Pan-cancer analysis of CREB3L1 as biomarker in the prediction of prognosis and immunotherapeutic efficacy.

Background: CAMP response element binding protein 3-like 1 (CREB3L1) has been indicated as a critical biomarker and can modulate multifaced behaviors of tumor cells in diverse cancers. However, a systematic assessment of CREB3L1 in pan-cancer is of absence, and the predictive value of CREB3L1 in cancer prognosis, the tumor immune microenvironment and the efficacy of immunotherapy remains unexplored. Methods: CREB3L1 expression in 33 different cancer types was investigated using RNAseq data from The Cancer Genome Atlas (TCGA) database. The characteristics of CREB3L1 alternations were illustrated in cBioPortal database. The prognostic and clinicopathological value of CREB3L1 was analyzed through clinical data downloaded from the TCGA database. The potential role of CREB3L1 in the tumor immune microenvironment was illustrated by utilizing CIBERSORT and ESTIMATE algorithms, and TISIDB online database. The associations between CREB3L1 expression and tumor mutation burden (TMB), and microsatellite instability (MSI) were assessed by spearman's rank correlation coefficient. Furthermore, Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential biological functions and downstream pathways of CREB3L1 in different human cancers. The correlations of CREB3L1 expression with PD-1/PD-L1 inhibitors efficacy and drug sensitivity were also investigated. Results: The expression of CREB3L1 was abnormally high or low in several different cancer types, and was also strictly associated with the prognosis of cancer patients. CREB3L1 expression levels have a strong relationship with infiltrating immune cells, including regulatory T cells, CD8+ T cells, macrophages, B naïve cells, dendritic cells and mast cells. CREB3L1 expression was also correlated with the expression of multiple immune-related biomolecules, TMB, and MSI in several cancers. Moreover, CREB3L1 had promising applications in predicting the immunotherapeutic benefits and drug sensitivity in cancer management. Conclusions: Our results highlight the value of CREB3L1 as a predictive biomarker for the prognosis and immunotherapy efficacy in multiple cancers, and CREB3L1 seems to play key roles in the tumor immune microenvironment, suggesting the role of CREB3L1 as a promising biomarker for predicting the prognosis and immune-related signatures in diverse cancers.

Low dose aspirin associated with greater bone mineral density in older adults.

The use of low-dose aspirin in older adults is increasing as is the prevalence of osteoporosis. Aspirin has been shown in numerous studies to affect bone metabolism. However, there is no clear link between low-dose aspirin use and bone mineral density (BMD). This study examined differences in bone mineral density between low-dose aspirin users and non-aspirin users in adults aged 50-80 years. We conducted a cross-sectional study of 15,560 participants who participated in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. We used a multivariate logistic regression model to evaluate the relationship between low-dose aspirin and femoral neck BMD, femoral total BMD, intertrochanteric BMD, and the first lumbar vertebra BMD (L1 BMD) in patients aged 50 to 80 years. A total of 1208 (Group 1: femoral neck BMD, total femur BMD, and intertrochanter BMD) and 1228 (Group 2: L1 BMD) adults were included in this study. In both group 1 and group 2, BMD was higher in the low-dose aspirin group than in the non-aspirin group (Total femur BMD ß = 0.019, 95% CI 0.004-0.034; Femoral neck BMD ß = 0.017, 95% CI 0.002-0.032; Intertrochanter BMD ß = 0.025, 95% CI 0.007-0.043; L1 BMD ß = 0.026, 95% CI 0.006-0.046). In subgroup analyses stratified by gender, this positive association existed in both gender after adjusting for confounders. On subgroup analyses stratified by age, this positive association existed in three different age groups after adjusting for confounders. To test whether the effect of low-dose aspirin on BMD was affected by gender and age, the interaction P value was greater than 0.05. These findings from a human study looking into the relationship between low-dose aspirin use and BMD suggest that regular low-dose aspirin may be associated with a higher BMD. The association between low-dose aspirin and BMD did not differ by age group or gender.

Combined analysis of expression, prognosis and immune infiltration of GINS family genes in human sarcoma.

OBJECTIVE: This study was undertaken to explore the expression and prognostic value of GINS family in human sarcoma, as well as the association between the expression levels of the GINS family and sarcoma immune infiltration. RESULTS: We discovered that the mRNA expression levels of GINS1, GINS2, GINS3, and GINS4 were all higher in the majority of tumor tissues than in normal samples, of course, including sarcoma. Through the CCLE, all the four members expression were observed in high levels in sarcoma cell lines. In Gene Expression Profiling Analysis (GEPIA) and Kaplan-Meier Plotter, our results indicated that the poor overall survival (OS), disease-free survival (DFS) and relapse free survival (RFS) were tightly associated with the increased expression of GINS genes. In TIMER database, we found that highly expressed GINS was significantly correlated with the low infiltration level of CD4+ T cell and macrophage. CONCLUSIONS: The four GINS family members were all the prognostic biomarkers for the prognosis of human sarcoma and can reduce the level of immune cell infiltration in the sarcoma microenvironment. METHODS: In terms of the expression levels of mRNA for GINS family members, a particular contrast in various cancers, especially human sarcoma, was conducted through ONCOMINE and GEPIA and CCLE databases. Kaplan-Meier Plotter was used to identify the prognostic value of GINS family in sarcoma. The relationship between the expression level of GINS and the infiltration of immune cells was analyzed in TIMER database.

Integrative analysis of expression, prognostic significance and immune infiltration of RFC family genes in human sarcoma.

OBJECTIVE: To reveal the expression and prognostic value of replication factor C family genes (RFCs) in patients with sarcoma. RESULTS: The results showed that the mRNA expression levels of RFC2, RFC3, RFC4, and RFC5 were increased in sarcoma tissues. In addition, Cancer Cell Line Encyclopedia (CCLE) dataset analysis indicated that RFC1, RFC2, RFC3, RFC4, and RFC5 were elevated expressed in sarcoma cell lines. Moreover, Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier Plotter showed that highly expressed RFC2-5 were associated with poor overall survival (OS) or relapse-free survival (RFS) in sarcoma patients. The results of the Tumor Immune Estimation Resource (TIMER) database indicated that the expression of RFCs was negatively correlated with the infiltration of CD4+ T cells and macrophages. CONCLUSIONS: There were significant differences in the expression of RFCs between normal tissue and sarcoma tissue, and RFC2, RFC3, RFC4, and RFC5 might be promising prognostic biomarkers for sarcoma. METHODS: The expression of RFCs was analyzed using the ONCOMINE dataset and GEPIA dataset. CCLE dataset was used to assess the expression of RFCs in the cancer cell line. The prognostic value of RFCs was evaluated by GEPIA and Kaplan-Meier analysis. Furthermore, the association between RFCs and their co-expressed genes were explored via ONCOMINE and GEPIA datasets. We used the TIMER dataset to analyze the immune cell infiltration of RFCs in sarcoma.

Meta-analysis of colistin for the treatment of Acinetobacter baumannii infection.

Multidrug resistant among Acinetobacter baumannii infection is associated with a high mortality rate and limits the therapeutic options. The aim of this study was to assess the safety and efficacy of colistin monotherapy vs. other single antibiotic therapy AND colistin-based combination therapy (with other antibiotics) vs. colistin alone for the treatment of Acinetobacter baumannii infection. Online electronic database were searched for studies evaluating colistin with or without other antibiotics in treatment of patients with drug-resistant Acinetobacter baumannii infection. Totally, twelve studies met the inclusion criteria. For colistin-based combination therapy, six articles including 668 patients were included. Our results showed that the overall clinical response did not differ significantly between colistin-based combination therapy and monotherapy (OR = 1.37, 95% CI = 0.86-2.19, P = 0.18). This insignificance was also detected in ICU mortality, length of stay and nephrotoxicity (P > 0.05). However, the colistin-based combination therapy was shown increasing the microbiological response (OR = 2.14, 95% CI = 1.48-3.07, P < 0.0001). For colistin monotherapy, six studies involving 491 patients were analyzed. The results were in concordance with the findings of the colistin-based combination therapy group. Our results suggest that colistin may be a promising therapy as safe and efficacious as standard antibiotics for the treatment of drug-resistant Acinetobacter baumannii infection.

Matrine inhibits IL-1ß-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro.

Interleukin (IL)-1ß plays an important role in promoting osteoarthritis (OA) lesions by inducing chondrocytes to secrete matrix metalloproteinases (MMPs), which degrade the extracellular matrix and facilitate chondrocyte apoptosis. Matrine was shown to exert anti-inflammatory effects. However, the role of matrine in OA is still unclear. Therefore, in this study, we investigated the effects of matrine on the expression of MMPs in IL-1ß-treated human chondrocytes and the underlying mechanism. The cell viability of chondrocytes was detected by MTT assay. The cell apoptosis of chondrocytes was measured by flow cytometric analysis. The protein production of MMPs was determined by ELISA. The protein expression of phosphorylation of mitogen-activated protein kinases (MAPKs) and the inhibitor of kappaB alpha (IκBα) was determined by Western blot. Matrine significantly inhibited the IL-1ß-induced apoptosis in chondrocytes. It also significantly inhibited the IL-1ß-induced release of MMP-3 and MMP-13, and increased the production of TIMP-1. Furthermore, matrine inhibits the phosphorylation of p-38, extracellular regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and IκBα degradation induced by IL-1ß in chondrocytes. Taken together, our results show that matrine inhibits IL-1ß-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro. Therefore,-matrine may be beneficial in the treatment of OA.

One-stage surgical management for multilevel tuberculous spondylitis of the upper thoracic region by anterior decompression, strut autografting, posterior instrumentation, and fusion.

STUDY DESIGN: A retrospective clinical study of 1-stage surgical management for multilevel tuberculous spondylitis of the upper thoracic region (MTSUTR). OBJECTIVE: MTSUTR has rarely been documented in the literature. We present a retrospective clinical study of 23 patients with MTSUTR treated by anterior decompression, strut autografting, posterior instrumentation, and fusion. The purpose was to determine the clinical efficacy of such surgical treatment for MTSUTR. SUMMARY OF BACKGROUND DATA: It is considered safe and effective to treat surgically tuberculous spondylitis with local spinal cord compression. Many reports have documented a good clinical efficacy of surgical management for spinal tuberculosis. However, how to deal with MTSUTR is rarely reported in the literature. METHODS: There were 14 men and 9 women, with average age of 35 years. All patients underwent 1 stage anterior debridement, strut autografting, and posterior instrumentation and received combined medication antituberculosis chemotherapy for 12 to 24 months (average 18 mo). The following data were followed up for an average period of 42 months (24 to 60 mo) in these patients: deformity angle, neurologic function, and spinal bony fusion. RESULTS: The average preoperative deformity angle was 44 degrees, correcting to 20-degree postoperatively and 24 degrees at final follow up. In the series, 19 patients with preoperative neurologic deficit restored by 1.3 grades according to Frankel. All patients got bony spinal fusion within 6 months postoperatively. There was no recurrent tuberculous infection. CONCLUSIONS: Single-stage anterior debridement, strut autografting, posterior instrumentation, and fusion proved safe and effective for MTSUTR, which can achieve goals of complete spinal cord decompression and good deformity correction.