Radiofrequency (RF) treatment is an invasive and promising procedure in the treatment of osteoarthritis (OA). A meta-analysis based on 12 RCT studies was to investigate whether invasive RF treatment is more effective in relieving knee pain and improving knee function. Relevant studies were searched on database of Pubmed, Embase, EBSCO, Cochrane library, Wanfang digital database, VIP database, and CNKI up to January 2018. A total of 841 participants from 12 publications were included. The weighted mean difference (WMD) and the corresponding 95% CIs were used to evaluate the difference in pain scores and OKS/WOMAC scores between RF treatment and control groups. The statistical analysis was performed by Stata 12.0. The pain scores (VAS) in the RF group were lower than those in the conservative treatment group after 1 week (WMD -1.77, 95% CI -2.93 to -0.61, P<0.01), 1 month (WMD -1.40, 95% CI -1.98 to -0.82, P<0.01), and 3 months (WMD -1.32, 95% CI -2.27 to -0.37, P<0.01) of treatment, while there was no significant improvement in knee function. In subgroup analyses by site of radiofrequency, RF mode showed some discrepancies in the WMD of VAS between the treatment and control groups. In addition, subgroup analysis and meta-regression showed that the efficacy of RF treatment for reducing pain is reversely related to female ratio, and we did not find any surgery-related adverse reactions. RF treatment significantly reduces the knee pain, but rarely improves the knee joint function. Radiofrequency ablation has better efficacy than pulsed radiofrequency ablation in reducing pain. Furthermore, subgroup analysis and meta-regression suggested that women are more sensitive to RF treatment than men.

TRPV3 is a temperature-sensitive, nonselective cation channel expressed prominently in skin keratinocytes. TRPV3 plays important roles in hair morphogenesis and maintenance of epidermal barrier function. Gain-of-function mutations of TRPV3 have been found in both humans and rodents and are associated with hair loss, pruritus, and dermatitis. Here, we study the mechanisms of acid regulation of TRPV3 by using site-directed mutagenesis, fluorescent intracellular calcium measurement, and whole-cell patch-clamp recording techniques. We show that, whereas extracellular acid inhibits agonist-induced TRPV3 activation through an aspartate residue (D641) in the selectivity filter, intracellular protons sensitize the channel through cytoplasmic C-terminal glutamate and aspartate residues (E682, E689, and D727). Neutralization of the three C-terminal residues presensitizes the channel to agonist stimulation. Molecular dynamic simulations revealed that charge neutralization of the three C-terminal residues stabilized the sensitized channel conformation and enhanced the probability of α-helix formation in the linker between the S6 transmembrane segment and TRP domain. We conclude that acid inhibits TRPV3 function from the extracellular side but facilitates it from the intracellular side. These novel mechanisms of TRPV3 proton sensing can offer new insights into the role of TRPV3 in the regulation of epidermal barrier permeability and skin disorders under conditions of tissue acidosis.

Background: The effect of imaging selection on endovascular therapy for acute ischemic stroke remains debated. We compared the efficacy and safety of imaging modalities using computed tomography perfusion with using noncontrast computed tomography (NCCT)±computed tomography angiography. Methods: Studies from PubMed, Embase, and Cochrane Library up to March 1, 2024, were analyzed. Sixteen studies (12 199 patients) assessed functional independence (modified Rankin Scale score of 0–2 at 90 days) using odds ratios (ORs). This study was registered with the International Prospective Register of Systematic Reviews (CRD42024519554). Results: No significant differences were observed in functional independence (OR, 1.09 [95% CI, 0.98–1.21]), modified Rankin Scale score of 0 to 1 (OR, 1.07 [95% CI, 0.88–1.29]), 0 to 3 (OR, 1.04 [95% CI, 0.92–1.18]), thrombolysis in cerebral infarction 2b to 3 (OR, 1.08 [95% CI, 0.95–1.22]), symptomatic intracranial hemorrhage (OR, 0.87 [95% CI, 0.74–1.04]), and any intracranial hemorrhage (OR, 0.95 [95% CI, 0.80–1.12]) between the computed tomography perfusion and NCCT group. There was a significantly lower odds of death during follow‐up in the computed tomography perfusion group compared with the NCCT group (OR, 0.78 [95% CI, 0.70–0.88]). Comparison of modified Rankin Scale score of 0 to 2 significantly favored NCCT selection for patients with large cores ( P _interaction =0.05). Risk of bias assessment using the Cochrane risk assessment tool revealed concerns in 1 randomized control trial, while observational and post hoc studies assessed with Risk of Bias in Nonrandomized Studies of Interventions I showed moderate (2 studies), serious (11 studies), and critical (2 studies) risk of bias. Conclusions: These findings indicate that patients undergoing endovascular therapy selected with computed tomography perfusion had a similar functional prognosis compared with those selected with NCCT but had lower odds of death during follow‐up. NCCT‐defined large‐core patients had better functional outcomes.

Glucocorticoid-related genes (GRGs) may facilitate tumor immune escape via tumor microenvironment (TME) modulation, but their causal association with non-small cell lung cancer (NSCLC) remains unclear. Herein, we performed Mendelian randomization analysis based on cis-eQTL data from GTEx and eQTLGen databases, combined with SMR and Bayesian colocalization analyses, to identify GRGs with significant causal links to NSCLC. TCGA transcriptomic data verified the differential expression of core GRGs. Single-cell transcriptomic analysis revealed elevated GRGs cellular module scores in M2 macrophages of NSCLC tissues relative to adjacent normal tissues, while the MuSiC algorithm estimated cell-type abundance in bulk transcriptomic datasets. We further integrated three intersecting genes (MRPS7, IQGAP1, EXOC2), M2 macrophage abundance, clinical parameters and radiomics features (extracted via nnU-Net-based segmentation) to construct a multi-omics Cox prognostic risk model. This model achieved an AUC > 0.9 for 1-year survival prediction in the training cohort and maintained robust performance (AUC 0.7–0.9) for 1–5-year survival in the independent test cohort. NSCLC tissue microarrays combined with cellular functional assays confirmed that MRPS7 not only exhibits aberrant overexpression in both NSCLC tissues and cell lines but also reveals a potential role in promoting the progression of NSCLC. This is the first study to systematically elucidate the potential causal relationship between GRGs and NSCLC risk, which may be mediated by regulating M2 macrophage function, providing novel biomarkers for precise prognosis prediction and uncovering potential mechanisms underlying NSCLC oncogenesis.