Revealing underlying regulatory mechanisms of LINC00313 in Osimertinib-resistant LUAD cells by ceRNA network analysis.

BACKGROUND: Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is the preferred treatment for EGFR-mutated lung cancer. However, acquired resistance inevitably develops. While non-coding RNAs have been implicated in lung cancer through various functions, the molecular mechanisms responsible for osimertinib resistance remain incompletely elucidated. METHODS: RNA-sequencing technology was employed to determine differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) between H1975 and H1975OR cell lines. Starbase 2.0 was utilized to predict DE-lncRNA and DE-mRNA interactions, constructing ceRNA networks. Subsequently, functional and pathway enrichment analysis were performed on target DE-mRNAs to identify pathways associated with osimertinib resistance. Key target DE-mRNAs were then selected as potential risk signatures for lung adenocarcinoma (LUAD) prognostic modeling using multivariate Cox regression analyses. The Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and immunohistochemistry staining were used for result validation. RESULTS: Functional analysis revealed that the identified DE-mRNAs primarily enriched in EGFR-TKI resistance pathways, especially in the PI3K/Akt signaling pathway, where their concerted actions may lead to osimertinib resistance. Specifically, upregulation of LINC00313 enhanced COL1A1 expression by acting as a miR-218-5p sponge, triggering an upstream response that activates the PI3K/Akt pathway, potentially contributing to osimertinib resistance. Furthermore, the expressions of LINC00313 and COL1A1 were validated by qRT-PCR, and the activation of the PI3K/Akt pathway was confirmed by immunohistochemistry staining. CONCLUSIONS: Our results suggest that the LINC00313/miR-218-5p/COL1A1 axis potentially contributes to osimertinib resistance through the PI3K/Akt signaling pathway, providing novel insights into the molecular mechanisms underlying acquired osimertinib resistance in LUAD. Additionally, our study may aid in the identification of potential therapeutic targets for overcoming resistance to osimertinib.

Gastrointestinal disease is an important influencing factor of osteoporosis fracture:a retrospective study in chinese postmenopausal women.

BACKGROUD: The influencing factors of osteoporosis are complex, the incidence of osteoporosis is higher in middle-aged and elderly women, and osteoporotic fractures (OF) can seriously affect quality of life. Currently, the correlation analysis between gastrointestinal diseases and OF focuses more on diseases such as gastric cancer and inflammatory bowel disease (IBD). This study analyzed the risk factors for osteoporosis and osteoporotic fractures in 1567 postmenopausal women in Fuzhou, China. The purpose is to explore the potential influence of gastrointestinal diseases on the occurrence of OF. METHODS: According to inclusion and exclusion criteria, a total of 1567 subjects were included in the analysis of OP risk factors, including 647 in the OP group and 920 in the NOP group. A total of 616 subjects were included in the analysis of correlation between OF and gastrointestinal diseases, including 132 in OF group and 484 in NF group. Statistical analysis shows that age (OR = 1.062, 95% CI = 1.045-1.080), height (OR = 0.089, 95% CI = 0.009-0.857), weight (OR = 0.981,95% CI = 0.967-0.995) and nature of work (P = 0.010) are the main risk factors for osteoporosis in postmenopausal women in southeast China, and gastrointestinal diseases (OR = 1.583, 95% CI = 1.070-2.343) and height (OR = 0.003, 95% CI = 0.000-0.104) are the main risk factors of OF. CONCLUSIONS: The main factors affecting the occurrence of OP in postmenopausal women in southeast China are individual characteristic. Gastrointestinal diseases that do not directly affect BMD increase the risk of OF in osteoporotic patients.

Adverse effects produced by different drugs used in the treatment of Parkinson's disease: A mixed treatment comparison.

OBJECTIVE: This mixed treatment comparison is used to compare the adverse effects of eleven different drugs used to treat Parkinson's disease (PD). The drugs that we compare include the following: ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil, pergolide, and levodopa. METHODS: PubMed, EMBASE, and Cochrane Library were searched from the inception to December 2015. Our analysis combines the evidences of direct comparison and indirect comparison between various literatures. We evaluated the merging odds ratios (OR) value and surface under the cumulative ranking curves (SUCRA) of each of the drugs and used this as a mode of comparison. RESULTS: Twenty-four randomized controlled trials (RCTs) were included in this study. Our results demonstrated that the incidence of adverse reactions of ropinirole, rotigotine, entacapone, and sumanirole were obviously higher in terms of nausea compared to the placebo. Ropinirole produced the highest incidence rates of dyskinesia side effects, whereas pramipexole was significantly higher in terms of patients' hallucination. In addition, the SUCRA values of all the drugs showed that the incidence of adverse reaction of pergolide was relatively high (nausea: 83.5%; hallucination: 79.8%); for dyskinesia and somnolence, the incidence of ropinirole was higher (dyskinesia: 80.5%; somnolence: 69.4%); the incidence of adverse reaction of piribedil was higher on PD in terms of dizziness (67.0%); and the incidence of bromocriptine was relatively high in terms of constipation (62.3%). CONCLUSIONS: This mixed treatment comparison showed that the drugs ropinirole, bromocriptine, and piribedil produced the highest incidence rates of nausea, dyskinesia, hallucination, dizziness, constipation, and somnolence symptoms. Thus, we conclude that as these three drugs produced the most frequent symptoms, they are not recommended for the treatment of patients with Parkinson's disease.