Abstract Background Prostate cancer (PCa) is currently the major malignancy in men. It is becoming increasingly clear that competitive endogenous RNA (ceRNA) regulation networks are important in a wide variety of cancers. Nevertheless, there is still much to learn about the biological functions of the ceRNA network in prostate cancer. Methods The ceRNA network was constructed using the "GDCRNATools" package. Based on survival analysis, we obtained AC005154.6/hsa-miR-29c-3p/CCNL2 for further analysis. The prognostic model based on this ceRNA network was constructed by univariate and multivariate Cox regression methods. Furthermore, functional enrichment analysis, mutation landscape analysis, immune infiltration analysis, drug sensitivity analysis, methylation analysis, pan-cancer analysis, and molecular experiments of CCNL2 were carried out to investigate the role of CCNL2 in tumorigenesis. Results We identified the AC005154.6/CCNL2 axis as a risk factor that can promote the progression of prostate cancer by bioinformatics analysis and molecular experiments. Immune infiltration analysis suggested that CCNL2 may act as a novel biomarker for treatment decisions. The methylation level of CCNL2 was significantly decreased in tumor samples, possibly contributing to the upregulation of CCNL2 in prostate cancer. Moreover, CCNL2 is differentially expressed in multiple cancers and is tightly correlated with immune infiltration. Conclusion The current study constructed a ceRNA network, AC005154.6/hsa-miR-29c-3p/CCNL2. Potentially, this biomarker can be used for early diagnosis and decision-making about prostate cancer treatment.
US-guided microwave ablation was safe and effective in treating patients with Bethesda category III thyroid nodules with negative polygenic panel tests and did not increase the risk of tumor progression.
Gene expression profiles of blood can reflect the physiopathologic status of the immune system. The dynamic microRNA (miRNA) expression profiles of peripheral blood from pigs at different developmental stages, and how differential expression of miRNAs might relate to immune system development, are unknown. In this study, peripheral blood samples taken at five developmental stages were used to construct 15 miRNA libraries (three biological replicates/stage): 0 days (newborn), 30 days (weaning), 60 days (weaned), and 180 and 360 days (puberty). We identified 295 known mature miRNAs. Hierarchical clustering of the miRNA expression profile showed significant differences between individuals at the neonatal and postnatal stages. Functional enrichment analysis revealed that miRNAs differentially expressed between pairwise comparisons of the developmental stages were over-represented in immune-related pathways such as toll-like receptor signaling. The time-course of expression of the over-representated miRNAs exhibited a pattern of steady decline over time, for both the complete miRNA compendium and immune-related miRNAs. We identified six marker miRNAs that were highly negatively correlated with chronologic age and enriched for genes involved in immune-related pathways. This study of a peripheral blood miRNA transcriptome offers insight into immune system development in swine and provides a resource for pig genome annotation.
To the Editor: The latest variant of concern, Omicron, has become the dominant global variant immediately after it was first reported in November 2021.[1] It contains >30 mutations in the spike protein, with 17 mutations in the receptor-binding domain, rendering it with increased transmissibility and capacity for immune evasion.[1,2] Moreover, the waning of protection has been observed over time since the coronavirus disease 2019 (COVID-19) vaccination.[3] Therefore, a booster is highly recommended. A large-scale study in the UK assessing the effectiveness of the booster vaccination with either the BNT162b2 or mRNA-1273 indicated that the booster shot substantially increased protection against symptomatic infection in patients with the confirmed Omicron variant infection.[3] However, although the laboratory study has illustrated that the homologous booster with the inactivated COVID-19 vaccine could also yield potent neutralizing activity against the Omicron variant,[4] clinical evidence regarding the effectiveness of this vaccination program is limited. To estimate the protective effect (PE) of the homologous booster vaccination program against severe to critical diseases, we conducted a retrospective cohort study by including adult symptomatic patients infected with the Omicron subvariant (BA.2) during the outbreak of COVID-19 in the Jilin province (13 March–20 April, 2022). Vaccination status was extracted from the provincial immunization management system. Patients were categorized into unvaccinated, partially vaccinated (PV), fully vaccinated (FV), and the booster group based on their vaccination status. The primary outcome was the PE of the inactivated COVID-19 vaccine against severe to critical COVID-19 which was estimated by calculating the risk ratio in each group in reference to the unvaccinated group with univariate and multivariate logistic regression and subtracted from one. The ethics committee in the Jilin Central General Hospital approved the study (No. 2022–135). There were 3604 symptomatic patients with the Omicron subvariant (BA.2) infection included in the final analysis. One thousand and ninty-five (30.4%) of patients completed the primary vaccine course, 1052 (29.2%) received the booster vaccination, 926 (25.7%) of patients only received the first dose, and 530 (14.7%) did not receive any vaccine. Patients in the booster vaccination group all received homologous boosters. During their hospitalization, 116 (3.2%) patients developed severe to critical infection, with 54 (10.2%) in the unvaccinated group, 29 (3.1%) in the PV group, 29 (2.6%) in the FV group, and 4 (0.4%) in the booster group, respectively [Supplementary Table 1, https://links.lww.com/CM9/B579]. In terms of the PE of the inactivated vaccine, the unadjusted effectiveness against severe to critical disease was 69.4% (95% confidence interval [CI], 52.6–80.3%) in PV patients, 74.1% (95% CI, 59.8–83.3%) in FV patients and 96.3% (95% CI, 89.8–98.6%) in patients with a booster vaccination. After adjusting for age and comorbidity, the PE was slightly lower than that of unadjusted but with a similar trend. The booster vaccination presented the highest protection against severe to critical disease (93.8%, 95% CI, 82.7–97.8%) [Figure 1].Figure 1: PE of the inactivated COVID-19 vaccine against severe to critical disease caused by the omicron variant. The unadjusted PE of the inactivated COVID-19 vaccine against severe to critical illness caused by the omicron variant was 69.4% (95% CI, 52.6–80.3%) in PV patients, 74.1% (95% CI, 59.8–83.3%) in FV patients and 96.3% (95% CI, 89.8–98.6%) in patients with a booster vaccination. After adjusting for age and comorbidity, the adjusted PE was 54.6% (95% CI, 28.9–71.1%) in PV patients, 64.8% (95% CI, 45.0–77.5%) in FV patients and was 93.8% (95% CI, 82.7–97.8%) in patients with a homologous booster shot. CI: Confidence interval; FV: Fully vaccinated; PE: Protective effect; PV: Partially vaccinated.In the present study, we demonstrated that the homologous booster with the inactivated COVID-19 vaccine is effective in controlling the severity of the Omicron infection, as the adjusted PE against severe to critical illness reached 93.8% (95% CI, 82.7–97.8%). The results were similar to that reported in a large-scale study in Hong Kong, China, in which patients receiving boosters demonstrated a very high level of protection against severe outcomes (PE, 98.1%, 95% CI, 97.1–98.8%).[5] However, there are still concerns and challenges in implementing this COVID-19 vaccination policy. The level of neutralizing antibodies against the Omicron variant in persons who received the inactivated COVID-19 vaccine was lower than those receiving the messenger RNA or adenoviral vector vaccine, even after the booster dose.[6] Moreover, a clinical study has already demonstrated the inferiority of the homologous booster with the inactivated COVID-19 vaccine in preventing infection and death during the prevalence of the Delta variant.[7] Therefore, it is rational to consider the possibility of implementing the heterogeneous program in China. There were several limitations in the present study. First, the current study design failed us directly to estimate the vaccine effectiveness of the homologous booster program. Although an excellent PE has been demonstrated in the present study, well-designed test-negative case–control studies are still warranted to analyze the actual vaccine effectiveness of the current homologous booster program in preventing Omicron infections. Second, we did not incorporate the duration between the last dose of the vaccine and the infection into the final analysis, which is an essential factor affecting the effectiveness of the COVID-19 vaccine. Third, the history of previous COVID-19 was unclear, which might underestimate the actual effectiveness of the booster vaccination because patients with previous infections were less likely to complete the COVID-19 vaccination. Finally, all the patients included in the present study were from a single center, so selection bias might have existed. Despite these limitations, results from the present study still offered evidence supporting the reasonability and necessity of implementing the current booster vaccination policy in China. Acknowledgments We thank Miao Wang (Sichuan University), Anxin He (Conch Hospital of Anhui Medical University), and Guanghui Chen (Conch Hospital of Anhui Medical University) for the constructive discussion of data analysis and vaccine policies. Funding The study was partially supported by grants from the Key Research and Development Project of the Science and Technology Department of Sichuan Province (No. 2021YFS0003, Zygd18020) and the High-level Talents Fund of the Wuhu Municipal Government (No. 2021–134). Conflicts of interest None.
ABSTRACT Background : The interrelation between the plasma proteome and plasma metabolome with sepsis presents a multifaceted dynamic that necessitates further research to elucidate the underlying causal mechanisms. Methods : Our investigation used public genome-wide association study data to explore the relationships among the plasma proteome, metabolome, and sepsis, considering different sepsis subgroup. Initially, two-sample Mendelian randomization established causal connections between the plasma proteome and metabolome with sepsis. Subsequently, multivariate and iterative Mendelian randomization analyses were performed to understand the complex interactions in plasma during sepsis. The validity of these findings was supported by thorough sensitivity analyses. Result : The study identified 25 plasma proteins that enhance risk and 34 that act as protective agents in sepsis. After P value adjustment (0.05/1306), ICAM5 emerged with a positive correlation to sepsis susceptibility ( P value = 2.14E-05, OR = 1.10, 95% CI = 1.05–1.15), with this significance preserved across three sepsis subgroup examined. Additionally, 29 plasma metabolites were recognized as risk factors, and 15 as protective factors for sepsis outcomes. After P value adjustment (0.05/997), elevated levels of 1,2,3-benzenetriol sulfate (2) was significantly associated with increased sepsis risk ( P value = 3.37E-05, OR = 1.18, 95% CI = 1.09–1.28). Further scrutiny revealed that this plasma metabolite notably augments the abundance of ICAM5 protein ( P value = 3.52E-04, OR = 1.11, 95% CI = 1.04–1.17), devoid of any detected heterogeneity, pleiotropy, or reverse causality. Mediated Mendelian randomization revealed ICAM5 mediated 11.9% of 1,2,3-benzenetriol sulfate (2)’s total effect on sepsis progression. Conclusion : This study details the causal link between the plasma proteome and metabolome with sepsis, highlighting the roles of ICAM5 and 1,2,3-benzenetriol sulfate (2) in sepsis progression, both independently and through crosstalk.
Over the years, molecular subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) status have been observed to effectively guide decision-making for the optimal treatment of patients with breast carcinoma (BRCA). However, despite this progress, there are still more than 41,000 BRCA-related fatalities each year in the United States. Moreover, effective drug targets for triple-negative breast carcinoma (TNBC) are still lacking. Given its high mortality rate, it is necessary to investigate more biomarkers with prognostic and pathological relevance in BRCA. In our study, we examined the expression patterns and prognostic implications of transmembrane P24 trafficking protein 9 (TMED9) in BRCA using multiple public cohorts and BRCA specimens collected from Shanghai General Hospital. In addition to this, in vitro experiments were also performed to evaluate the effects of TMED9 expression in BRCA cell proliferation and migration. Our results have demonstrated that a high expression of TMED9 promoted BRCA cell proliferation and migration and predicted poor prognosis in patients with BRCA. In conclusion, TMED9 is a potential prognostic indicator and a possible drug target of BRCA.
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