A prognostic model constructed by ferroptosis-associated genes (FAGs) in papillary renal cell carcinoma (PRCC) and its association with tumor mutation burden (TMB) and immune infiltration.

BACKGROUND: This study aimed to identify the prognostic-related differentially expressed ferroptosis-associated genes (DEFAGs) in papillary renal cell carcinoma (PRCC). METHODS: Data encompassing simple nucleotide variation, transcriptome profiles, and relevant clinical information of PRCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The expression matrix of ferroptosis-associated genes (FAGs) was analyzed using the "limma" package in R to identify differentially expressed DEFAGs. Lasso regression analysis, along with univariate and multivariate Cox proportional hazards regressions, was employed to identify independent prognostic-related DEFAGs and formulate a nomogram. Additionally, we examined potential independent survival-related clinical risk factors and compared immune cell infiltration and tumor mutation burden (TMB) differences between high- and low-risk patient groups. RESULTS: A cohort of 321 patients were analyzed, revealing twelve FAGs significantly influencing the overall survival (OS) of PRCC patients. Among them, two mRNAs (GCLC, HSBP1) emerged as independent prognostic-related DEFAGs. Smoking status, tumor stage, and risk score were identified as independent clinical risk factors for PRCC. Furthermore, notable disparities in immune cell infiltration and function were observed between high- and low-risk groups. GCLC and HSBP1 were associated with various immune cells and functions, TMB, and immune evasion. CONCLUSION: This finding revealed two independent prognostic-related DEFAGs in PRCC and established a robust prognostic model, offering potential therapeutic targets and promising insights for the management of this disease.

Di-(2-ethylhexyl) phthalate promotes benign prostatic hyperplasia through KIF11-Wnt/ß-catenin signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts reporting an association between DEHP exposure and BPH, its underlying mechanisms have not been investigated. Our findings indicate that exposure to DEHP or MEHP (main metabolites of DEHP in the human body) leads to increased prostate weights, elevated prostate index, and notable epithelial thickening in rats. It has been observed to promote BPH-1 cell proliferation with effects ranging from low to high concentrations. Transcriptome sequencing analysis of rat prostate tissues identified KIF11 as the key hub gene. KIF11 is highly expressed after DEHP/MEHP exposure, and knocking down of KIF11 inhibits the MEHP-induced promotion of cell proliferation. Exposure to MEHP has been observed to increase the expression of p-GSK-3ß and elevate the levels of ß-catenin, thereby activating the Wnt/ß-catenin signaling pathway. Knocking down of KIF11 significantly inhibits these effects. Histone H3 at Lysine 27 acetylation (H3K27ac) is implicated in the upregulation of KIF11 expression, as evidenced by the addition of the acetylation inhibitor C646. In summary, our findings established that DEHP exposure could promote BPH through H3K27ac regulated KIF11/Wnt/ß-catenin signaling pathway.

HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells.

BACKGROUND/AIM: The underlying processes of renal cell carcinoma (RCC), one of the deadliest malignancies of the urinary system, are still poorly understood. HECT domain E3 ubiquitin protein ligase 2 (HECTD2) is an E3 ubiquitin ligase implicated in the pulmonary inflammatory response. This study investigated the impact of HECTD2 on regulating inflammation in RCC cells and its potential mechanisms. MATERIALS AND METHODS: HECTD2 expression in RCC tissues was examined. Immunoprecipitation and western blot (WB) analysis confirmed that HECTD2 up-regulated euchromatic histone lysine methyltransferase 2 (EHMT2) protein degradation. ChIP experiments validated tumor necrosis factor α Inducing protein 1 (TNFAIP1) as a direct target of EHMT2. qRT-PCR determined HECTD2 and TNFAIP1 expression in RCC cells. Cell viability was assayed via CCK-8. ELISA was employed to measure the expression of IL-6, TNF-α, IL-8, and IL-1ß. WB analysis was conducted to test p38/JNK pathway-related protein (p38, p-p38, JNK, and p-JNK) expression. RESULTS: HECTD2 and TNFAIP1 were significantly up-regulated in RCC patient tissues and cells. Subsequent investigations revealed that HECTD2 promoted an inflammatory response in RCC cells. Additionally, HECTD2 up-regulated TNFAIP1 expression, and high TNFAIP1 expression could reverse the repressive impact of low HECTD2 expression on the inflammatory response in RCC cells. Rescue experiments demonstrated that the addition of p38/JNK pathway inhibitors attenuated the impact of TNFAIP1 overexpression on the RCC inflammatory response. CONCLUSION: Our findings establish a new mechanism by which HECTD2 exerts a pro-inflammatory role in RCC cells and present a prospective method for an anti-inflammatory intervention targeting the HECTD2/TNFAIP1 axis in malignancies.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

The Influence of Tourist Attraction Type on Product Price Perception and Neural Mechanism in Tourism Consumption: An ERP Study.

Background: Tourism consumption is a topic with heated debates in tourism research, and pricing tourism products is a crucial task for tourism managers. Different types of tourist attractions offer different experiences to tourists, which affect their price perceptions and purchase decisions. Methods: This study combined questionnaires and event-related potentials (ERPs) measures to explore the magnitude of psychological conflict and the degree of emotional arousal that consumers experience when faced with different prices of goods in different scenic types. Results: The questionnaire results showed that attraction type influenced consumers' price perceptions and that consumers were willing to pay higher prices for products in attractions. The ERP results implied that in the early stage of cognition, attraction type did not affect consumers' perceptual processing, while price information attracted consumers' cognitive attention. In the late stage of cognition, attraction type, and price information jointly influenced consumers' decision-making, and consumers tended to accept high prices of products in entertainment attractions and cultural attractions, but consumers were more sensitive to the price of products in cultural attractions and less tolerant to price increases. Conclusion: The study elucidated how price information influenced consumers' purchase decisions of tourism products at different stages of the dual-process theory, which can assist tourism managers in devising different pricing strategies and positioning strategies based on the attributes of attractions, to enhance product sales and revenues. This would further the vision of the World Tourism Organization (UNWTO) of "tourism fostering economic development".

Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients.

Background: Schizophrenia (SCZ) is a serious chronic mental disorder. Our previous case-control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study. Methods: Genotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR. Results: Based on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137. Conclusion: The plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future.

A pan-cancer analysis reveals the diagnostic and prognostic role of CDCA2 in low-grade glioma.

BACKGROUND: Cell division cycle associated 2 (CDCA2), a member of the cell division cycle associated proteins (CDCA) family, is crucial in the regulation of cell mitosis and DNA repair. CDCA2 was extensively examined in our work to determine its role in a wide range of cancers. METHODS: CDCA2 differential expression was studied in pan-cancer and in diverse molecular and immunological subgroups in this research. Additionally, the diagnostic and prognostic significance of CDCA2 in pan-cancer was also evaluated using receiver operating characteristic (ROC) and Kaplan-Meier (KM) curves. Prognostic value of CDCA2 in distinct clinical subgroups of lower grade glioma (LGG) was also investigated and a nomogram was constructed. Lastly, potential mechanisms of action of CDCA2 were interrogated including biological functions, ceRNA networks, m6A modification and immune infiltration. RESULTS: CDCA2 is shown to be differentially expressed in a wide variety of cancers. Tumors are diagnosed and forecasted with a high degree of accuracy by CDCA2, and the quantity of expression CDCA2 is linked to the prognosis of many cancers. Additionally, the expression level of CDCA2 in various subgroups of LGG is also closely related to prognosis. The results of enrichment analyses reveal that CDCA2 is predominantly enriched in the cell cycle, mitosis, and DNA replication. Subsequently, hsa-miR-105-5p is predicted to target CDCA2. In addition, 4 lncRNAs were identified that may inhibit the hsa-miR-105-5p/CDCA2 axis in LGG. Meanwhile, CDCA2 expression is shown to be associated to m6A-related genes and levels of immune cell infiltration in LGG. CONCLUSION: CDCA2 can serve as a novel biomarker for the diagnosis and prognosis in pan-cancer, especially in LGG. For the development of novel targeted therapies in LGG, it may be a potential molecular target. However, to be sure, we'll need to do additional biological experiments to back up our results from bioinformatic predictions.

Ent-eudesmane sesquiterpenoids from the Chinese liverwort Chiloscyphus polyanthus.

- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.

Status of pediatric echocardiography clinical trials: a cross-sectional study of registered trials in ClinicalTrials.gov.

Background: The objective of this study is to analyze the characteristics of pediatric echocardiography clinical trials registered in ClinicalTrials.gov. Methods: A data set including pediatric echocardiography clinical trials was downloaded from ClinicalTrials.gov until May 13, 2022. We searched the PubMed, Medline, Google Scholar, and Embase databases to extract publication data. Pediatric echocardiography trial characteristics, application areas, and publication status were described. The secondary objectives were to evaluate factors associated with trial publication. Results: We identified 410 pediatric echocardiography reporting definite age, of which 246 were interventional and 146 were observational. Drug interventions were the most commonly studied (32.9%). The most applied area of pediatric echocardiography was congenital heart disease, followed by hemodynamics of preterm or neonatal infants, cardiomyopathy, inflammatory heart disease, pulmonary hypertension, and cardio-oncology. According to the primary completion data, 54.9% of the trials were completed before August 2020. 34.2% of the trials had been published within 24 months. Union countries and quadruple masking were more likely to be published. Conclusion: Echocardiography is rapidly evolving in pediatric clinical applications, including anatomic imaging and functional imaging. Novel speckle tracking techniques have also been pivotal in the assessment of cancer therapeutics-related cardiac dysfunction. A small number of clinical trials in pediatric echocardiography are published in a timely fashion. Concerted efforts are needed to promote trial transparency.

The hub genes and their potential regulatory mechanisms in chronic spontaneous urticaria revealed by integrated transcriptional expression analysis.

Chronic spontaneous urticaria (CSU) is a recurrent disease characterized by wheals and or angioedema, and its pathogenesis is still unclear. The microarray datasets of skin tissue from CSU patients and healthy controls were integrated and analysed in Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the NetworkAnalyst tool. Then, the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Subsequently, a protein-protein interaction (PPI) network of DEGs was constructed by STRING and the related hub genes were identified through the MOCDE tool. The potential miRNAs targeting hub genes were predicted based on the intersection of three online databases, namely TargetScanHuman, TargetBase and miRNet. Differentially expressed lncRNAs (DElncRNAs) was performed using the GEO2R tool. The potential miRNAs targeting DElncRNAs were predicted through miRNet. Finally, the shared miRNAs targeting both hub genes and DElncRNAs were used to construct an mRNA/miRNA/lncRNA regulatory network. A total of 296 DEGs were obtained, which were mainly enriched in inflammatory and immune responses. Further, 14 hub genes were identified by the PPI network of DEGs. Clinical correlation analysis showed that the mRNA expressions of S100A7, S100A8, S100A9, S100A12, IL6 and SOCS3 in CSU were positively correlated with the 7-day urticaria activity score (UAS7), and their potential diagnostic value was supported by the receiver operating characteristic curve (ROC) analysis. Five up-regulated lncRNAs in the cytoplasm were obtained by DElncRNAs analysis. The ROC analysis showed that PVT1, SNHG3 and ZBTB20 - AS1 was of potential diagnostic value for CSU. Eight shared miRNAs targeting both hub genes and DElncRNAs were identified and used to construct a competing endogenous RNA (ceRNA) network. It was found that the IL-6/miR - 149 - 5p/ZBTB20 - AS1 axis might play an important role in the activation of mast cells in CSU. IL-6 and its related regulatory molecules may be used as potential diagnostic markers and therapeutic targets for CSU.

Advances in highly active one-carbon metabolism in cancer diagnosis, treatment and drug resistance: A systematic review.

Study background objectives: Cancer poses a significant health concern as it is incurable. Every year, research on how to treat and eradicate this chronic condition is done. This systematic review will unmask the recent developments concerning highly active 1C metabolism with regard to cancer diagnosis, treatment, and drug resistance. The significance of this study is rolling out evidence-based evidence on the importance of one-carbon metabolism in cancer diagnosis and treatment. Methods: Eight randomized controlled trials (RCTs) were reviewed from five electronic databases - EMBASE, Scopus Review, Google Scholar, Web of Science, and PubMed. Outcomes from the eight studies were analyzed to paint a picture of the topic in question. While the Preferred Reporting Items for Systematic Reviews and Meta-Analysis' (PRISMA) protocol guided the initial literature search, The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach informed quality assessments of the eligible studies. Conclusion: Since its emergence in the 1980s, 1C metabolism has been investigated and broadened to capture essential aspects of cancer treatment, diagnosis, and drug resistance. The review found that metabolites like folic acid could be used to detect different types of cancer. The metabolic pathways could induce tumorigenesis and DNA methylation, hence drug resistance. Systematic review registration: https://inplasy.com/projects/, identifier INPLASY2022110099.

Tumor suppressive role of microRNA-139-5p in bone marrow mesenchymal stem cells-derived extracellular vesicles in bladder cancer through regulation of the KIF3A/p21 axis.

The emerging roles of extracellular vesicles (EVs) in bladder cancer have recently been identified. This study aims to elucidate the role of microRNA-139-5p (miR-139-5p) shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived EVs (BMSCs-EVs) in bladder cancer, with the possible mechanism explored. Expression of miR-139-5p and KIF3A was tested, followed by an analysis of their correlation. EVs were isolated from BMSCs and co-cultured with T24 or BOY-12E cells with miR-139-5p mimic/inhibitor, oe-KIF3A, and/or si-p21 transfected to study the roles of miR-139-5p/KIF3A/p21 in bladder cancer cell functions. A nude mouse model of subcutaneous xenograft tumor was constructed to detect the effect of miR-139-5p in BMSCs-EVs on the tumorigenesis and lung metastasis of bladder cancer cells in vivo. It was identified that miR-139-5p was highly expressed in BMSCs-EVs, but poorly expressed in bladder cancer. BMSCs-EVs transferred miR-139-5p into bladder cancer cells where miR-139-5p inhibited the malignant features of bladder cancer cells in vitro. miR-139-5p in BMSCs-EVs targeted KIF3A and inhibited the expression of KIF3A, thereby activating p21. miR-139-5p in BMSCs-EVs arrested the tumorigenesis and lung metastasis of bladder cancer cells in vivo by modulation of the KIF3A/p21 axis. Altogether, BMSCs-EVs carried miR-139-5p targeted KIF3A to activate p21, thus delaying the occurrence of bladder cancer.

METTL14-mediated epitranscriptome modification of MN1 mRNA promote tumorigenicity and all-trans-retinoic acid resistance in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N6-methyladenosine (m6A) modification plays a critical role in influencing RNA fate. However, the biological significance of m6A modification and its potential regulatory mechanisms in the development of OS remain unclear. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m6A levels. Western blotting, quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC) were used to investigate METTL14 expression levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL14. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to explore the specific binding of target genes and relevant m6A "readers". RNA stability and polysome analysis assays were used to detect the half-lives and translation efficiencies of the downstream genes of METTL14. IHC and clinical data were applied to explore the clinical correlations of METTL14 and its downstream target genes with the prognosis of OS. FINDINGS: We observed the abundance of m6A modifications in OS and revealed that METTL14 plays an oncogenic role in facilitating OS progression. MeRIP-seq and RNA-seq revealed that MN1 is a downstream gene of METTL14. MN1 contributes to tumor progression and all-trans-retinoic acid (ATRA) chemotherapy resistance in OS. Mechanistically, MN1 is methylated by METTL14, specifically in the coding sequence (CDS) regions, and this modification is recognized by the specific m6A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to prevent MN1 mRNA degradation and promote it translation efficiency. IHC showed that MN1 expression was positively correlated with METTL14 and IGF2BP2 expression in OS tissues. The METTL14-IGF2BP2-MN1 panel demonstrated more promising prognostic value for OS patients than any of these molecules individually. INTERPRETATION: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m6A RNA methylase by regulating the stability and translation efficiency of MN1 and thus provides both an underlying biomarker panel for prognosis prediction in OS patients. FUNDING: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864).

Focal facial dermal dysplasias type III: Two families with Setleis syndrome in China.

Focal facial dermal dysplasias type III (FFDD III), commonly known as Setleis syndrome (SS; Online Mendelian Inheritance in Man #227260), is a type of focal facial dermal dysplasia, characterized by bitemporal atrophic skin lesion. The homozygous mutations in the TWIST2 gene and copy number variants (CNV) at chromosome 1p36.22p36.21 were reported as the pathogenic mechanism. In this study, we collected DNA samples from a large Chinese family affected by FFDD and found no mutation of TWSIT2. To determine the underlying genetic cause, we performed a multipoint parameter linkage analysis and haplotype analysis of the family 1 and mapped SS to a region Chr1:14.074-20.524cM (rs2401090-rs2294642). Copy number variant was identified by Sanger sequencing, which breakpoints were Chr1:11695972 and Chr1:11829858. The region contains eight genes, including FBXO2, FBXO44, FBXO6, MAD2L2, DRAXIN, AK125437, AGTRAP, and C1orf167. There were no candidate gene mutations of the second family with SS. Our study further reduced the size of CNV resulting in SS (Chr1:11696993-11829858) and focused on eight genes.

A diagnostic test: diagnostic value of gastrointestinal endoscopy narrow-band imaging (NBI) for colorectal laterally spreading tumor (LST) and submucosal invasion.

Background: Endoscopic ultrasonography is an effective endoscopic examination method for determining the depth of colorectal cancer invasion. Narrow-band imaging (NBI) techniques increase the contrast of vascular structures and more clearly highlight subtle structures on mucosal surfaces, thereby improving the accuracy of endoscopic assessment. This study investigated the diagnostic efficacy of NBI in colorectal laterally spreading tumor (LST) and its submucosal invasion. Methods: A total of 224 patients with colorectal LST admitted to the Affiliated Hospital of Putian University from January 2015 to December 2021 were enrolled in this study. The patients were divided into NBI and endoscopic ultrasonography groups according to the different examination methods they received. Subsequently, the clinicopathological characteristics of the patients were collected, and the rates of submucosal invasion of the four subtypes (LST-G-H, LST-G-NM, LST-NG-F, LST-NG-PD) were compared between the two groups. Also, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of judging the depth of LST lesions of the two examination methods were compared, taking the results of pathological tissue examination as the gold standard. Results: This study enrolled 224 patients with LST (mean onset age: 57.98±6.48 years), including 123 males and 101 females. In terms of tumor location, 21 cases were located in the cecum, 22 cases in the ascending colon, 38 cases in the transverse colon, 11 cases in the descending colon, 12 cases in the descending sigmoid junction, 23 cases in the sigmoid colon, and 97 cases in the rectum. The sizes of the tumors ranged from 18.81 to 52.88 mm. Moreover, there were 21 cases of lesion infiltration into the submucosa, and the infiltration rate was 9.38%. Furthermore, the accuracy of NBI in diagnosing colorectal LST was significantly higher than that of endoscopic ultrasonography (87.05% vs. 57.14%); NBI was more accurate than endoscopic ultrasonography in the preoperative diagnosis of LST lesion depth in the rectal, non-rectal, granular (LST-G), non-granular (LST-NG), <40, and ≥40 mm groups. Conclusions: Gastrointestinal NBI has a superior accuracy rate and value than endoscopic ultrasonography in diagnosing colorectal LST, tumor lesion depth, and submucosal invasion. Therefore, gastrointestinal NBI deserves to be promoted in clinical work.

Kirsten rat sarcoma viral oncogene homolog G12C mutant advanced non-small-cell lung cancer treated with MEK1/2 inhibitor trametinib: a case report.

No targeted therapies are approved for non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation to date. Trametinib, a selective allosteric inhibitor of the MEK1/2, demonstrated debatable clinical activity in KRAS-mutant NSCLC. In this case, we present a recurrent advanced NSCLC with KRAS G12C mutation successfully treated with single-agent trametinib therapy. An 87-year-old man who underwent radiotherapy for the right lung adenocarcinoma was admitted to clinical oncology center for recurrent lesions in bilateral lungs. He was unwilling to perform second-line chemotherapy, but underwent molecular profiling and revealed the KRAS G12C mutation. The single-agent target therapy of trametinib showed clinical benefit without obvious toxicity. Furthermore, this report reviewed the previous date of the preclinical and clinical and summarized that KRAS G12C mutation may be more sensitive to the inhibition of mitogen-activated protein kinase kinase. This case advocates for routine screening of KRAS point mutations in the utility of precision medicine and suggests that treatment with trametinib in advanced NSCLC cases with KRAS G12C mutation is well tolerated and effective, especially for those very elderly or unsuitable for more aggressive chemotherapy.

Expanding the clinical spectrum of anti-IgLON5 disease: A multicenter retrospective study.

BACKGROUND: We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti-IgLON5 disease. METHODS: We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow-up outcomes. RESULTS: The median age of onset for symptoms was 60 (range: 33-73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein-Barr virus (EBV)-related anti-IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow-up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2). CONCLUSIONS: The clinical spectrum of anti-IgLON5 disease is variable. Our results highlight a boarder spectrum of anti-IgLON5 disease.

Design, synthesis and antiproliferative activity of novel 2,4-diamino-5-methyleneaminopyrimidine derivatives as potential anticancer agents.

In order to discover new anticancer agents, 25 novel 2,4-diamino-5-methyleneaminopyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Among them, compared with 5-FU, compound 7i exhibited 4.9-, 2.9-, 2.1-, and 3.0-fold improvement in inhibiting HCT116, HT-29, MCF-7, and HeLa cells proliferation with IC50 values of 4.93, 5.57, 8.84, and 14.16 µM, respectively. Moreover, further mechanistic studies indicated that compound 7i could concentration-dependently induce cell cycle arrest and apoptosis in HCT116 cells. These findings revealed that 2,4-diamino-5-methyleneaminopyrimidine scaffold has potential for further investigation to explore novel anticancer agents.

Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines.

By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.

Triple administration of osimertinib followed by chemotherapy for advanced lung adenocarcinoma: A case report.

BACKGROUND: Osimertinib is the recommended first-line treatment for adult patients with epidermal growth factor receptor (EGFR) mutation positive advanced or metastatic non-small cell lung cancer (NSCLC). However, primary or acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) seems inevitable, and when drug-resistance occurs during treatment with osimertinib, the standard of care is to discontinue the TKI. CASE SUMMARY: A 57-year-old female patient with lung adenocarcinoma presented with an irritating cough accompanied by chest distress of one month duration. An enhanced head magnetic resonance imaging scan showed brain metastases. An EGFR mutation (exon 21 L858R) was detected in pleural fluid. The patient was treated with oral osimertinib (80 mg once daily) from January 2018 but developed progressive disease on December 2018. She was then successfully treated with re-challenge and tri-challenge with osimertinib (80 mg once daily) by resensitization chemotherapy twice after the occurrence of drug-resistance to osimertinib, and to date has survived for 31 mo. CONCLUSION: This case may provide some selective therapeutic options for NSCLC patients with acquired drug-resistance who were previously controlled on osimertinib treatment.