METHODS: Transcriptomic and clinical data pertaining to LUAD were retrieved from open-access databases to establish an association between mRNA expression profiles and the presence of TDP-43. A risk-prognosis model was developed to compare patient survival rates across various groups, and its accuracy was also assessed. Additionally, differences in tumor stemness, mutational profiles, tumor microenvironment (TME) characteristics, immune checkpoints, and immune cell infiltration were analyzed in the different groups. Moreover, the study entailed predicting the potential response to immunotherapy as well as the sensitivity to commonly employed chemotherapeutic agents and targeted drugs for each distinct group.
RESULTS: The TDP-43 Co-expressed Gene Risk Score (TCGRS) model was constructed utilizing four genes: Kinesin Family Member 20A (KIF20A), WD Repeat Domain 4 (WDR4), Proline Rich 11 (PRR11), and Glia Maturation Factor Gamma (GMFG). The value of this model in predicting LUAD patient survival is effectively illustrated by both the Kaplan-Meier (K-M) survival curve and the area under the receiver operating characteristic curve (AUC-ROC). The Gene Set Enrichment Analysis (GSEA) revealed that the high TCGRS group was primarily enriched in biological pathways and functions linked to DNA replication and cell cycle; the low TCGRS group showed primary enrichment in immune-related pathways and functions. The high and low TCGRS groups showed differences in tumor stemness, mutational burden, TME, immune infiltration level, and immune checkpoints. The predictions analysis of immunotherapy indicates that the Tumor Immune Dysfunction and Exclusion (TIDE) score (p
METHODS/DESIGN: The efficacy and safety of JPSS herbal formula cream will be evaluated through a prospective, randomized, placebo-controlled trial conducted in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. NSCLC patients with CRF will be randomized into two groups at a ratio of 1:1. Each group will receive either 15 g of the oral JPSS herbal formula cream or placebo twice a day from day 6 to day 20 during two courses of paclitaxel + platinum/docetaxel + platinum/pemetrexed + platinum (TP/DP/AP) chemotherapy. The primary endpoint is the difference in the degree of fatigue between baseline (the day before the start of the intervention) and day 42, which will be assessed by the Revised Piper Fatigue Scale score. The secondary endpoints are quality of life (measured by the 43-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer C43), Eastern Cooperative Oncology Group Performance Status, and Traditional Chinese Medicine syndrome score. The toxicity of the treatments will also be evaluated at the same time. All outcomes will be measured at baseline, day 6, day 21, and day 42 of the treatment.
DISCUSSION: This randomized trial will investigate the efficacy and safety of JPSS applied for CRF in patients with NSCLC.
TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900023451. Registered on 28 May 2019.
RESULTS: CTNNB1 gene of HEK 293T cells was knocked out by CRISPR-Cas9. This was confirmed by sequencing and western blotting. Methylthiazolyl-tetrazolium bromide assays indicated that deletion of β-catenin significantly weakened adhesion ability and inhibited proliferation rate (P
OBJECTIVE: To evaluate the efficacy of exercise and its potential determinants for pain, function, performance, and quality of life (QoL) in knee and hip osteoarthritis (OA).
METHODS: We searched 9 electronic databases (AMED, CENTRAL, CINAHL, EMBASE, MEDLINE Ovid, PEDro, PubMed, SPORTDiscus and Google Scholar) for reports of randomised controlled trials (RCTs) comparing exercise-only interventions with usual care. The search was performed from inception up to December 2017 with no language restriction. The effect size (ES), with its 95% confidence interval (CI), was calculated on the basis of between-group standardised mean differences. The primary endpoint was at or nearest to 8 weeks. Other outcome time points were grouped into intervals, from<1 month to≥18 months, for time-dependent effects analysis. Potential determinants were explored by subgroup analyses. Level of significance was set at P≤0.10.
RESULTS: Data from 77 RCTs (6472 participants) confirmed statistically significant exercise benefits for pain (ES 0.56, 95% CI 0.44-0.68), function (0.50, 0.38-0.63), performance (0.46, 0.35-0.57), and QoL (0.21, 0.11-0.31) at or nearest to 8 weeks. Across all outcomes, the effects appeared to peak around 2 months and then gradually decreased and became no better than usual care after 9 months. Better pain relief was reported by trials investigating participants who were younger (mean age<60 years), had knee OA, and were not awaiting joint replacement surgery.
CONCLUSIONS: Exercise significantly reduces pain and improves function, performance and QoL in people with knee and hip OA as compared with usual care at 8 weeks. The effects are maximal around 2 months and thereafter slowly diminish, being no better than usual care at 9 to 18 months. Participants with younger age, knee OA and not awaiting joint replacement may benefit more from exercise therapy. These potential determinants, identified by study-level analyses, may have implied ecological bias and need to be confirmed with individual patient data.