asiaticoside Inhibits Growth and Metastasis in Non-Small Cell Lung Cancer by Disrupting EMT via Wnt/ß-Catenin Pathway.

Non-small cell lung cancer (NSCLC) is the primary inducer of cancer-related death worldwide. Asiaticoside (ATS) is a triterpenoid saponin that has been indicated to possess an antitumor activity in several malignancies. Nonetheless, its detailed functions in NSCLC remain unclarified. In this study, NSCLC cells were exposed to various doses of ATS. Functional experiments were employed to estimate the ATS effect on NSCLC cell behaviors. Western blotting was implemented for protein expression evaluation. A xenograft mouse model was established to assess the ATS effect on NSCLC in vivo. The results showed that ATS restrained NSCLC cell proliferation, cell cycle progression, migration, and invasiveness. ATS reversed TGF-ß-induced promotion in epithelial-mesenchymal transition (EMT). Mechanistically, ATS inhibited Wnt/ß-catenin signaling in NSCLC. Upregulating ß-catenin restored ATS-mediated suppression of NSCLC cell aggressiveness. Moreover, ATS administration repressed tumorigenesis in tumor-bearing mice. In conclusion, ATS represses growth and metastasis in NSCLC by blocking EMT via the inhibition of Wnt/ß-catenin signaling.

The genomes of two parasitic wasps that parasitize the diamondback moth.

BACKGROUND: Parasitic insects are well-known biological control agents for arthropod pests worldwide. They are capable of regulating their host's physiology, development and behaviour. However, many of the molecular mechanisms involved in host-parasitoid interaction remain unknown. RESULTS: We sequenced the genomes of two parasitic wasps (Cotesia vestalis, and Diadromus collaris) that parasitize the diamondback moth Plutella xylostella using Illumina and Pacbio sequencing platforms. Genome assembly using SOAPdenovo produced a 178 Mb draft genome for C. vestalis and a 399 Mb draft genome for D. collaris. A total set that contained 11,278 and 15,328 protein-coding genes for C. vestalis and D. collaris, respectively, were predicted using evidence (homology-based and transcriptome-based) and de novo prediction methodology. Phylogenetic analysis showed that the braconid C. vestalis and the ichneumonid D. collaris diverged approximately 124 million years ago. These two wasps exhibit gene gains and losses that in some cases reflect their shared life history as parasitic wasps and in other cases are unique to particular species. Gene families with functions in development, nutrient acquisition from hosts, and metabolism have expanded in each wasp species, while genes required for biosynthesis of some amino acids and steroids have been lost, since these nutrients can be directly obtained from the host. Both wasp species encode a relative higher number of neprilysins (NEPs) thus far reported in arthropod genomes while several genes encoding immune-related proteins and detoxification enzymes were lost in both wasp genomes. CONCLUSIONS: We present the annotated genome sequence of two parasitic wasps C. vestalis and D. collaris, which parasitize a common host, the diamondback moth, P. xylostella. These data will provide a fundamental source for studying the mechanism of host control and will be used in parasitoid comparative genomics to study the origin and diversification of the parasitic lifestyle.

Predicting pathological grade of stage I pulmonary adenocarcinoma: a CT radiomics approach.

Objectives: To investigate the value of CT radiomics combined with radiological features in predicting pathological grade of stage I invasive pulmonary adenocarcinoma (IPA) based on the International Association for the Study of Lung Cancer (IASLC) new grading system. Methods: The preoperative CT images and clinical information of 294 patients with stage I IPA were retrospectively analyzed (159 training set; 69 validation set; 66 test set). Referring to the IASLC new grading system, patients were divided into a low/intermediate-grade group and a high-grade group. Radiomic features were selected by using the least absolute shrinkage and selection operator (LASSO), the logistic regression (LR) classifier was used to establish radiomics model (RM), clinical-radiological features model (CRM) and combined rad-score with radiological features model (CRRM), and visualized CRRM by nomogram. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the performance and fitness of models. Results: In the training set, RM, CRM, and CRRM achieved AUCs of 0.825 [95% CI (0.735-0.916)], 0.849 [95% CI (0.772-0.925)], and 0.888 [95% CI (0.819-0.957)], respectively. For the validation set, the AUCs were 0.879 [95% CI (0.734-1.000)], 0.888 [95% CI (0.794-0.982)], and 0.922 [95% CI (0.835-1.000)], and for the test set, the AUCs were 0.814 [95% CI (0.674-0.954)], 0.849 [95% CI (0.750-0.948)], and 0.860 [95% CI (0.755-0.964)] for RM, CRM, and CRRM, respectively. Conclusion: All three models performed well in predicting pathological grade, especially the combined model, showing CT radiomics combined with radiological features had the potential to distinguish the pathological grade of early-stage IPA.

Germinal center B-cell subgroups in the tumor microenvironment cannot be overlooked: Their involvement in prognosis, immunotherapy response, and treatment resistance in head and neck squamous carcinoma.

Background: More than 60 % of patients with head and neck squamous carcinoma (HNSCC) are diagnosed at advanced stages and miss radical treatment. This has prompted the need to find new biomarkers to achieve early diagnosis and predict early recurrence and metastasis of tumors. Methods: Single-cell RNA sequencing (scRNA-seq) data from HNSCC tissues and peripheral blood samples were obtained through the Gene Expression Omnibus (GEO) database (GSE164690) to characterize the B-cell subgroups, differentiation trajectories, and intercellular communication networks in HNSCC and to construct a prognostic model of the associated risks. In addition, this study analyzed the differences in clinical features, immune cell infiltration, functional enrichment, tumor mutational burden (TMB), and drug sensitivity between the high- and low-risk groups. Results: Using scRNA-seq of HNSCC, we classified B and plasma cells into a total of four subgroups: naive B cells (NBs), germinal center B cells (GCBs), memory B cells (MBs), and plasma cells (PCs). Pseudotemporal trajectory analysis revealed that NBs and GCBs were at the early stage of B cell differentiation, while MBs and PCs were at the end. Cellular communication revealed that GCBs acted on tumor cells through the CD99 and SEMA4 signaling pathways. The independent prognostic value, immune cell infiltration, TMB and drug sensitivity assays were validated for the MEF2B+ GCB score groups. Conclusions: We identified GCBs as B cell-specific prognostic biomarkers for the first time. The MEF2B+ GCB score fills the research gap in the genetic prognostic prediction model of HNSCC and is expected to provide a theoretical basis for finding new therapeutic targets for HNSCC.

Construction of a prognostic model of luteolin for endometrial carcinoma.

OBJECTIVE: Endometrial cancer is one of the most common tumors of the female reproductive system, and the existing treatment options for advanced and metastatic endometrial cancer have certain limitations. The antitumor activity of luteolin has been gradually discovered. The purpose of this study was to predict the potential of luteolin in the treatment of endometrial cancer and to provide reference for future clinical drug use. METHODS: The target gene database of luteolin and differential gene dataset of uterine corpus endometrial carcinoma (UCEC) have been constructed to obtain the differential genes (DR-DEGs) for luteolin and UCEC. The Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis are performed at the same time. Genes associated with prognosis in DR-DEGs were screened and validated using univariate and multivariate COX risk regression analysis so as to construct a prognostic model. Genes are divided into high-risk and low-risk groups according to risk scores for survival analysis and the predictive effect of the model is evaluated. The role of immune function in UCEC is investigated by immune infiltration and immune checkpoint analysis Finally, Transwell experiment was conducted to investigate the effect of luteolin on the migration ability of endometrial cancer cells, and the expression changes of MMP1, IL-17 and VEGF were detected by q-PCR. RESULTS: Through the GO, KEGG and GSEA enrichment analysis, we have found a significant enrichment in "IL 17 signaling (IL-17) pathway", "oxidative stress response" and "HOMOLOGOUS_RECOMBINATION". Through multivariate COX risk regression analysis, four genes associated with the prognosis are harvested, including "PRSS1, MMP1, ERBB2 and NUF2" which belong to high-risk genes. Kaplan-Meier analysis shows that the survival rate in the high risk group is lower than that in the low risk group, and the receiver operating characteristic (ROC) curve reveals that the predictive effect of the model is good and stable (area under 1-year curve (AUC) 0.569, two-year AUC 0.628 and three-year AUC 0.653). Immune infiltration and immune checkpoint analysis suggest that "CD40", "T cells regulatory (Tregs)", "dendritic cells resting" and "dendritic cells activated" are correlated with survival and prognosis in UCEC patients. In in vitro experiments, we found that the migration ability of endometrial cancer cells was significantly reduced after luteolin treatment, and the expressions of MMP1, IL-17 and VEGF were all decreased. CONCLUSION: Through bioinformatic analysis, we found that luteolin could slow down the progression of UCEC by inhibiting the production of inflammatory mediators such as IL-17 and oxidative stress, and constructed genetic prognostic models associated with them: PRSS1, MMP1, ERBB2 and NUF2, respectively. In addition, we found that luteolin has an inhibitory effect on the migration of endometrial cancer cells and can reduce the expressions of MMP1, IL-17 and VEGF, thus easing the progression of endometrial cancer.

Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis.

N-7 methylguanine (m7G) is one of the most common RNA base modifications in post-transcriptional regulation, which participates in multiple processes such as transcription, mRNA splicing and translation during the mRNA life cycle. However, its expression and prognostic value in uterine corpus endometrial carcinoma (UCEC) have not been systematically studied. In this paper, the data such as gene expression profiles, clinical data of UCEC patients, somatic mutations and copy number variants (CNVs) are obtained from the cancer genome atlas (TCGA) and UCSC Xena. By analyzing the expression differences of m7G-related mRNA in UCEC and plotting the correlation network maps, a risk score model composed of four m7G-related mRNAs (NSUN2, NUDT3, LARP1 and NCBP3) is constructed using least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression in order to identify prognosis and immune response. The correlation of clinical prognosis is analyzed between the m7G-related mRNA and UCEC via Kaplan-Meier method, receiver operating characteristic (ROC) curve, principal component analysis (PCA), t-SNE, decision curve analysis (DCA) curve and nomogram etc. It is concluded that the high risk is significantly correlated with (P < 0.001) the poorer overall survival (OS) in patients with UCEC. It is one of the independent risk factors affecting the OS. Differentially expressed genes are identified by R software in the high and low risk groups. The functional analysis and pathway enrichment analysis have been performed. Single sample gene set enrichment analysis (ssGSEA), immune checkpoints, m6A-related genes, tumor mutation burden (TMB), stem cell correlation, tumor immune dysfunction and rejection (TIDE) scores and drug sensitivity are also used to study the risk model. In addition, we have obtained 3 genotypes based on consensus clustering, which are significantly related to (P < 0.001) the OS and progression-free survival (PFS). The deconvolution algorithm (CIBERSORT) is applied to calculate the proportion of 22 tumor infiltrating immune cells (TIC) in UCEC patients and the estimation algorithm (ESTIMATE) is applied to work out the number of immune and matrix components. In summary, m7G-related mRNA may become a potential biomarker for UCEC prognosis, which may promote UCEC occurrence and development by regulating cell cycles and immune cell infiltration. It is expected to become a potential therapeutic target of UECE.

A multi-omics-based investigation of the prognostic and immunological impact of necroptosis-related mRNA in patients with cervical squamous carcinoma and adenocarcinoma.

Necroptosis is a kind of programmed necrosis mode that plays a double-edged role in tumor progression. However, the role of necroptosis-related Messenger RNA (mRNA) in predicting the prognosis and immune response of cervical squamous carcinoma and adenocarcinoma (CESC) has not been fully studied. Firstly, the incidence of somatic mutation rate and copy number variation for 74 necroptosis-related mRNAs (NRmRNAs) were analyzed. Secondly, CESC patients were divided into four stable clusters based on the consensus clustering results and analyzed for correlations with a series of clinical factors. Subsequently, a total of 291 The Cancer Genome Atlas samples were randomly divided into either training or validation cohorts. A Cox proportional hazard model consisting of three NRmRNAs (CXCL8, CLEC9A, and TAB2) was constructed by univariate, least absolute shrinkage and selection operator and multivariate COX regression analysis to identify the prognosis and immune response. Its performance and stability were further validated in another testing dataset (GSE44001) from Gene Expression Omnibus database. The results of the receiver operating characteristic curve, principal component analysis, t-SNE, and nomogram indicated that the prognostic model we constructed can serve as an independent prognostic factor. The combination of the prognostic model and the classic TNM staging system could improve the performance in predicting the survival of CESC patients. In addition, differentially expressed genes from high and low-risk patients are screened by R software for functional analysis and pathway enrichment analysis. Besides, single-sample gene set enrichment analysis revealed that tumor-killing immune cells were reduced in the high-risk group. Moreover, patients in the low-risk group are more likely to benefit from immune checkpoint inhibitors. The analysis of tumor immune dysfunction and exclusion scores, M6A-related genes, stem cell correlation and Tumor mutational burden data with clinical information has quantified the expression levels of NRmRNAs between the two risk subgroups. According to tumor immune microenvironment scores, Spearman's correlation analysis, and drug sensitivity, immunotherapy may have a higher response rate and better efficacy in patients of the low-risk subgroup. In conclusion, we have reported the clinical significance of NRmRNAs for the prognosis and immune response in CESC patients for the first time. Screening of accurate and effective prognostic markers is important for designing a multi-combined targeted therapeutic strategy and the development of individualized precision medicine.

Necroptosis-related lncRNA signature predicts prognosis and immune response for cervical squamous cell carcinoma and endocervical adenocarcinomas.

Necroptosis, a programmed form of necrotic cell death, plays critical regulatory roles in the progression and metastatic spread of cancers such as cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, there are few articles systematically analyzing the necroptosis-related long non-coding RNAs (NRlncRNAs) correlated with CESC patients. Both RNA-sequencing and clinical data of CESC patients are downloaded from TCGA database in this study. Pearson correlation analysis, least absolute shrinkage, operator algorithm selection and Cox regression model are employed to screen and create a risk score model of eleven-NRlncRNAs (MIR100HG, LINC00996, SNHG30, LINC02688, HCG15, TUBA3FP, MIAT, DBH-AS1, ERICH6-AS1SCAT1, LINC01702) prognostic. Thereafter, a series of tests are carried out in sequence to evaluate the model for independent prognostic value. Gene set enrichment analytic paper, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analytic paper make it clear that immune-related signaling pathways are very rich in the high-risk subgroup. Additionally, the prognostic risk score model is correlated to immune cell infiltration, potential immune checkpoint, immune function, immune micro-environmental and m6A-related gene. Mutation frequency in mutated genes and survival probability trend are higher in the low-risk subgroup in most of test cases when compared to the high-risk subgroup. This study constructs a renewed prognostic model of eleven-NRlncRNAs, which may make some contribution to accurately predicting the prognosis and the immune response from CESC patients, and improve the recognition of CESC patients and optimize customized treatment regimens to some extent.

Beware of Pleural Thickening and Calcification: An Enlightenment from a Case of Tuberculous Pleurisy.

Tuberculous pleurisy, a type of extra-pulmonary tuberculosis, is the pleural inflammation caused by hypersensitive response of the pleural cavity stimulated by mycobacterium tuberculosis and its metabolites. If the patient does not receive timely and effective treatment and intervention, a large amount of fibrin will be deposited which will cause pleural thickening, adhesions, and even calcification. At present, clinical cases of typical pleural thickening and calcification have been rarely reported. In this paper, we will report a case of significant pleural thickening and calcification caused by tuberculous pleurisy; moreover, the patient earliest got tuberculous pleurisy about in 20 years ago and had received anti-tuberculous treatment at that time. The patient's typical crescent-shaped shadow created by pleural thickening and calcification is very rare in the domestic and international literature.

A Rare Giant Midesophageal Diverticulum: Fever is the Only Symptom.

A 55-year-old man was treated at the village hospital with six months medical history of recurrent chills and fever. Due to the lack of imaging examination, antipyretic and anti-infective medications were given. Although symptomatic treatment can relieve fever symptoms, symptoms easily flare up again two to three days after taking the drug. Later, the patient suffered from fever again during the COVID-19 epidemic and was sent to our hospital for isolation and treatment. During this hospitalization, chest CT examination is mandatory for all patients in order to meet the requirements of epidemic prevention and control. This led to the inadvertent discovery of a large cystic solid mass in the right thoracic cavity communicating with the esophageal lumen. The patient was preliminarily diagnosed as giant midesophageal diverticulum after three-dimensional CT image reconstruction of the chest was reviewed. Considering the patient's persistent fever with poor nutritional status, we decided to temporarily place two gastric tubes (diverticulum decompression and gastrointestinal nutrition), and antibiotics were used at the same time as another main treatment. However, after the symptoms eased and nutritional status improved, he refused all further treatment. We believe that this patient's diverticulum is very classic, and the treatment plan is highly integrated with the needs of epidemic prevention and control and achieves a satisfactory therapeutic effect, so we hope to provide colleagues with new diagnosis and treatment enlightenment through this case.

The characteristics and evolution of pulmonary fibrosis in COVID-19 patients as assessed by AI-assisted chest HRCT.

The characteristics and evolution of pulmonary fibrosis in patients with coronavirus disease 2019 (COVID-19) have not been adequately studied. AI-assisted chest high-resolution computed tomography (HRCT) was used to investigate the proportion of COVID-19 patients with pulmonary fibrosis, the relationship between the degree of fibrosis and the clinical classification of COVID-19, the characteristics of and risk factors for pulmonary fibrosis, and the evolution of pulmonary fibrosis after discharge. The incidence of pulmonary fibrosis in patients with severe or critical COVID-19 was significantly higher than that in patients with moderate COVID-19. There were significant differences in the degree of pulmonary inflammation and the extent of the affected area among patients with mild, moderate and severe pulmonary fibrosis. The IL-6 level in the acute stage and albumin level were independent risk factors for pulmonary fibrosis. Ground-glass opacities, linear opacities, interlobular septal thickening, reticulation, honeycombing, bronchiectasis and the extent of the affected area were significantly improved 30, 60 and 90 days after discharge compared with at discharge. The more severe the clinical classification of COVID-19, the more severe the residual pulmonary fibrosis was; however, in most patients, pulmonary fibrosis was improved or even resolved within 90 days after discharge.

Factors affecting recurrent positive RT-PCR results in clinically cured COVID-19 patients: a multicenter study.

The aim of this study was to evaluate factors affecting the recurrence of positive RT-PCR results. By performing a retrospective analysis, we evaluated the clinical data of recurrent positive coronavirus disease 2019 (COVID-19) patients in multiple medical institutions in Wuhan. We recruited COVID-19 patients who were hospitalized from January 1 to March 10, 2020, in three tertiary hospitals in Wuhan, met the discharge criteria and received at least one additional nucleic acid test before leaving the hospital. According to the RT-PCR results, patients were split into a recurrent positive group (RPos group) and a nonrecurrent positive group (non-RPos group). Clinical characteristics, therapeutic schedules and antibody titers were compared between the two groups. AI-assisted chest high-resolution computed tomography (HRCT) technology was applied to investigate pulmonary inflammatory exudation and compare the extent of lung areas with different densities. This study involved 122 COVID-19 patients. There were no significant differences in age, sex, preexisting diseases, clinical symptoms, clinical classification, course of disease, therapeutic schedules or serum-specific antibodies between the two groups. A higher proportion of patients who showed pulmonary inflammatory exudation on HRCT scans were recurrent positive at the time of discharge than other patients (81.6% vs 13.7%, P < 0.01). In addition, the degree of pulmonary fibrosis was higher in the RPos group than in the non-RPos group (P < 0.05). Subpleural exudation at the peripheral edge of the lung and extensive pulmonary fibrosis at the time of discharge represent risk factors for the recurrence of COVID-19.

The diagnostic value of dynamic volume computed tomography angiography in children with anomalous origin of the left coronary artery from the pulmonary artery.

There have been almost no reports on the technique of dynamic volume computed tomography angiography (DVCTA) in children with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Twelve children with ALCAPA, aged 5 months to 15 years, were enrolled in this retrospective study to explore the clinical value of DVCTA in the diagnosis of ALCAPA in children. All patients underwent low-dose prospective ECG-gated 320-slice DVCTA and transthoracic echocardiography. Two radiologists evaluated the image quality of the DVCTA and recorded the radiation dose at the same time. The accuracy of DVCTA in the diagnosis of ALCAPA was 100%, with the left coronary artery (LCA) opening in the left wall of the pulmonary artery in 4 cases (33.3%), the right wall in 2 cases (16.7%), and the posterior wall in 6 cases (50.0%). All children completed 320-slice DVCTA at a single timepoint; all of the images were diagnosable, and the subjective score was 3.3±0.6, with good consistency between the evaluations performed by the two radiologists (k=0.79). From the echocardiographs of these cases, 4 cases (33.3%) of ALCAPA were diagnosed correctly, 4 cases (33.3%) were misdiagnosed as LCA-pulmonary artery fistula, and 4 cases (33.3%) were missed, including a small LCA that was not displayed in 2 cases. The average CT radiation dose was 0.83±0.57 mSv. Low-dose DVCTA clearly showed the origin, course, and collateral vessels of ALCAPA and could be used reliably for noninvasive diagnosis of ALCAPA in children.

Clinical characteristics and prognosis of COVID-19 patients with initial presentation of lung lesions confined to a single pulmonary lobe.

BACKGROUND: COVID-19 patients showed certain characteristic features of multiple signs in bilateral lungs. Some patients only had a single pulmonary lobe lesion, which has not been reported previously. Single pulmonary lobe lesions are easily missed or misdiagnosed if they do not receive enough attention. OBJECTIVE: To study the imaging manifestations, clinical features and outcomes of patients with COVID-19 with only one single pulmonary lobe lesion. METHODS: Patient clinical data were collected only from patients with confirmed SARS-CoV-2 infection by RT-PCR, which was confined to only single lobe lesions on chest CT imaging findings at the onset. Which lobe was frequently involved, the imaging manifestations, clinical features and outcomes were also analyzed. RESULT: From January 1, 2020, to March 14, 2020, a total of 367 inpatients were diagnosed with COVID-19, in which 50 (13.6%) patients were confirmed with only one single pulmonary lobe lesion. The most frequently involved lobe was the right lower lobe (18 patients, 36%, highest). Lesions in the lower lobe easily spread to all lobes of the bilateral lungs (P<0.001, χ2=10.264), especially the left lower lobe, and were less frequent in the right upper lobe. During hospitalization, 2 (4%) patients were admitted to the ICU, 2 (4%) patients died, and 28 (56%) patients developed lesions in other lobes within 6.32±3.71 days. CONCLUSIONS: The general pattern of COVID-19 imaging with localized nodules may also cause severe respiratory symptoms of bilateral lung disease, serious complications, or even death in patients with multiple lobe lesions or bilateral lung lesions, which should not be underestimated.

Parasitic insect-derived miRNAs modulate host development.

Parasitic wasps produce several factors including venom, polydnaviruses (PDVs) and specialized wasp cells named teratocytes that benefit the survival of offspring by altering the physiology of hosts. However, the underlying molecular mechanisms for the alterations remain unclear. Here we find that the teratocytes of Cotesia vestalis, an endoparasitoid of the diamondback moth Plutella xylostella, and its associated bracovirus (CvBV) can produce miRNAs and deliver the products into the host via different ways. Certain miRNAs in the parasitized host are mainly produced by teratocytes, while the expression level of miRNAs encoded by CvBV can be 100-fold greater in parasitized hosts than non-parasitized ones. We further show that one teratocyte-produced miRNA (Cve-miR-281-3p) and one CvBV-produced miRNA (Cve-miR-novel22-5p-1) arrest host growth by modulating expression of the host ecdysone receptor (EcR). Altogether, our results show the first evidence of cross-species regulation by miRNAs in animal parasitism and their possible function in the alteration of host physiology during parasitism.