Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

Interaction between ACOT7 and LncRNA NMRAL2P via Methylation Regulates Gastric Cancer Progression.

PURPOSE: Gastric cancer (GC) has a very poor prognosis when diagnosed at a late stage. Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the acyl coenzyme family that catalyzes the hydrolysis of fatty acyl-CoAs into unesterified free fatty acid and coenzyme A. The purpose of this study was to investigate the expression levels of ACOT7 in GC and mechanisms related therewith. MATERIALS AND METHODS: Screening of systematic biology studies revealed ACOT7 as a key gene in GC, as well as involvement of the long non-coding RNA NMRAL2P in ACOT7 expression. In this study, GC tissues and adjacent tissue samples were obtained from 10 GC patients at the Department of Gastrointestinal Surgery. GES1 and SGC-7901 cells were collected and treated to silence ACOT7 and overexpress NMRAL2P. The expressions of ACOT7 and NMRAL2P were detected by real-time quantitative PCR and Western blot. Additionally, cell proliferation, apoptosis, migration, and invasion were examined. RESULTS: ACOT7 was upregulated in gastric tumor tissues and GC cell lines. ACOT7 gene silencing induced a less malignant phenotype and was closely correlated to reduced cell proliferation and migration, altered cell cycle, and increased apoptosis. Furthermore, NMRAL2P was downregulated in tumor tissues and GC cell lines. NMRAL2P overexpression induced a more malignant phenotype and significantly inhibited the expression of ACOT7. Importantly, NMRAL2P indirectly methylated ACOT7 by binding to DNMT3b, thereby suppressing ACOT7 expression. CONCLUSION: NMRAL2P activation suppresses ACOT7 expression in GC. Thus, ACOT7 could be a promising target for the treatment of GC.

Is oral contraceptive use associated with an increased risk of cervical cancer? An evidence-based meta-analysis.

AIM: The purpose of this meta-analysis is to synthesize evidence-based case-control studies to evaluate the association between oral contraceptive (OC) use and the risk of cervical cancer. METHODS: Two reviewers independently selected potentially relevant studies through PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, and the Chongqing VIP databases using the core terms cervical intraepithelial neoplasia/ cervix dysplasia/ cervi* AND oral contraceptive in the article titles, abstracts, and keywords. All data were analyzed using stata 12.0. The heterogeneity was assessed by Q-test and I2 statistic. Forest plot was used to display results graphically. Publication bias was assessed by Begg's test. RESULTS: In total, 16 case-control studies, including 15 619 participants (7433 cases and 8186 controls), met the eligibility criteria. Individuals with OC use were not found to have a risk of cervical cancer (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.90-1.38). In subgroup analyses, no significant associations were found for different durations of OC use (<5 years: OR, 0.84; 95%CI, 0.68-1.04; 5-10 years: OR, 1.06; 95%CI, 0.66-1.71; >10 years: OR, 1.25; 95%CI, 0.76-2.06). Additionally, using OC was not shown to increase the risk of cervical cancer among women with human papillomavirus infections (OR, 1.09; 95%CI, 0.80-1.49). However, an increased risk of cervical cancer was found in Asian populations with OC use. CONCLUSION: The meta-analysis of case-control studies did not show an association between OC use and risk of cervical cancer. However, other necessary prospective cohort studies should be conducted to assess the impact of OC use on cervical cancer risk in the future.

[Mechanism and re-ablation strategy for postablation atrial tachyarrhythmia in atrial fibrillation patients].

OBJECTIVE: To investigate the mechanism and re-ablation strategy of recurrent atrial tachyarrhythmia (ATA) following circumferential ablation of pulmonary veins (PV) in patients with atrial fibrillation (AF). METHODS: Fifteen patients with recurrent ATA following first AF ablation procedure were included in this study. Under CARTO guidance, PVs were remapped and ablated subsequently for relapse of left atrium to PV conduction. The whole atrium was then remapped and individualized ablation was made to eliminate inducible ATA. RESULTS: Left atrium to PV conduction relapses were evidenced in 14 patients. After re-ablation, there were no inducible ATA in 9 patients, inducible left atrial macro-reentry tachycardia in 3 patients and all were terminated by further linear ablation on the roof and left atrial isthmus, inducible atrial focal tachycardia from left atrial isthmus in 1 patient and was eliminated after additional focal ablation, inducible right atrial macro-reentry tachycardia in 2 patients and were eliminated by right isthmus linear ablation. During 1 - 16 (5.5 +/- 4.4) months follow-up, ATA was disappeared in 13 patients and reduced in another 2 patients. CONCLUSIONS: Relapse of left atrium to PV conduction is one of the main mechanisms for postablation ATA in patients with AF. Atrial macro-reentry tachycardia and focal atrial tachycardia were less common mechanisms for postablation ATA. Re-ablation focused on closing the PV gaps and additional individualized focal and lineal ablation strategies were helpful for treating postablation ATA in AF patients.