Identification of RNA Methylation-Related lncRNAs Signature for Predicting Hot and Cold Tumors and Prognosis in Colon Cancer.

N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G) are the major forms of RNA methylation modifications, which are closely associated with the development of many tumors. However, the prognostic value of RNA methylation-related long non-coding RNAs (lncRNAs) in colon cancer (CC) has not been defined. This study summarised 50 m6A/m1A/m5C/m7G-related genes and downloaded 41 normal and 471 CC tumor samples with RNA-seq data and clinicopathological information from The Cancer Genome Atlas (TCGA) database. A total of 1057 RNA methylation-related lncRNAs (RMlncRNAs) were identified with Pearson correlation analysis. Twenty-three RMlncRNAs with prognostic values were screened using univariate Cox regression analysis. By consensus clustering analysis, CC patients were classified into two molecular subtypes (Cluster 1 and Cluster 2) with different clinical outcomes and immune microenvironmental infiltration characteristics. Cluster 2 was considered to be the "hot tumor" with a better prognosis, while cluster 1 was regarded as the "cold tumor" with a poorer prognosis. Subsequently, we constructed a seven-lncRNA prognostic signature using the least absolute shrinkage and selection operator (LASSO) Cox regression. In combination with other clinical traits, we found that the RNA methylation-related lncRNA prognostic signature (called the "RMlnc-score") was an independent prognostic factor for patients with colon cancer. In addition, immune infiltration, immunotherapy response analysis, and half-maximum inhibitory concentration (IC50) showed that the low RMlnc-score group was more sensitive to immunotherapy, while the high RMlnc-score group was sensitive to more chemotherapeutic agents. In summary, the RMlnc-score we developed could be used to predict the prognosis, immunotherapy response, and drug sensitivity of CC patients, guiding more accurate, and personalized treatment regimens.

Integrated Analysis of Necroptosis-Related Genes for Prognosis, Immune Microenvironment Infiltration, and Drug Sensitivity in Colon Cancer.

Background: Necroptosis, is intimately linked to tumor development and prognosis and has been considered as a target for anticancer therapy. However, the role of necroptosis-related genes (NRGs) in colon cancer is unclear. Methods: In the present study, we screened 76 NRGs from previous studies and described the landscape of transcriptomic and genetic variation of NRGs in colon cancer (CC) patient samples. Molecular subtypes of necroptosis in colon cancer were identified by clustering analysis, and these molecular subtypes were linked to patient prognosis and TME cell infiltration characteristics. Then, the NRS-score for predicting overall survival (OS) was built based on the TCGA database and validated in the GSE39582 cohort for its predictive power in CC patients. Besides, the ESTIMATE and CIBERSORT algorithms were applied to explore the relationship between NRS-score and tumor immune microenvironment. Results: We identified two molecular subtypes associated with necroptosis in CC, which have diverse prognosis and immune microenvironment characteristics. Based on the differentially expressed genes between the two molecular subtypes, we further developed a necroptosis risk score signature, referred to as NRS-score. High NRS-score was associated with poor prognosis in CC through immunosuppressive microenvironment and immune escape mechanisms. The nomogram based on NRS-score showed excellent ability to predict prognosis. In addition, NRS-score presented a positive correlation with tumor mutational burden (TMB) and immune checkpoint blockade (ICB) expression and was closely correlated with multiple anticancer agent susceptibility. Conclusion: This work revealed a close relationship between necroptosis and the prognosis and immune microenvironment of colon cancer. The NRS-score based on the 8-gene signature may be used to predict the sensitivity of immunotherapy and chemotherapy in colon cancer patients, and provides a foundation for future studies targeting necroptosis and its immune microenvironment.

Preoperative Serum Prealbumin Level and Adverse Prognosis in Patients With Hepatocellular Carcinoma After Hepatectomy: A Meta-Analysis.

BACKGROUND: Prealbumin is a sensitive indicator of liver function and nutritional status. OBJECTIVES: This meta-analysis aimed to examine the association of the serum prealbumin level with the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. METHODS: We comprehensively searched the PubMed, Embase, Wanfang, China Academic Journals (CNKI), and SinoMed databases up to September 1, 2021. Eligible studies should report the association of the serum prealbumin level with prognosis and provide the multivariable-adjusted risk estimates of the outcomes of interest in HCC patients undergoing hepatectomy. RESULTS: A total of 11 studies with 7,442 HCC patients were identified and analyzed. Meta-analysis of a fixed effects model showed that a low serum prealbumin level was associated with poor overall survival [hazard ratio (HR) = 1.54, 95% confidence interval (CI) = 1.42-1.68], recurrence-free survival (HR = 1.34, 95% CI = 1.17-1.52), and a higher risk of postoperative hepatic insufficiency (HR = 2.21; 95% CI = 1.36-3.60) in HCC patients. Sensitivity and subgroup analyses confirmed the robustness of low serum prealbumin in predicting poor overall survival. CONCLUSIONS: This meta-analysis indicated that a low preoperative serum prealbumin level was significantly associated with adverse prognosis in HCC patients undergoing hepatectomy.

[The supernatant of 4T1 breast cancer cell culture increases arginase 1 content in ANA-1 macrophages].

OBJECTIVE: To explore the effect of the supernatant of 4T1 murine breast cancer cell culture on arginase 1 (Arg-1) in ANA-1 macrophages in vitro by simulating the microenvironment of breast cancer. METHODS: The experimental ANA-1 macrophages were treated with the supernatant of 4T1 culture, and meanwhile, the control cells were cultured in the absence of the supernatant. Morphological changes of the ANA-1 macrophages were observed with a light microscope at 6, 8, 10, 24 hours, respectively. Real-time quantitative PCR (qRT-PCR) was performed to detect the levels of inducible nitric oxide synthase (iNOS) and Arg-1 mRNAs. Immunofluorescence and Western blotting were used to determine the levels of iNOS and Arg-1 proteins. RESULTS: The qRT-PCR indicated that the level of iNOS mRNA decreased in the experiment group compared with the control group, while Arg-1 mRNA level significantly increased compared with the control group and it reached a peak at the 8th hour. The immunofluorescence and Western blotting also demonstrated that Arg-1 protein expression was enhanced in the experimental group compared with the control group. However, iNOS protein expression was no significantly different between the experiment group and the control group. CONCLUSION: The supernatant of 4T1 cell culture increases Arg-1 production in ANA-1 macrophages.

Calcium channel blocker use and risk of Parkinson's disease: a meta-analysis.

PURPOSES: Whether calcium channel blocker (CCB) use contributes to a low risk of developing a first time diagnosis of Parkinson's disease (PD) remains controversial. We conducted a meta-analysis to investigate the relationship between CCB use and PD risk. METHODS: Pubmed, EMBASE, China National Knowledge Infrastructure, and WanFang databases were searched for papers through May 2014. Studies investigating the association between CCB use and the risk of first time diagnosis of PD were included. Pooled adjusted risk ratio (RR) and 95% confidence interval (CI) were calculated using a fixed-effect model. RESULTS: Five studies involving 208 248 CCB users were identified. Overall, CCB use was associated with a reduction in PD risk (RR = 0.76, 95%CI = 0.68-0.84) compared with the controls. Subgroup analysis showed that dihydropyridine CCB use reduced by 27% PD risk (RR = 0.73, 95%CI = 0.64-0.83) and non-dihydropyridine CCB use reduced by 30% PD risk (RR = 0.70, 95%CI = 0.50-0.93). CONCLUSIONS: Overall, CCB use as a class is associated with a reduction in PD risk. Both of dihydropyridine and non-dihydropyridine CCB use appear to reduce the risk of developing a first time diagnosis of PD. More well-designed prospective studies are needed to investigate the difference of the subtype of CCB user on PD risk.

Losartan treatment for hypertensive patients with hyperuricaemia in Chinese population: a meta-analysis.

OBJECTIVES: Many studies have compared losartan with other antihypertensive agents in the management of hypertensive patients with hyperuricaemia in China. However, systematic assessment of efficacy and safety between losartan and other antihypertensive agents is still lacking. This meta-analysis sought to evaluate the available randomized controlled trials (RCTs) regarding losartan treatment for hypertensive patients with hyperuricaemia in China. METHODS: Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang database were searched until December 2013. Only RCTs comparing losartan with other antihypertensive agents for the management of hypertensive patients with hyperuricaemia in Chinese patients were included. RESULTS: Thirty-one RCTs with 2754 patients were identified. Losartan reduced serum uric acid levels (weighted mean differences  - 1.57 mg/dl, 95% confidence interval -1.83 to -1.30) compared with other antihypertensive agents. No significant differences in the reduction in SBP or DBP were observed. The incidence of adverse events was comparable between losartan and other agents, so no differences were found in dizziness and headache. Losartan generated a lower incidence than angiotensin-converting enzyme inhibitors of reported dry cough (risk ratio 0.19, 95% confidence interval 0.10-0.36). CONCLUSION: There are no significant differences between losartan and other antihypertensive agents in the reduction of blood pressure. However, losartan is superior to other agents in the reduction of serum uric acid levels; it might be a better choice in hypertensive patients with hyperuricaemia.

Effect of Dahuang zhechong formula on liver fibrosis in patients with chronic hepatitis B: a meta-analysis.

BACKGROUND: Dahuang zhechong formula has been used for the treatment of chronic hepatitis B, but its efficacy on the liver fibrosis is conflicting. We performed a meta-analysis to quantitatively investigate the efficacy of Dahuang zhechong formula as an adjunctive therapy treatment for liver fibrosis in patients with hepatitis B. METHODS: We searched the PubMed, EMBASE, VIP database, China National Knowledge Infrastructure, and Wanfang database through January 2014. Only randomized controlled trials investigating Dahuang zhechong formula as an adjunctive therapy treatment for liver fibrosis in patients with chronic hepatitis B were selected. RESULTS: Seventeen trials involving 1212 patients were included. Dahuang zhechong formula reduced serum hyaluronic acid level (standardized mean difference [SMD]=-1.27; 95% confidence interval [CI]: -1.72 to -0.83), type-III procollagen level (SMD=-1.71; 95%CI: -2.34 to -1.09), type-IV collagen level (SMD=-1.06; 95%CI: -1.41 to -0.70), and laminin level (SMD=-0.75; 95%CI: -0.89 to -0.62). In particular, subgroup analyses showed that patients who did not receive anti-viral agents have achieved a greater reduction in serum fibrosis markers. CONCLUSIONS: Dahuang zhechong formula appears to reduce serum biomarkers of liver fibrosis in patients with chronic hepatitis B. However, robust conclusions cannot be reached due to the methodological flaws of the included trials.