Expression and clinical significance of Capase3 and C-IAP1/2 in ectopic endometrium of patients with endometriosis.

To analyze the expression of capase3 and C-IAP1/2 in endometriosis and their relationship with clinical practice. Ectopic and eutopic endometrial tissues were collected from women with endometriosis, and the control tissues were obtained from regular patients without endometriosis. The expression level of capase3 and C-IAP1/2 was detected by immunohistochemistry; in addition, the relationship between C-IAP1/2 expression and the clinical stage of endometriosis was analyzed. The expression of Caspase-3 in ectopic and eutopic endometrium was significantly lower than that in the control group (P < 0.005). The expression of C-IAP1/2 in ectopic and situ endometrium was significantly higher than in the control group (P < 0.005). The expression of C-IAP1/2 in stage III-IV was higher than in stage I-II endometriosis. The positive expression of c-IAP1 protein in ectopic endometrial tissue was negatively correlated with the positive expression of Caspase-3 protein in ectopic endometrial tissue (P<0.001). The low expression of Caspase-3 and the high expression of C-IAP1/2 in the ectopic endometrium and eutopic endometrial tissues compared with the controls. The results indicated that the apoptotic ability of eutopic and ectopic endometrium is weakened, which is involved in the pathogenesis of endometriosis. It is expected to be a target for the diagnosis and therapy of this disease. At the same time, the expression level of C-IAP1/2 is related to the stage of endometriosis, which can guide clinical treatment.

Primary and Acquired Resistance against Immune Check Inhibitors in Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors have emerged as the treatment landscape of advanced non-small cell lung cancer (NSCLC) in recent years. However, approximately 80% of NSCLC patients do not benefit from ICIs due to primary resistance (no initial response) or acquired resistance (tumor relapse after an initial response). In this review, we highlight the mechanisms of primary and secondary resistance. Furthermore, we provide a future direction of the potential predictive biomarkers and the tumor microenvironmental landscape and suggest treatment strategies to overcome these mechanisms.

Late-term safety and effectiveness of everolimus-eluting stents in chronic total coronary occlusion revascularization: Final 4-year results from the evaluation of the XIENCE coronary stent, Performance, and Technique in Chronic Total Occlusions (EXPERT CTO) multicenter trial.

BACKGROUND: Limited study has detailed the late-term safety and efficacy of chronic total coronary occlusion (CTO) revascularization among multiple centers applying modern techniques and with newer-generation drug-eluting stents. METHODS: Among 20 centers, 222 patients enrolled in the XIENCE coronary stent, performance, and technique (EXPERT) CTO trial underwent CTO percutaneous coronary intervention (PCI) with everolimus-eluting stents (EES). Through planned 4-year follow-up, the primary composite endpoint of major adverse cardiac events (MACE; death, myocardial infarction [MI] and target lesion revascularization) and rates of individual component endpoints and stent thrombosis were determined. RESULTS: Demographic, lesion, and procedural characteristics included prior bypass surgery, 9.9%; diabetes, 40.1%; lesion length, 36.1 ± 18.5 mm; and stent length, 51.7 ± 27.2 mm. By 4 years, MACE rates were 31.6 and 22.4% by the pre-specified ARC and per-protocol definitions, respectively. Clinically-indicated target lesion revascularization at 4 years was 11.3%. In landmark analyses of events beyond the first year of revascularization, the annualized rates of target vessel-related MI and clinically-indicated target lesion revascularization were 0.53 and 1.3%, respectively. Through 4 years, the cumulative definite/probable stent thrombosis rate was 1.7% with no events occurring beyond the initial year of index revascularization. CONCLUSIONS: In a multicenter registration trial representing contemporary technique and EES, these results demonstrate sustained long-term safety and effectiveness of EES in CTO percutaneous revascularization and can be used to inform shared decision making with patients being considered for CTO PCI relative to late safety and vessel patency.

Impaired vasomodulation is associated with reduced neuronal nitric oxide synthase in skeletal muscle of ovariectomized rats.

In exercising skeletal muscle, vasoconstrictor responses to alpha-adrenoceptor activation are attenuated in part by nitric oxide (NO) produced by the neuronal isoform of NO synthase (nNOS), which is expressed constitutively in skeletal muscle cells. In skeletal muscle of pregnant animals, nNOS mRNA is upregulated, suggesting that muscle nNOS expression is modulated by the steroid hormone oestrogen. Whether oestrogen-induced changes in nNOS expression have measurable effects on vasoregulation in skeletal muscle is unknown. In this study, we hypothesized that oestrogen deficiency would reduce muscle nNOS expression, resulting in impaired modulation of sympathetic vasoconstriction in exercising skeletal muscle. Compared to gonadally intact rats, we found that ovariectomized (OVX) rats were characterized by greater sympathetic vasoconstriction in contracting hindlimb and reduced nNOS, but not eNOS, in skeletal muscle. In addition, NOS inhibition resulted in a greater enhancement of sympathetic vasoconstriction in contracting hindlimbs of intact compared to OVX rats. These effects of oestrogen deficiency were prevented by chronic treatment of OVX rats with 17beta-oestradiol, but not with chronic progesterone or acute oestradiol. Further analysis revealed that skeletal muscle nNOS correlated directly with plasma 17beta-oestradiol and inversely with the magnitude of sympathetic vasoconstrictor responses in contracting hindlimbs. These data indicate that NO-dependent attenuation of sympathetic vasoconstriction in contracting skeletal muscle is impaired in oestrogen-deficient female rats, and suggest that this impairment may be mediated by reduced skeletal muscle nNOS expression.