A risk model constructed using 14 N6-methyladenosine-related lncRNAs as a new prognostic marker that correlates with the immunomodulatory effect and drug sensitivity in colorectal cancer.

Background: Colorectal cancer (CRC) remains the most common gastrointestinal malignancy. Despite multimodal therapy, its mortality is high due to recurrence and metastasis. This study developed and verified a risk model consisting of 14 N6-methyladenosine (m6A) long noncoding RNAs (lncRNAs) to assess the prognosis of patients with CRC and investigated its relevance to immune regulation and drug sensitivity. Methods: The gene expression profiles and clinical data of 446 patients with CRC were retrieved from The Cancer Genome Atlas (TCGA). 14 lncRNAs were screened using the Gene Co-expression Network (corFilter =0.5, P<0.001), and univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct the optimal risk model. The predictive performance and clinical applicability of the model were next verified. In addition, we performed Gene Ontology (GO) enrichment analysis to identify potential biological functions and detected the difference in tumor mutational burden (TMB), immune function, and sensitivity to immunotherapy and other drugs between the high- and low-risk groups to evaluate the application of the constructed risk model in depth. Results: The model was found to be an appropriate marker for predicting the prognosis of patients with CRC, independent of other clinical features, and demonstrated good precision and broad clinical applicability. It correlated with pathways in the development of cancer and immune-related functions, and patients in the high-risk group had higher tumor immune dysfunction and escape (TIDE) scores. Furthermore, we found significant differences in the overall survival (OS) between patients in the high- and low-tumor mutation burden (TMB) groups, which may work in conjunction with the constructed model to better predict patients' prognosis. Finally, we identified 12 drugs, including A-443654 and sorafenib, with lower half maximal inhibitory concentration (IC50) values in the high-risk group. Conversely, 21 drugs, including gemcitabine and rapamycin, had lower IC50 values in the low-risk group. Conclusions: We constructed a risk model based on 14 m6A-related lncRNAs that could predict the prognosis of patients with CRC and provided additional therapeutic ideas for their treatment. These findings may additionally serve as a foundation for further studies on regulating CRC via m6A-related lncRNAs.

Identification and validation of novel prognostic biomarkers and therapeutic targets for non-small cell lung cancer.

Background: Despite the significant survival benefits of anti-PD-1/PD-L1 immunotherapy, non-small cell lung cancer (NSCLC) remains one of the most common tumors and major causes of cancer-related deaths worldwide. Thus, there is an urgent need to identify new therapeutic targets for this refractory disease. Methods: In this study, microarray datasets GSE27262, GSE75037, GSE102287, and GSE21933 were integrated by Venn diagram. We performed functional clustering and pathway enrichment analyses using R. Through the STRING database and Cytoscape, we conducted protein-protein interaction (PPI) network analysis and identified the key genes, which were verified by the GEPIA2 and UALCAN portal. Validation of actin-binding protein anillin (ANLN) was performed by quantitative real-time polymerase chain reaction and Western blotting. Additionally, Kaplan-Meier methods were used to compute the survival analyses. Results: In total, 126 differentially expressed genes were identified, which were enriched in mitotic nuclear division, mitotic cell cycle G2/M transition, vasculogenesis, spindle, and peroxisome proliferator-activated receptor signaling pathway. 12 central node genes were identified in the PPI network complex. The survival analysis revealed that high transcriptional levels were associated with inferior survival in NSCLC patients. The clinical implication of ANLN was further explored; its protein expression showed a gradually increasing trend from grade I to III. Conclusion: These Key genes may be involved in the carcinogenesis and progression of NSCLC, which may serve as useful targets for NSCLC diagnosis and treatment.

Acupuncture for neuropathic pain: A meta-analysis of randomized control trials.

Background: Neuropathic pain (NP) is expected to increase due to the high risk of global population aging. Acupuncture has a definite clinical effect on NP. Therefore, a systematic review and meta-analysis were conducted to evaluate the effect on pain intensity and safety of acupuncture in patients with NP. Methods: An encompassing search of specific authoritative databases in English, from their inception to 2022, was performed. The databases were as follows: Scopus, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations, and Daily. All the randomized controlled trials regarding the acupuncture treatment of NP will be included. Methodological quality assessment of the included trials was assessed based on the risk of bias from the Cochrane handbook. A meta-analysis was performed for the main outcomes. In addition, sensitivity analysis, subgroup analysis, and funnel plot were also carried out. Results: A total of 16 studies with 1,021 patients with NP were evaluated in a systematic review. According to the results of the overall meta-analysis in eight RCTs with 338 participants, the acupuncture group was better than the control group in improving changes in pain intensity (SMD -0.59, 95% CI: -0.95 to -0.23, P = 0.001). In subgroup analysis, five trials indicated that acupuncture was more effective in improving changes in pain intensity than sham acupuncture (SMD -0.54, 95% CI: -0.95 to -0.13, P = 0.01), two trials evaluated the effect on changes in pain intensity in the comparison of acupuncture and conventional treatments, no significant difference existed (SMD -0.61, 95% CI: -1.83 to 0.61, P = 0.33), and one trial compared acupuncture with blank control evaluating the effect of changes in pain intensity with a significant difference. Eleven studies mentioned the safety conditions and acupuncture-induced AEs were mild and reversible. Both the sensitivity analysis and funnel plot analysis showed that the meta-analysis was stable and irreversible without publication bias. The GRADE was rated as "very low." Conclusion: The acupuncture group had higher effectiveness than sham intervention or blank control for changes in pain intensity, but there is no significant difference between acupuncture and conventional treatments in treating NP. The acupuncture-induced adverse events were mild and reversible. However, the interpretation of our results should be performed cautiously due to the low methodological quality of selected publications. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022306461.

Dietary supplements and herbal medicine for COVID-19: A systematic review of randomized control trials.

BACKGROUND: The world is currently struggling with the Coronavirus disease 2019 (COVID-19) pandemic. Dietary supplements (DSs) and herbal medicine provide a potentially convenient and accessible method for its recovery, but direct evidence is limited. OBJECTIVE: This study aims to investigate the effectiveness of DSs and herbs in patients with COVID-19. METHODS: A systematic literature search was conducted in multiple electronic English and Chinese databases. Randomized controlled trials (RCTs) involving DSs or herbal medicine interventions on patients with COVID-19 from November 2019 to February 2021 were included. Data was extracted, summarized and critically examined. RESULTS: Out of 9402 records identified in the initial search, twelve RCTs were included in this review. Risk of bias of these RCTs was deemed high. Most of the trials were of low methodologic quality. Nine studies showed herbal supplements were beneficial to the recovery of COVID-19 patients; zinc sulfate could shorten the duration of loss of smell but not total recovery from COVID-19. No severe adverse events were reported. CONCLUSION: Herbal supplements may help patients with COVID-19, zinc sulfate is likely to shorten the duration of olfactory dysfunction. DS therapy and herbal medicine appear to be safe and effective adjuvant therapies for patients with COVID-19. These results must be interpreted with caution due to the overall low quality of the included trials. More well-designed RCTs are needed in the future.

Sex-related differences in the efficacy of immune checkpoint inhibitors in malignancy: a systematic review and meta-analysis.

Although disease susceptibility is known to differ between men and women, it is controversial whether the efficacy of immune checkpoint inhibitors for malignancies also differs between the sexes. We conducted a meta-analysis to explore the impact of sex on immune checkpoint inhibitor treatment outcomes. We searched PubMed, Embase and the Cochrane Library databases from inception to October 1, 2020 for randomized controlled trials of immune checkpoint inhibitors with hazard ratios (HRs) stratified by sex. We calculated the pooled HRs for men and women using the ln(HR), and assessed the heterogeneity between the two estimates through an interaction test. In total, 22,268 patients from 39 randomized controlled trials were included. Immune checkpoint inhibitors yielded better overall survival than conventional agents in both men (HR: 0.75, 95% confidence interval [CI]: 0.71-0.80) and women (HR: 0.77, 95% CI: 0.70-0.85). Progression-free survival benefits were also observed in both men (HR: 0.64, 95% CI: 0.58-0.70) and women (HR: 0.67, 95% CI: 0.58-0.77) treated with immune checkpoint inhibitors. No sex differences in the response to immune checkpoint inhibitors were found when overall survival and progression-free survival were used as the endpoints.

Immune checkpoint inhibitors for the management of advanced non-small-cell lung carcinoma: a meta-analysis.

This study is a meta-analysis assessing the safety and efficacy of programmed cell death-1/cell death-ligand 1 (PD-1/PD-L1) inhibitors in order to improve their efficacy in advanced non-small-cell lung cancer. We retrieved studies of anti-PD-1/PD-L1 therapies for non-small-cell lung cancer from electronic databases; 17 clinical trials were analyzed. The pooled hazard ratios for overall and progression-free survival (PFS), and the odds ratios (ORs) for the objective response rate (ORR) and adverse effects were calculated using Review Manager 5.3. The pooled hazard ratios for overall and PFS were 0.69 and 0.74, respectively, and the pooled OR for the ORR was 1.78, implying a significant improvement in overall survival (OS), PFS, and ORR with administration of PD-1/PD-L1 inhibitors. In subgroup analysis, the ORs of the ORR were 2.48 in PD-L1 positive versus negative tumors, and 0.99 for a high dose of PD-1/PD-L1 inhibitors versus a low dose. The ORs for the occurrence of any treatment-related adverse effects and grades 3-5 treatment-related adverse effects were 0.33 and 0.30, respectively, suggesting a good safety profile. PD-1/PD-L1 immunotherapy has superior outcomes in terms of the ORR, OS, and PFS with tolerable adverse effects when compared with chemotherapy.