Bioinformatics analysis identifies DYNC1I1 as prognosis marker in male patients with liver hepatocellular carcinoma.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is one of the most common malignant tumors. However, the etiology and exact molecular mechanism of LIHC are still not fully understood, which makes it urgent for us to further study the molecular events behind. METHODS: In this study, differences in mRNA expression between LIHC samples and normal adjacent samples were found through analyzing the TCGA database, and key targets were sought. We analyzed 371 LIHC samples and 50 normal adjacent samples according to P <0.01 and logFC>2.5, a total of 1092 genes were identified differentially expressed, including 995 up-regulated genes and 97 down-regulated genes. We predicted the interactions of these differentially expressed mRNAs, and used Cyto-Hubba to locate the hub gene-dynein cytoplasmic 1 intermediate chain 1 (DYNC1I1). RESULTS: Survival analysis showed that DYNC1I1 was a prognostic factor for LIHC male patients. Functional enrichment indicated that DYNC1I1 and differentially expressed interacting proteins were involved in the cell cycle. CONCLUSION: In conclusion, this study discovers that DYNC1I1 can be used as a prognostic marker for LIHC male patients.

Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

Combined detection of circulating tumor cells, α-fetoprotein heterogene-3 and α-fetoprotein in the early diagnosis of HCC for the prediction of efficacy, prognosis, recurrence after microwave ablation.

BACKGROUND: Early diagnosis can significantly improve treatment outcomes for hepatocellular carcinoma (HCC) patients. Currently, the dosage of serum alpha fetoprotein (AFP) is widely used in the diagnosis of HCC, but this biomarker has low specificity and may cause false positive or false negative results. Thus, it's necessary to find and validate other serum tumor markers that in association for AFP would increase the sensitivity and the specificity in the HCC diagnosis. This study investigated the predictive value of combined of AFP, AFP-L3, and Circulating tumor cells (CTCs). METHODS: A total of 105 patients with HCC after microwave ablation (MWA) were divided into non recurrence group, recurrence group, good prognosis (CR + PR group, CR: Complete remission, PR: Partial remission) and poor prognosis (SD + PD group, SD: Stable, PD: Progression). ROC curve was used to analyze the short-term efficacy, prognosis and clinical value of combined detection of the three indicators in predicting postoperative recurrence of HCC patients with MWA. RESULTS: The positive rate of serum CTCs, AFP-L3 and AFP combined detection in the diagnosis of HCC is higher than that of single index and two index detection. The AUC, sensitivity and specificity of serum CTCs, AFP-L3 and AFP combined detection was better than that of single index and two indexes in patients with HCC after MWA. CONCLUSIONS: Combined detection of AFP, AFP-L3, and CTCs can effectively make up for the shortcomings of the detection with single and pairwise indicators. It can't only diagnose HCC in early, but also has a high clinical value of predicting the short-term efficacy, prognosis and recurrence of HCC patients after MWA treatment.