This study sought to determine whether variables detected on coronary computed tomography angiography (CCTA) would predict plaque progression in non-culprit lesions (NCL).In this single-center trial, we analyzed 103 consecutive patients who were undergoing CCTA and percutaneous coronary intervention (PCI) for culprit lesions. Follow-up CCTA was scheduled 12 months after the PCI, and all patients were followed for 3 years after their second CCTA examination. High-risk plaque features and epicardial adipose tissue (EAT) volume were assessed by CCTA. Each NCL stenosis grade was compared visually between two CCTA scans to detect plaque progression, and patients were stratified into two groups based on this. Logistic regression analysis was used to evaluate the factors that were independently associated with plaque progression in NCLs. Time-to-event curves were compared using the log-rank statistic.Overall, 34 of 103 patients exhibited NCL plaque progression (33%). Logistic regression analyses showed that the NCL progression was associated with a history of ST-elevated myocardial infarction (odds ratio [OR] = 5.855, 95% confidence interval [CI] = 1.391-24.635, p = 0.016), follow-up low-density lipoprotein cholesterol level (OR = 6.832, 95% CI = 2.103-22.200, p = 0.001), baseline low-attenuation plaque (OR = 7.311, 95% CI = 1.242-43.028, p = 0.028) and EAT (OR = 1.015, 95% CI = 1.000-1.029, p = 0.044). Following the second CCTA examination, major adverse cardiac events (MACEs) were observed in 12 patients, and NCL plaque progression was significantly associated with future MACEs (log rank p = 0.006).Noninvasive assessment of NCLs by CCTA has potential prognostic value.
Human decidual natural killer (dNK) cells are a unique type of tissue-resident NK cells at the maternal-fetal interface. dNK cells are likely to have pivotal roles during pregnancy, including in maternal-fetal immune tolerance, trophoblast invasion, and fetal development. However, detailed insights into these cells are still lacking. In this study, we performed metabolomic and proteomic analyses on human NK cells derived from decidua and peripheral blood. We found that 77 metabolites were significantly changed in dNK cells. Notably, compared to peripheral blood NK (pNK) cells, 29 metabolites involved in glycerophospholipid and glutathione metabolism were significantly decreased in dNK cells. Moreover, we found that 394 proteins were differentially expressed in dNK cells. Pathway analyses and network enrichment analyses identified 110 differentially expressed proteins involved in focal adhesion, cytoskeleton remodeling, oxidoreductase activity, and fatty acid metabolism in dNK cells. The integrated proteomic and metabolomic analyses revealed significant downregulation in glutathione metabolism in dNK cells compared to pNK cells. Our data indicate that human dNK cells have unique metabolism and protein-expression features, likely regulating their function in pregnancy and immunity.
A dysregulated immune microenvironment at the maternal-fetal interface in early pregnancy may lead to early pregnancy loss, fetal growth restriction, and preeclampsia. However, major questions about how epigenetic modifications regulate the immune microenvironment during the decidualization process and embryo implantation remain unanswered. DNA methylation, the main epigenetic mechanism involved in the endometrial cycle, is crucial for specific transcriptional networks associated with endometrial stromal cell (ESC) proliferation, hormone response, decidualization, and embryo implantation. Ten-eleven translocation (TET) enzymes, responsible for catalyzing the conversion of 5-methylcytosine to 5-hydroxymethylcyosine, 5-formylytosine, and 5-carboxylcyosine to achieve the DNA demethylation process, appear to play a critical role in decidualization and embryo implantation. Here, we provide a comprehensive view of their structural similarities and the common mechanism of regulation in the microenvironment at the maternal-fetal interface during decidualization and early pregnancy. We also discuss their physiological role in the decidual immune microenvironment. Finally, we propose a key hypothesis regarding TET enzymes at the maternal-fetal interface between decidual immune cells and ESCs. Future work is needed to elucidate their functional role and examine therapeutic strategies targeting these enzymes in pregnancy-related disease preclinical models, which would be of great value for future implications in disease diagnosis or treatment.
Objective: Laryngopharyngeal Reflux Disease (LPRD) is prevalent and has a range of symptoms. However, diagnosing LPRD is difficult because of the lack of specific symptoms or clinical gold standard. An objective and reliable test, which does not rely on a perfect clinical gold standard, is required in clinical practice. Methods: 60 normal volunteers and 74 confirmed Laryngopharyngeal Reflux (LPR) patients were labelled based on the combined consideration of the reflux symptom index, reflux finding score, 24h oropharyngeal pH monitoring and results of anti-reflux treatment. 72 candidate features were extracted from pH recordings and the most efficient feature combination was detected using a stepwise wrapper method. The labelled data were combined with 1552 unlabelled data for feature selection and model training using semi-supervised learning. A latent class model method was used to assess the proposed model based on 64 additional validation data and an imperfect clinical reference test. Results: A new score (named W score), which significantly improved the sensitivity of the LPRD test (82.67% vs. 24.09%) and has a relatively high specificity (80.19%), was proposed. W score concurs with the complicated clinical test. Conclusion: W score which significantly improves LPRD diagnostic efficiency, can aid the clinical diagnosis of LPRD. W score provides an objective, efficient, and reliable indicator for the application of anti-reflux treatment in clinical practice. Significance: More LPRD patients can benefit from anti-reflux treatment in clinical practice and fewer patients may suffer from, for example, the side effects of unnecessary long-term Proton Pump Inhibitors (PPI) treatments.
Progression and chemoresistance of acute myeloid leukemia (AML) contribute to most of the treatment failure. Notch pathway has been proven to be involved in many biological processes and diseases, especially AML. In this study, we aimed to explore genes correlated with Notch1 pathway in AML and determine their roles in the regulation of AML progression and chemoresistance.TCGA database was used to explore Notch1 associated genes. Kaplan-Meier survival analysis was performed to evaluate the prognostic significance of genes. Quantitative RT-PCR (qRT-PCR) and Western blot were performed to examine the expression of genes. The expression of PRKD2 was up-regulated or knocked down in AML cell lines by lentivirus or siRNAs. CCK-8 and flow cytometry were used to analyze the effect of PRKD2 on cell proliferation and chemoresistance.Based on TCGA database, PRKD2 was found to be positively correlated with Notch1 expression, cytogenetic risk status and poorer prognosis in AML. Moreover, the expression level of PRKD2 was higher in AML chemo-resistant cells than in chemo-sensitive cells. Functionally, knockdown of PRKD2-induced apoptosis and increased chemosensitivity of AML cells. PRKD2 overexpression promoted proliferation and chemoresistance of AML cells. Furthermore, we found PRKD2 could regulate Notch1 pathway. Besides, high PRKD2 expression was correlated with higher risk group of AML patients which indicated that PRKD2 was an independent prognostic marker for AML.Taken together, our results showed that PRKD2 could promote the proliferation and chemoresistance of AML cells by regulating Notch1 pathway. The study broadened our insights into the underlying mechanisms in chemoresistance and proliferation of AML, and provided a new prognostic marker and treatment target for AML.
Objective: To explore the utility of pharyngeal pH monitoring which positive standard is Ryan index in diagnosis of laryngopharyngeal reflux disease. Methods: In a retrospective study, clinical data of 590 patients who had symptoms laryngopharyngeal reflux disease from February 2016 to March 2017 were analyzed. All patients were received electronic laryngoscopy, assessment of reflux symptom index(RSI) and reflux finding score(RFS), and pharyngeal pH monitoring. SPSS 19.0 software was used to analyze the date. Results: There were 94 patients whose Ryan index were positive(15.93%). Among the 94 patients, 70 were positive during upright, 12 during supine and 12 during both upright and supine. There were 40 patients(6.78%)with pH decline events related to symptoms, while those Ryan index were normal. There were 536(90.85%), 417(70.68%), 233(39.49%) and 117(19.83%) patients with pH<6.5, pH<6.0, pH<5.5 and pH<5.0 events respectively. The positive rate of RSI, RFS, RSI and RFS, RSI or RFS were 44.24%, 16.78%, 7.12%, 53.90% respectively. The RFS score in Ryan index positive group was higher than that in Ryan index negative group[(8.2±2.4) vs (4.0±2.9), u=5.424, P<0.05], while the RSI score in Ryan index positive group was not statistically different from that in Ryan index negative group[(11.3±6.2) vs (12.7±5.8), t=1.247, P=0.167]. Conclusions: Pharyngeal pH monitoring is an objective and non-invasive method which can reflect laryngopharyngeal reflux directly. However, with the Ryan index as a criterion for the diagnosis of laryngopharyngeal reflux disease, partial patients may be missed. Further studies are needed to obtain more accurate and objective laryngopharyngeal pH statistical index for diagnosis of laryngopharyngeal reflux disease.目的： 探讨以Ryan指数作为判断标准的咽喉部pH监测(Dx-pH)在咽喉反流性疾病中的应用价值。 方法： 回顾性分析2016年2月至2017年3月在解放军第三六医院耳鼻咽喉头颈外科就诊的有咽喉反流症状的590例患者临床资料。所有患者均行电子喉镜检查，反流症状指数量表(reflux symptom index，RSI)和反流体征评分量表(reflux finding score，RFS)及咽部pH监测。采用SPSS 19.0进行统计学分析。 结果： 所有患者监测过程顺利，患者接受度良好。590例患者中Ryan指数阳性率为15.93%(94/590)，其中直立位阳性70例，平卧位阳性12例，直立位、平卧位均阳性12例。Ryan指数正常、但存在症状相关pH下降事件40例(6.78%)。存在pH<6.5、pH<6.0、pH<5.5及pH<5.0事件的患者分别为536例(90.85%)，417例(70.68%)，233例(39.49%)和117例(19.83%)。单纯RSI评分阳性、单纯RFS评分阳性、RSI且RFS评分阳性、RSI或RFS评分阳性的Ryan指数阳性率分别为44.24%、16.78%、7.12%、53.90%。Ryan指数阳性组患者RFS评分高于Ryan指数阴性组患者[(8.2±2.4)分比(4.0±2.9)分，u＝5.424，P<0.05]。；Ryan指数阳性组患者RSI评分与Ryan指数阴性组患者差异无统计学意义[(11.3±6.2)分比(12.7±5.8)分，t＝1.247，P＝0.167]。 结论： 咽喉部pH监测是直接反映咽喉部反流客观、无创的检测方法，以Ryan指数作为咽喉反流性疾病的判断标准，可能会遗漏部分阳性病例，仍需进一步研究用于诊断咽喉反流性疾病的更准确、客观的咽喉部pH统计学指数。.
Osteosarcoma (OS) is a frequently occurring primary bone tumor, mostly affecting children, adolescents and young adults. Before 1970, surgical resection was the main treatment method for OS, but the clinical results were not promising. Subsequently, the advent of chemotherapy has improved the prognosis of patients with OS. However, there is still a high incidence of metastasis or recurrence, and chemotherapy has several side effects, thus making the 5‑year survival rate markedly low. Recently, chimeric antigen receptor T (CAR‑T) cell therapy represents an alternative immunotherapy approach with significant potential for hematologic malignancies. Nevertheless, the application of CAR‑T cells in the treatment of OS faces numerous challenges. The present review focused on the advances in the development of CAR‑T cells to improve their clinical efficacy, and discussed ways to overcome the difficulties faced by CAR T‑cell therapy for OS.
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