Study on the Clinical Implications of NLR and PLR for Diagnosing Frailty in Maintenance Hemodialysis Patients and Their Correlations with Patient Prognosis

Objective. To explore the clinical implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for diagnosing frailty in patients with maintenance hemodialysis (MHD) and their correlations with patient prognosis. Methods. A total of 185 patients with MHD admitted to the hemodialysis center of our hospital were selected, 72 of whom were diagnosed with frailty according to the Chinese version of Tilburg Frailty Indicator (TFI). The relevant data were collected, and the influencing factors of frailty in MHD patients were analyzed by one-way analysis of variance (ANOVA) and multivariate logistic regression. The value of NLR and PLR in diagnosing frailty in MHD patients was observed, and patients’ all-cause mortality was compared during the 3-year follow-up. The influences of different levels of NLR and PLR on the survival of MHD patients were investigated. Results. Multivariate regression analysis identified that serum albumin, dialysis adequacy, NLR, and PLR are independent risk factors for frailty in MHD patients ( P < 0.05 ). The area under the receiver operating characteristic (ROC) curve of NLR and PLR in diagnosing frailty in MHD patients was 0.859 and 0.799, respectively. Compared with the nonfrailty group, the 3-year mortality was higher, and the 3-year survival rate assessed by survival analysis was lower in the frailty group ( P < 0.05 ). Patients with high NLR and PLR levels showed a lower 3-year survival rate. Conclusions. Dialysis adequacy, serum albumin, NLR, and PLR are independently associated with frailty in MHD patients. NLR and PLR are of a certain diagnostic value for frailty in MHD patients. MHD patients with frailty have an unfavorable prognosis, as of those with high NLR and PLR levels.

Alpha-Fetoprotein Ratio Predicts Alpha-Fetoprotein Positive Hepatocellular Cancer Patient Prognosis after Hepatectomy

Background. This study was conducted to investigate the effect of alpha-fetoprotein (AFP) ratio on the prognosis of AFP-positive hepatocellular carcinoma (HCC) patients after hepatectomy. Methods. We retrospectively included 879 HCC patients with AFP-positive who underwent hepatectomy from February 2012 to October 2017 and randomly divided into training cohort and validation cohort. AFP ratio was equal to the AFP level within one week before hepatectomy to AFP level within 20-40 days after surgery. The end point of follow-up was disease-free survival (DFS) and overall survival (OS). Results. AFP ratio was not associated with clinical characteristics in training cohort and validation cohort. According to the X-tile software, the optimum cut-off point was 17.8 for AFP ratio. Significant differences between AFP ratio high and AFP ratio low were observed in DFS and OS in both cohort ( p < 0.05 ). Kaplan-Meier curves and receiver-operating curves were showed that AFP ratio was better than AFP level preoperation in predicting the prognosis of AFP-positive HCC patients after hepatectomy. The multivariate analysis demonstrated that AFP ratio was a significant independent risk factor for both OS and DFS in HCC patients with AFP-positive. Conclusions. AFP ratio might be a prognosis predictor for HCC patients with AFP-positive after hepatectomy.

CAMSAP1 Mutation Correlates With Improved Prognosis in Small Cell Lung Cancer Patients Treated With Platinum-Based Chemotherapy

Platinum-based chemotherapy is the first-line treatment for small cell lung cancer (SCLC). However, due to patients developing a resistance to the drug, most experience relapse and their cancer can become untreatable. A large number of recent studies have found that platinum drug sensitivity of various cancers is affected by specific gene mutations, and so with this study, we attempted to find an effective genetic biomarker in SCLC patients that indicates their sensitivity to platinum-based drugs. To do this, we first analyzed whole exome sequencing (WES) and clinical data from two cohorts to find gene mutations related to the prognosis and to the platinum drug sensitivity of SCLC patients. The cohorts used were the Zhujiang cohort (N = 138) and the cohort reported by George et al. (N = 101). We then carried out gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate possible molecular mechanisms through which these gene mutations affect patient prognosis and platinum drug sensitivity. We found that for SCLC patients, CAMSAP1 mutation can activate anti-tumor immunity, mediate tumor cell apoptosis, inhibit epithelial-mesenchymal transition (EMT), improve prognosis, and improve platinum drug sensitivity, suggesting that CAMSAP1 mutation may be a potential biomarker indicating platinum drug sensitivity and patient prognosis in SCLC.

COVID-19 Changed Prevalence, Disease Spectrum and Management Strategies of Ocular Trauma

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the health of people around the world and has reshaped social behaviors and clinical practice. The purpose of this perspective is to provide epidemiologists and clinicians with information about how the spectrum of ocular trauma diseases changed, as well as to optimize management for improving patient prognosis during this crisis. Analysis of current studies revealed that the prevalence of eye trauma decreased overall, with a trend of delayed medical treatment during the COVID-19 era. Irregular epidemic prevention and control measures, unprotected home activities, and unusual mental states are the main causes of ocular trauma. Strategies for reducing morbidity are also discussed, including popularizing the use norms of prevention and control supplies, taking heed to the safety of family activities, highlighting the special status of child protection, and paying attention to previous case data to implement region-specific precautions. The procedure of ophthalmological emergency and outpatient management should also be optimized, and mental health should be emphasized during this pandemic.

Development of a Gene Risk Signature for Patients of Pancreatic Cancer

Background. Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods. Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result. A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion. This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis.

HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk

Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment (TME) which are closely associated with the tumor malignant progression. However, the regulatory mechanisms by which TAMs influence the progression of triple-negative breast cancer (TNBC) remain unclear. Here, we report that hepatic leukemia factor (HLF) acts as a novel oncoprotein in TNBC. We found that HLF was regulated by transforming growth factor-beta1 (TGF-β1) that is secreted by TAMs. Then, HLF transactivated gamma-glutamyltransferase 1 (GGT1) to promote the ferroptosis resistance, thus driving TNBC cell proliferation, metastasis and cisplatin resistance. Reciprocally, IL-6 produced by TNBC cells activated the JAK2/STAT3 axis to induce TGF-β1 secretion by TAMs, thus constituted a feed-forward circuit. The accuracy of TNBC patient prognosis could be improved by employing a combination of HLF and GGT1 values. Thus, our findings document that the interactive dialogue between TNBC cells and TAMs promotes sustained activation of HLF in tumor cells through the IL-6-TGF-β1 axis. Subsequently, HLF promotes the ferroptosis resistance in TNBC cells via GGT1 and ultimately facilitates the malignant tumor progression. Our study provides a potential target for the treatment of TNBC.

Role and Involvement of TENM4 and miR-708 in Breast Cancer Development and Therapy

Teneurin 4 (TENM4) is a transmembrane protein that is codified by the ODZ4 gene and is involved in nervous system development, neurite outgrowth, and neuronal differentiation. In line with its involvement in the nervous system, TENM4 has also been implicated in several mental disorders such as bipolar disorder, schizophrenia, and autism. TENM4 mutations and rearrangements have recently been identified in a number of tumors. This, combined with impaired expression in tumors, suggests that it may potentially be involved in tumorigenesis. Most of the TENM4 mutations that are observed in tumors occur in breast cancer, in which TENM4 plays a role in cells’ migration and stemness. However, the functional role that TENM4 plays in breast cancer still needs to be better evaluated, and further studies are required to better understand the involvement of TENM4 in breast cancer progression. Herein, we review the currently available data for TENM4′s role in breast cancer and propose its use as both a novel target with which to ameliorate patient prognosis and as a potential biomarker. Moreover, we also report data on the tumorigenic role of miR-708 deregulation and the possible use of this miRNA as a novel therapeutic molecule, as miR-708 is spliced out from TENM4 mRNA.

Based on Bioinformatics Studies on the Effect of a lpha1H on Key Genes, Pathways in Bladder Cancer and lncRNA on Patient Prognosis

Objective: To analyze the differential genes, lncRNA, signaling pathway and patient prognosis of bladder cancer after alpha1H treatment.Methods: Sequencing data GSE172112 for patients in clinical trials with a new bladder cancer drug were downloaded from the GEO database, The bladder cancer tissues using the new drug alpha1H (alpha1-oleate) and placebo were analyzed in the R language, The differentially expressed genes were selected; Differential genes were analyzed for KEGG pathway enrichment using the DAVID database, To explore the effect of a lpha1H treatment on pathways in patients with bladder cancer; at the same time, lncRNA expression data from the Bladder Cancer (BLCA) dataset were also downloaded through the TCGA database, First, screening for differential lncRNA expression, The screening results were then analyzed by univariate Cox regression to initially screen for lncRNA associated with prognosis, The key lncRNA affecting the prognosis were further screened out, The prognostic model was also constructed using multivariate Cox regression analysis. Results: There yielded 394 significantly upregulated genes and 385 significantly downregulated genes in bladder cancer tissue after a lpha1H treatment. Through gene signaling pathway enrichment analysis, the upregulated genes were mainly enriched in the signaling pathways regulating the pluripotent line of stem cell cells, the TGF-signaling pathways, and the cell cycle. The downregulated genes were mainly enriched in the MAPK signaling pathway, phagosomes, and the TNF signaling pathway. After a lpha1H treatment, of 119 differentially expressed lncRNA, from the lnc2cancer database, two genes were found to be potentially associated with bladder cancer prognosis, and the final analysis confirmed the key lncRNA affecting prognosis. The results of survival analysis showed that high expression of LINC00152 unfavorable unfavorable patient prognosis and the new drug alpha1H reduces LINC00152 favors patient prognosis. Conclusion: Alpha1H can cure bladder cancer by regulating hallmark signaling, TGF-beta signaling, and LINC00152.

SORT1/LAMP2-mediated Extracellular Vesicle Secretion and Cell Adhesion Are Linked to Lenalidomide Resistance in Multiple Myeloma

Multiple myeloma (MM) is a hematopoietic malignancy whose prognosis has improved with the development of new agents such as lenalidomide over the last decade. However, long-term exposure to drugs induces the acquisition of resistance by MM cells and leads to treatment failure and poor prognosis. Here, we show the molecular and cellular mechanisms of lenalidomide resistance in MM. In a comparison between lenalidomide-resistant cell lines and the parental cell lines, the EV (Extracellular versicles) secretion and adherence abilities were significantly elevated in the resistant cells. Whole-transcriptome analysis revealed that the SORT1 and LAMP2 genes were key regulators of EV secretion. Silencing of these genes caused decreased EV secretion and loss of cell adhesion in the resistant cells, resulting in increased sensitivity to lenalidomide. Analysis of publicly available transcriptome data confirmed the relationship between genes related to EV secretion and cell adhesion and patient prognosis. Together, our findings reveal a novel mechanism of lenalidomide resistance in MM mediated by EV secretion and cell adhesion via SORT1 and LAMP2.