High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis.

BACKGROUND: To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited. METHODS: In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform. FINDINGS: We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia. INTERPRETATION: We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule. FUNDING: This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

The short- and long-term readmission of four major categories of digestive system cancers: does obesity or metabolic disorder matter?

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC. Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox regression analysis was used to estimate the effect of metabolic obesity phenotypes on DSC readmission. Results: The MUNO phenotype had 1.147-fold (95% CI: 1.066, 1.235; p < 0.001) increased 180-day readmission risks in patients with neoplasm of the upper digestive tract. The MUNO phenotype had 1.073-fold (95% CI: 1.027, 1.121; p = 0.002) increased 30-day readmission risks and 1.067-fold (95% CI: 1.021, 1.115; p = 0.004) increased 180-day readmission risks in patients with neoplasm of the lower digestive tract. The MUNO and MUO phenotypes were independent risk factors of readmission in patients with liver or pancreatic neoplasm. Metabolic obesity status was independently associated with a high risk of severe and unplanned hospitalization within 30 days or 180 days. Conclusion: Both obesity and metabolic abnormalities are associated with a high risk for the poor prognosis of DSC patients. The effect of metabolic categories on the short- or long-term readmission of liver or pancreas cancers may be stronger than that of obesity.

Clinical Efficacy Evaluation and Potential Mechanism of Zhishe Tongluo Capsule in the Treatment of Cerebral Infarction by Meta-Analysis Associated with Network Pharmacology.

OBJECTIVE: By integrating meta-analysis and network pharmacology strategy, the clinical efficacy of Zhishe Tongluo capsule in the treatment of cerebral infarction was evaluated, and the intervention mechanism was preliminary explored. METHODS: Through meta-analysis, the Chinese and English literature of the randomized controlled trial (RCT) of Zhishe Tongluo capsule in the treatment of cerebral infarction was comprehensively searched. Based on the standard of Na Pai, the quantitative literature was determined and the Review Manager data were statistically analyzed. RESULTS: A total of 10 RCTs literatures were included. These literatures included a total of 1278 subjects, of which 670 were in the treatment group and 608 were in the control group. In terms of indicators of efficiency and adverse reaction rate, the treatment group was better than the control group. There was a statistical difference (P < 0.05); a total of 559 chemical constituents and 2306 potential targets were obtained from the online database. Of these, 201 components, 145 targets, and 185 pathways were closely related to cerebral infarction. CONCLUSIONS: The available evidence indicates that the addition of Zhishe Tongluo capsule to the conventional treatment of Western medicine can improve the clinical efficacy of cerebral infarction and has some advantages in regulating blood lipids and hemorheology, but the overall evidence level is low, which still needs to be further supported by large-scale and multicenter RCTs; intervention of brain infarction by Zhishe Tongluo capsule is a comprehensive result of multicomponent and multi-target interactions. On the basis of the combined meta-analysis and network pharmacology in scientific attempts, it also provides a reference for the clinical evaluation of other drugs and mechanism research.

Identification of the Signature Associated With m6A RNA Methylation Regulators and m6A-Related Genes and Construction of the Risk Score for Prognostication in Early-Stage Lung Adenocarcinoma.

BACKGROUND: N6-methyladenosine (m6A) RNA modification is vital for cancers because methylation can alter gene expression and even affect some functional modification. Our study aimed to analyze m6A RNA methylation regulators and m6A-related genes to understand the prognosis of early lung adenocarcinoma. METHODS: The relevant datasets were utilized to analyze 21 m6A RNA methylation regulators and 5,486 m6A-related genes in m6Avar. Univariate Cox regression analysis, random survival forest analysis, Kaplan-Meier analysis, Chi-square analysis, and multivariate cox analysis were carried out on the datasets, and a risk prognostic model based on three feature genes was constructed. RESULTS: Respectively, we treated GSE31210 (n = 226) as the training set, GSE50081 (n = 128) and TCGA data (n = 400) as the test set. By performing univariable cox regression analysis and random survival forest algorithm in the training group, 218 genes were significant and three prognosis-related genes (ZCRB1, ADH1C, and YTHDC2) were screened out, which could divide LUAD patients into low and high-risk group (P < 0.0001). The predictive efficacy of the model was confirmed in the test group GSE50081 (P = 0.0018) and the TCGA datasets (P = 0.014). Multivariable cox manifested that the three-gene signature was an independent risk factor in LUAD. Furthermore, genes in the signature were also externally validated using the online database. Moreover, YTHDC2 was the important gene in the risk score model and played a vital role in readers of m6A methylation. CONCLUSION: The findings of this study suggested that associated with m6A RNA methylation regulators and m6A-related genes, the three-gene signature was a reliable prognostic indicator for LUAD patients, indicating a clinical application prospect to serve as a potential therapeutic target.