The Diagnostic Value of BRAF V600E Gene Detection Combined with DNA Ploidy Analysis in Thyroid Cancer.

BACKGROUND: The thyroid cancer incidence has been experimenting an accelerated growth all over the world. The serine/threonine-protein kinase (BRAF) V600E gene detection or the DNA ploidy analysis has been employed in the identification of thyroid cancer type. This study aimed to evaluate the diagnostic value of the BRAF V600E gene integrated with DNA ploidy analysis in thyroid cancer. METHODS: From August 2022 to May 2023, 400 individuals from the thyroid surgery outpatient department of our hospital were enrolled in this study. The participants were divided into low-risk groups (Ⅰ+Ⅱ+Ⅲ group; n = 200) and high-risk groups (Ⅳ+Ⅴ group; n = 200) based on the Thyroid Imaging Reporting and Data System (TI-RADS). A total of the patients were subjected to the DNA ploidy analysis, the BRAF V600E gene detection, or the combination of both techniques. We evaluated the diagnostic value of the above techniques and considered the postoperative pathology results as gold standard for cancer diagnosis. The negative predictive value (NPV), accuracy, specificity, sensitivity, and positive predictive value (PPV) of TI-RADS, BRAF V600E gene detection, DNA ploidy analysis, and BRAF V600E gene detection joined with DNA ploidy analysis were calculated. RESULTS: Among 400 subjects, 238 presented thyroid cancer and 162 had benign lesions, according to the postoperative pathology results. The obtained sensitivity, specificity, accuracy, PPV, and NPV values of TI-RADS were 55.88%, 58.64%, 57.00%, 66.50%, 47.50%, respectively; of BRAF V600E gene detection were 81.93%, 69.75%, 77.00%, 79.92%, 72.44%, respectively; of DNA ploidy analysis were 83.19%, 72.84%, 79.00%, 81.82%, 74.68%, respectively; of BRAF V600E gene combined with DNA ploidy analysis were 90.34%, 76.54%, 84.75%, 84.98%, 84.35%, respectively. Compared with TI-RADS, the sensitivity, specificity, accuracy, PPV, and NPV values of DNA ploidy analysis, BRAF V600E gene detection, and the conjunction of these last two methods were increased (p < 0.05). The combination of DNA ploidy analysis and BRAF V600E gene detection had the highest values among them all. CONCLUSIONS: BRAF V600E gene detection in conjunction with DNA ploidy analysis showed a better diagnostic value than both methods separately or TI-RADS.

Triptolide ameliorates osteoarthritis by regulating nuclear factor kappa B-mediated inflammatory response.

OBJECTIVES: Osteoarthritis (OA) is a joint degenerative disease that commonly occurs in older people and affect the quality of life. Triptolide (TPL), a compound derived from Tripterygium wilfordii, has been shown to exhibit anti-inflammatory properties. Here, we investigated the therapeutic effect of TPL on the experimental OA as well as the underlying molecular mechanisms. METHODS: OA models were established using monosodium iodoacetate (MIA) or surgery. The arthritis score and paw withdrawal threshold value of knees were used to evaluate the degree of arthritis. The level and expression of proinflammatory cytokines were evaluated by quantitative real-time PCR and ELISA kits. KEY FINDINGS: In surgery and MIA-induced OA rats, TPL alleviated arthritis symptoms and reduced inflammatory cytokine production in serum. In primary chondrocytes, TPL dose-dependently reversed lipopolysaccharide (LPS)-induced cell proliferation. Moreover, LPS-induced cell apoptosis and the expressions of proinflammatory cytokines interleukin-(IL-)6, IL-8, IL-1ß, IL-12, tumour necrosis factor-α (TNF-α) and interferon-gamma (INF-γ) were also attenuated by TPL. Mechanistically, the therapeutic effects of TPL on OA were effective by dampening nuclear factor kappa B (NF-κB) activity leading to reduced proinflammatory cytokines production and inflammatory response. CONCLUSIONS: TPL acts as an effective therapeutic drug for OA by mediating NF-κB signalling, thereby leading to the reduced proinflammatory cytokines production and inflammatory response.

Low dose of indomethacin and Hedgehog signaling inhibitor administration synergistically attenuates cartilage damage in osteoarthritis by controlling chondrocytes pyroptosis.

Blockade of Hedgehog signaling can prevent osteoarthritis (OA) syndromes. However, the amelioration of related inflammation condition is limited. The purpose of this study was to observe the effect of combined use of Hedgehog signaling inhibitor GANT-61 and common clinical anti-inflammatory drug indomethacin on cartilage injury and inflammation in experimental OA mice. We found that GANT-61 and indomethacin synergistically attenuate cartilage damage and serum levels of inflammatory cytokines TNF-α, IL-2 and IL-6 in OA mice. Moreover, in vitro treatment of GANT-61 and indomethacin synergistically reduced the mRNA expression of TNF-α, IL-2 and IL-6 in lipopolysaccharide (LPS)-stimulated C28/I2 chondrocytes. Mechasnistic studies showed that GANT-61 and indomethacin synergistically attenuate the expressions of cell pyroptosis-related genes caspase-1, IL-1ß and IL-18 at mRNA and protein level. To conclude, our study showed that GANT-61 and indomethacin had a synergistically ameliorating effect on osteoarthritis by mediating chondrocytes pyroptosis.