AIMS:The prognostic value of late gadolinium enhancement (LGE) phenotypes-particularly subendocardial involvement-for sudden cardiac death (SCD) remains unclear in dilated cardiomyopathy (DCM). Whether LGE phenotype integrating pattern and location can improve SCD risk stratification is an unmet need. METHODS AND RESULTS:DCM patients who underwent cardiac MRI were retrospectively enrolled. The endpoint was a composite of SCD and surrogate SCD events. Among 902 patients (mean age 46 ± 14 years, 78.7% men), subendocardium-involved and mid-wall LGE were observed in 129 (14.3%) and 263 (29.1%) patients, predominantly involving the lateral (65.1%) and septal wall (97.7%), respectively. During a median follow-up of 77 months (IQR 40-92 months), 51 (5.7%) patients experienced SCD events. Multivariable analysis identified septal mid-wall LGE (HR 3.59; 95% CI 1.73-7.47; P = 0.001) and lateral subendocardium-involved LGE (HR 3.07; 95% CI 1.39-6.75; P = 0.005) as independent predictors. A three-tier risk stratification model was developed, classifying patients into: lowest risk (neither septal mid-wall nor lateral subendocardium-involved LGE; reference), intermediate risk (either phenotype alone; HR 4.8, 95% CI 2.2-10.46, P < 0.001), and highest risk (both phenotypes; HR 10.71, 95% CI 3.53-32.46, P < 0.001). The model showed the best improvement in model discrimination and reclassification over left ventricular ejection fraction (C-statistic improvement: 0.23; net reclassification improvement = 0.67; integrative discrimination index = 0.27; all P < 0.05). CONCLUSION:SCD was predicted by both lateral subendocardium-involved LGE and septal mid-wall LGE in DCM. The novel SCD risk model integrating these phenotypes demonstrated superior prognostic performance compared with conventional prognosticators.

Objective To evaluate the potential mediating role of left ventricular ejection fraction (LVEF) in the relationship between replacement fibrosis (assessed by late gadolinium enhancement (LGE)) and sudden cardiac death (SCD) post-myocardial infarction (MI) and also to assess this mediation effect in subgroups based on LVEF ≤ 35% and > 35% according to implantable cardioverter-defibrillator (ICD) selection criterion.Methods A retrospective analysis was conducted on 917 post-MI patients (mean age: 56.3±11.0 years, 88.8% male) who underwent cardiac MR from January 2017 to August 2021. The endpoint for SCDs included SCD, aborted SCD and appropriate ICD discharges. The association of LGE with LVEF was quantified using linear regression models. The associations of LGE and LVEF with SCDs were evaluated using competing risk models. Mediation analysis was then used to decompose the total effect of LGE on SCDs into direct and indirect (mediated through LVEF) effects using accelerated failure time models.Results Over a median follow-up of 63.3 (IQR, 43.6 to 76.6) months, 65 patients (7.1%) experienced SCDs. In all patients, LGE was significantly associated with lower LVEF (β=-0.35, p<0.001). Both LGE and LVEF independently predicted SCDs (subdistribution hazard ratio (sHR)=1.06, p<0.001; sHR=0.95, p=0.03, respectively). Mediation analysis showed that LVEF accounted for 19.7% of the total effect of LGE on SCDs (p<0.001). This mediation effect was 40.4% in patients with LVEF > 35% (p = 0.02), while no mediation was observed in patients with LVEF ≤ 35% (p = 0.08).Conclusion LVEF partially mediated the effect of LGE on the SCD, accounting for less than one-fifth of the total effect. LVEF alone inadequately captured the whole SCD risk, irrespective of whether LVEF is greater than 35% or 35% or less.

BACKGROUND:The prognostic value of persistent microvascular obstruction (persistent-MVO) in ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI) remains unclear. OBJECTIVES:To investigate the prognostic value of persistent-MVO in reperfused STEMI. METHODS:Retrospectively analyzed 504 STEMI patients with primary PCI who underwent a follow-up cardiac magnetic resonance at ≥60 days after PCI. Persistent-MVO was defined as the presence of MVO on late gadolinium enhancement (LGE) imaging, which served as the study baseline. The endpoint was composite events of heart failure (HF), including HF-related death, heart transplantation, left ventricular assist device implantation, and HF hospitalization. Competing risk analysis was performed to address the possible influences of competing events. RESULTS:Persistent-MVO was detected in 44 of 504 patients (8.7%). These patients demonstrated lower left ventricular ejection fraction, larger end-diastolic volume index, and larger LGE extent (all P < 0.05), compared with those without. During a median follow-up of 64.5 months (IQR: 45.0-79.4), 91 of 504 patients (18.1%) experienced the endpoint. Adding persistent-MVO to a model with NYHA functional class, left ventricular ejection fraction, and LGE extent improved model discrimination (C-index: from 0.78 [95% CI: 0.73-0.83] to 0.82 [95% CI: 0.77-0.86], P = 0.01), model fit (-2 log-likelihood: from 996.7 to 984.8, P < 0.001), and risk reclassification (continuous net reclassification improvement: 8.56% [95% CI: 2.60%-16.23%], P < 0.01), with decision curve analysis confirming net clinical benefit at 5 years. CONCLUSIONS:Persistent-MVO was observed in 8.7% of STEMI patients at least 60 days after PCI and provided incremental value beyond established risk markers for predicting HF-related events.

Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic malignancy closely associated with genetic predisposition and environmental factors, such as Epstein-Barr virus (EBV) infection. Zinc finger protein 618 (ZNF618), a member of the zinc finger protein family, plays a critical role in transcriptional regulation, yet its specific function in NPC remains unclear. This study employed a multi-omics approach to systematically analyze the expression profile, clinical significance, and transcriptional regulatory mechanisms of ZNF618 in NPC. Our results demonstrated that ZNF618 was significantly overexpressed at both mRNA and protein levels in NPC tissues (p < 0.05), and its high expression was strongly associated with poor patient prognosis (p < 0.05). Gene set enrichment analysis (GSEA) revealed that ZNF618 was positively correlated with pathways related to head and neck squamous cell carcinoma, while negatively associated with immune-related pathways, such as cytokine–cytokine receptor interaction. Chromatin immunoprecipitation sequencing (ChIP-seq), combined with single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), identified ENAH as a potential target gene of ZNF618, and their co-expression patterns were further validated in NPC. AlphaFold3 simulation analysis revealed interaction between the ZNF618 protein and the promoter region of the ENAH gene. This study suggests that ZNF618 may promote NPC progression and metastasis by transcriptionally activating target genes like ENAH. The overexpression of ZNF618 could serve as a potential diagnostic and prognostic biomarker for NPC. These findings provide novel insights into the molecular mechanisms of NPC and lay the foundation for developing targeted therapeutic strategies. Further studies are warranted to validate the functional mechanisms and clinical applications of ZNF618.

BACKGROUND:The prognostic value of serial myocardial fibrosis assessments in hypertrophic cardiomyopathy (HCM) remains to be elucidated. OBJECTIVES:The study aims to investigate late gadolinium enhancement (LGE) progression via follow-up cardiac magnetic resonance (CMR) in HCM patients and its prognostic value. METHODS:Retrospective analysis included 313 HCM patients with 2 CMR studies (between 2010 and 2019). LGE mass progression (ΔLGE mass/y) was defined as the increase in grams of enhanced myocardium divided by interval scan years. The primary endpoint included all-cause mortality, heart transplantation, aborted sudden cardiac death, unscheduled hospitalization for heart failure, and stroke. The secondary endpoint included all-cause mortality, aborted sudden cardiac death, and heart transplantation. Maximally selected rank statistical analysis was conducted to identify the optimal cutoff for ΔLGE mass/y. RESULTS:LGE mass progressed from a median of 2.9 g at the first CMR study to 8.3 g at the second CMR study (median scan interval 4.2 years). During a median follow-up period of 3.4 years after the second CMR study, 69 patients reached the primary endpoint, 17 of whom reached the secondary endpoint. For the primary and secondary endpoints, the optimal cutoffs for ΔLGE mass/y were >1.50 and 3.75 g/y, respectively. Multivariable Cox regression analysis showed that ΔLGE mass/y >1.50 g/year was an independent predictor of the primary endpoint (HR: 2.22 [95% CI: 1.13-4.34]; P = 0.02). The addition of ΔLGE mass/y to the baseline model improved the discrimination (C-statistic = 0.81 vs 0.84) and risk reclassification (net reclassification improvement = 0.27, integrated discrimination improvement = 0.02; P < 0.001 for both). External validation in 6 multicenter data sets confirmed the prognostic value of ΔLGE mass/y. CONCLUSIONS:In HCM patients, myocardial fibrosis increased over time. Serial assessments of myocardial fibrosis on CMR may improve risk stratification and clinical decision-making.

Background:This study aimed to compare the dosimetric characteristics of lattice radiotherapy across different linear accelerator platforms (Versa HD, Halcyon, and NeuRT Aurora) and to evaluate the feasibility of its clinical application. Methods:This study included ten patients with bulky tumors who were eligible for spatially fractionated radiotherapy, including five pelvic cases and five abdominal cases. For each patient, high-dose vertices were contoured within the gross tumor volume using a standardized method, followed by three independently designed treatment plans on the Versa HD, Halcyon, and NeuRT Aurora platforms. The prescribed dose was 2400 cGy in three fractions. Dosimetric evaluation of the target volume included vertex coverage, maximum dose, and the peak-to-valley dose ratio. In addition, a vertex-specific dose analysis was performed to quantify the number of vertices with a D95 of less than 2400 cGy. For organs at risk, the following dosimetric parameters were evaluated: the mean dose to the intra-lattice margin volume, the maximum dose to tissues located more than 2 cm from the vertices, and standard dosimetric parameters for the spinal cord, small bowel, colon, liver, stomach, lungs, and kidneys. Results:All plans demonstrated the characteristic dosimetric features of lattice radiotherapy by establishing alternating high-dose peaks and low-dose valleys within the target volume, while achieving effective protection of surrounding normal tissues without compromising target coverage. Among the three platforms, NeuRT Aurora demonstrated superior performance in dose gradient control and normal tissue protection. The mean peak-to-valley ratios were 6.4, 6.9, and 8.9 for the Versa HD, Halcyon, and NeuRT Aurora platforms, respectively. The maximum dose to tissues located more than 2 cm from the vertices was significantly lower in the NeuRT Aurora plans (1158.6 cGy) than in the Versa HD plans (1280.6 cGy) and Halcyon plans (1257.8 cGy). Consistent with this trend, the NeuRT Aurora plans were also associated with a lower mean dose to the intra-lattice margin volume (792.4 cGy) than the Versa HD (831.4 cGy) and Halcyon (845.7 cGy) plans. For all specific organs at risk, the evaluated dosimetric parameters remained within clinical tolerance limits across the three treatment platforms. Conclusions:This study systematically evaluated lattice radiotherapy plans across three accelerator platforms. Although differences were observed in peak-to-valley ratios and organ-at-risk sparing, all plans met clinical requirements, confirming the overall feasibility of each platform.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare histologic subtype of gastric cancer with distinct pathological features and poor prognosis. Surgery and chemotherapy remain the primary treatment modalities, but outcomes are generally unsatisfactory. Radiotherapy can enhance tumor immunogenicity by releasing tumor antigens, thereby promoting antitumor immune responses and potentiating the efficacy of immune checkpoint inhibitors. We report a case of advanced HAS that progressed after first-line treatment with chemotherapy, immunotherapy, and targeted therapy. The patient subsequently received a combination of radiotherapy, programmed cell death protein 1 (PD-1) blockade, and granulocyte-macrophage colony-stimulating factor (GM-CSF)—termed PRaG therapy. The tumor demonstrated significant shrinkage following PRaG treatment and ultimately achieved pathologic complete response (pCR), with no serious adverse events aside from mild abdominal pain (NRS score 2). This case suggests that PRaG therapy may represent a promising therapeutic approach for patients with metastatic HAS.

BACKGROUND:Left ventricular (LV)-global longitudinal strain (GLS) assessed by cardiac magnetic resonance (CMR) feature tracking is an emerging marker for predicting adverse outcomes in hypertrophic cardiomyopathy (HCM), but its incremental prognostic value and mechanistic role in sudden cardiac death (SCD) risk stratification remain unclear. OBJECTIVES:The study sought to evaluate whether LV-GLS adds prognostic value beyond current ESC (European Society of Cardiology) and ACC (American College of Cardiology)/AHA (American Heart Association) SCD risk models, and mediates the relationship between myocardial abnormalities and SCD risk in HCM. METHODS:The authors retrospectively analyzed 2,009 patients with HCM (mean age: 50 ± 14 years, 70% men) who underwent CMR between 2010 and 2017. LV-GLS was quantified using cine CMR feature tracking. The primary endpoint included SCD and aborted SCD. Prognostic performance was assessed using time-dependent receiver-operating characteristic analysis and competing risk regression. Mediation analysis was used to investigate how LV-GLS mediated associations between myocardial hypertrophy, fibrosis, and SCD. RESULTS:Over a median follow-up of 88.2 months, 85 (4.2%) patients experienced SCD events. These patients had significantly lower absolute LV-GLS values (9.0% ± 3.6% vs 11.1% ± 3.6%; P < 0.001). In competing-risk regression, LV-GLS independently predicted SCD after adjustment for ESC (subdistribution HR [sHR]: 1.12 per 1% decrease [95% CI: 1.06-1.22]; P < 0.001) and ACC/AHA risk factors (sHR: 1.09 [95% CI: 1.02-1.18]; P = 0.016). Adding LV-GLS improved the 5-year predictive accuracy of both ESC and ACC/AHA models (AUC from 0.72 to 0.77 and from 0.71 to 0.76, respectively). Absolute LV-GLS with a cutoff of 9.23% further stratified risk in patient subgroups with either class II or class III implantable cardioverter-defibrillator indications (all log-rank P < 0.001). Mediation analysis showed LV-GLS partially mediated the effect of maximum wall thickness and extent of fibrosis on SCD (proportion-mediated: 17.5% and 23.1%, respectively; both P < 0.001). CONCLUSIONS:In patients with HCM, CMR-derived LV-GLS is an incremental predictor of SCD beyond current guideline-based risk models and partially mediates the association between myocardial abnormalities and SCD.

BackgroundThe cervical node with necrosis (CNN) is an important poor prognostic factor for nasopharyngeal carcinoma (NPC) patients. The tumor microenvironment of the CNN has severely insufficient blood perfusion, thus leading to hypoxia and reducing the effect of radiotherapy (RT) and chemotherapy. By using contrast-enhanced ultrasound (CEUS) as a monitoring method, we conducted this study to assess whether antiangiogenic therapy (AT) with recombinant human endostatin (RHES) may improve blood perfusion of the CNN.Materials and methodsFifteen NPC patients with CNN were enrolled and underwent CEUS the day before and day 5 after AT with RHES initiation, respectively. By analyzing the variations of CEUS parameters of CNN, such as peak intensity (PI), time to peak (TTP), and mean transit time (MTT) at different time points, we evaluate the impact of AT with RHES on blood perfusion of CNN.ResultsThe PI of day 5 after AT was significantly enhanced compared to the PI of the day before AT [−44.94 ± 4.72 (dB) vs. −50.33 ± 6.85 (dB), p < 0.001]. The TTP of day 5 after AT became dramatically shorter than the TTP of the day before AT [19.48 ± 3.63 (s) vs. 24.19 ± 6.93 (s), p = 0.031]. The MTT of day 5 after AT became obviously shorter than the MTT of the day before AT [28.08 ± 3.03 (s) vs. 33.76 ± 6.20 (s), p = 0.001].ConclusionThese results revealed that the blood volume and the blood flow velocity in the microvessels of the CNN increased after AT, indicating that AT with RHES may improve blood perfusion in the CNN of NPC, thus providing valuable insights for the clinical application of AT combined with RT and/or chemotherapy in NPC patients with CNN. Moreover, CEUS as a noninvasive and real-time monitoring method may be suitable for clinically evaluating tumor blood perfusion changes.

To assess the left ventricular remodeling index (LVRI) for predicting ventricular tachyarrhythmia (VTA) in patients with dilated cardiomyopathy (DCM) with left ventricular ejection fraction (LVEF) < 35

BACKGROUND:Immunotherapy has emerged as a promising avenue for malignant tumors treatment, but methods to validate its in vivo antitumor activity remain limited. Granzyme B, a key mediator of immune-mediated cell death, is a potential biomarker for assessing immunotherapy efficacy. This study aimed to develop a radiotracer with high sensitivity and specificity for in vivo imaging of granzyme B. METHODS:10 granzyme B targeting inhibitors were synthesized and evaluated to improve binding affinity. The most promising compound was conjugated with 1,4,7-triazacyclononane-N,N',N"-triacetic acid chelator and radiolabeled with Al18F to generate radiotracer 18F-G1. Its imaging and pharmacokinetic properties were compared with those of the recently developed radiotracer 68Ga-grazytracer. 18F-G1 was applied to assess T cell-mediated and natural killer (NK) cell-mediated antitumor immunity. In addition, the cyclic guanosine monophosphate AMP synthase-stimulator of interferon genes (cGAS-STING) pathway-targeted therapies were also quantitatively evaluated using 18F-G1. RESULTS:18F-G1 was produced with high radiochemical purity of >98% through a simple radiolabeling procedure. It displayed a 4.2-fold improvement in granzyme B binding affinity compared with grazytracer. In the anti-programmed cell death protein-1 antibody-treated MC38 tumor model, 18F-G1 outperformed 68Ga-grazytracer with significantly higher tumor uptake (2.1-fold increase in maximum tumor uptake) and superior tumor-to-muscle contrast (7.46 vs 2.33). For NK cell-based therapy, 18F-G1 positron emission tomography (PET)/CT successfully monitored granzyme B release following NK-92MI cell injection, with peak signals observed 24 hours postinjection. 18F-G1 PET/CT detected robust immune activation in SR-717-treated tumors compared with other cGAS-STING pathway-targeted drug treatments, which correlated with the highest CD8+ T cell infiltration, granzyme B expression level and tumor growth inhibition. CONCLUSIONS:18F-G1 is an effective granzyme B imaging radiotracer. Its superior imaging properties make it a promising tool for non-invasively evaluating the therapeutic efficacy of various types of immunotherapies with high sensitivity.

Background:Recently, late gadolinium enhancement (LGE) has been identified as an important risk factor in pediatric hypertrophic cardiomyopathy (HCM). However, its prognostic significance in pediatric HCM remains to be fully validated, particularly in Asian population. This study aims to assess the prognostic value of LGE and explore its incremental utility in predicting sudden cardiac death (SCD) in pediatric HCM using data from a Chinese cohort. Methods:231 primary HCM patients ≤18 years of age with cardiac magnetic resonance (CMR) were retrospectively and consecutively enrolled in a single center. The composite outcomes included SCD or equivalent events and heart failure-related events. Findings:Of 231 patients (median age 15, IQR: 12-16), LGE was present in 195 (84.4%) with a median LGE extent of 4.7% (IQR: 2.0%-9.2%). During a median follow-up of 62 months (IQR: 39-85), 26 (11.3%) patients reached composite outcomes, and 13 (5.6%) patients experienced SCD events. Kaplan-Meier analysis showed a significantly increased risk of composite outcomes (log-rank P < 0.001) and SCD (log-rank P < 0.001) in the group with LGE extent ≥5%. In multivariable Cox analysis adjusted by clinical and imaging factors, LGE extent was independently associated with composite outcomes (adjusted HR: 1.15; P < 0.001) and SCD (adjusted HR: 1.11; P = 0.009). For SCD events, the addition of LGE extent could improve the model performance of HCM Risk-Kids model (C-statistics: 0.65 versus 0.79, P = 0.015) and PRIMaCY model (C-statistics: 0.62 versus 0.82, P = 0.002), respectively. Interpretation:In Chinese pediatric HCM, LGE serves as a risk factor in predicting adverse outcomes and may enhance SCD risk stratification strategies. Funding:This study was funded by the National Key Research and Development Program of China (2021YFF0501400 and 2021YFF0501404), the Key Project of the National Natural Science Foundation of China (82430066), and the Yunnan Province Science and Technology Platform and Talent Project (202305AF150033).

Anthracycline-induced cardiotoxicity (AIC), whose major manifestation is diffuse myocardial fibrosis, is an important clinical problem in cancer therapy. Therefore, early identification and treatment are clinically important. This study aims to explore the feasibility of using 68 Ga-labelled fibroblast activation protein (FAP) inhibitor ([68 Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for the early identification of the fibrotic process and guidance of antifibrosis therapy in AIC. An AIC rat model was induced by the intravascular administration of doxorubicin (DOX) once per week for 1, 2, 3 and 6 weeks (2.5 mg/kg/injection, groups 1–4), whereas intravascular saline was administered to control rats. Experimental and control groups (n = 4) underwent [68 Ga]Ga-FAPI PET/CT following disease induction. Groups 5 and 6 received DOX injections for 3 and 6 weeks, treated with angiotensin-converting enzyme (ACE) inhibitor starting at 3 weeks, treated with enalapril (20 mg/kg, gastric gavage) daily and underwent echocardiography and [68 Ga]Ga-FAPI PET/CT at 3 weeks after treatment. Rat hearts were subjected to haematoxylin and eosin staining, FAP immunohistochemistry, Sirius red staining and Masson’s trichrome staining to investigate the pathological changes and deposition of collagen fibres. Rat blood was sampled weekly for the enzyme-linked immunosorbent assay of various markers of myocardial injury, such as plasma cardiac troponin I, B-type natriuretic peptide and angiotensin II. [68 Ga]Ga-FAPI-04 uptake by the heart was significantly higher in the cardiotoxicity group than in the control group at weeks 3 (SUVmax: 1.21 ± 0.23 vs 0.67 ± 0.01, P < 0.05) and 6 (SUVmax: 1.48 ± 0.28 vs 0.67 ± 0.08, P < 0.001), whereas left ventricle ejection fraction (LVEF) did not significantly differ between normal and AIC rats at week 3. FAP+ expression began to increase starting at week 3, before irreversible fibrotic changes were detected, until week 6. After 3 weeks of enalapril treatment, [68 Ga]Ga-FAPI-04 accumulation decreased in groups 5 and 6 (SUVmax decreased from 1.21 ± 0.23 to 0.77 ± 0.08 and 1.48 ± 0.28 to 1.09 ± 1.06, P < 0.05). Cardiac function was preserved (LVEF was 75.7

This study aimed to evaluate the prognostic value of left atrial (LA) strain in patients with apical hypertrophic cardiomyopathy (ApHCM), as assessed by cardiac magnetic resonance (CMR) imaging. Four hundred and five consecutive patients with ApHCM who underwent CMR examination were retrospectively included. The study endpoint included all-cause death, heart transplant, aborted sudden cardiac death, hospitalization for heart failure, stroke, and new-onset atrial fibrillation (AF). After a median follow-up of 97 months, 75 patients (18.5

6002 Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) has long been regarded as standard treatment for LA-NPC. However, approximately 30% of patients still fail to obtain a satisfactory effect. Endostar (Rh-endostatin), an anti-angiogenesis inhibitor, is well-tolerated and has been reported as a promising complement to CCRT. This trial aimed to evaluate the efficacy and safety of adding Endostar to CCRT for LA-NPC. Methods: In this prospective, randomized phase III study, patients with LA-NPC (stage III-IVb, 7th edition) were enrolled at 6 centers in China, and randomly assigned (1:1) to receive Endostar plus CCRT (CCRT+E group, n=150) or CCRT alone (CCRT group, n=150). Endostar (7.5 mg/m2/day, days 1-10, 15 days/cycle) was given continuously intravenously for 5 cycles (3 concurrent from 5 days before radiotherapy, and 2 adjuvant from the first day after the completion of radiotherapy). The primary endpoint was the progress-free survival (PFS) rate. The secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local-regional relapse-free survival (LRRFS), the rate of complete response (CR) at 3 months after RT, and safety. Results: Between November 2016 and July 2020, 300 patients with LA-NPC were randomized (CCRT+E group, 150; CCRT group, 150). As of the data cutoff (December 2023), the median follow-up was 66 months. Intention-to-treat analysis showed that patients in the CCRT+E group achieved better CR rate at 3 months after RT (90.0% vs 80.7%, P=0.022). The 3-year PFS was 84.8% in the CCRT+E group, and 75.1% in the CCRT group (HR, 0.544; 95% CI, 0.336-0.879; Plog-rank=0.011). The 3-year OS was 89.2% vs. 85.3% (HR, 0.595; 95% CI, 0.361-0.982; Plog-rank=0.039). The 3-year DMFS was 89.7% vs. 80.5% (HR, 0.468; 95% CI, 0.266-0.821; Plog-rank=0.007). The 3-year LRRFS was 91.5% vs. 90.8% (HR, 0.808; 95% CI, 0.407-1.604; Plog-rank=0.541). Patients in the CCRT+E group and in the CCRT group had similar Grade 3-4 acute and late toxicity profile (61.7% vs. 65.3%, p=0.519 and 8.0% vs.7.3%, p=0.815). Conclusions: The addition of Endostar to standard CCRT significantly improved the 3-year PFS of LA-NPC patients with good safety profile. Clinical trial information: NCT02907710 .

This study aimed to evaluate whether granzyme B (GzmB)-targeted positron emission tomography (PET) imaging agent (68 Ga-grazytracer) can characterize cardiac inflammation and remodeling in myocardial infarction (MI). Rats with MI were subjected to GzmB-targeted PET/CT on post-operative days 1, 3, 6, 14, and 28. Autoradiography, Masson staining, immunohistochemistry, and ELISA were performed to verify the inflammatory response and remodeling after MI in vitro. Rats were treated with GzmB inhibitor Z-IETD-FMK to improve cardiac remodeling. Cardiac function tests were performed by echocardiography at 6 weeks after MI. The highest uptake of 68 Ga-grazytracer was observed on day 3 after MI compared with the values obtained on the other days (0.294 ± 0.03

目的 探究汉黄芩素对鼻咽癌细胞C666-1、HK-1增殖、迁移和侵袭能力的影响.方法 采用CCK8实验明确汉黄芩素对鼻咽癌细胞C666-1、HK-1的活性抑制作用,并计算IC50;采用平板集落形成实验明确汉黄芩素对鼻咽癌细胞C666-1增殖和独立生存能力的影响;采用划痕实验和Transwell迁移实验研究汉黄芩素对鼻咽癌细胞迁移能力的影响;最后采用Transwell侵袭实验研究汉黄芩素对鼻咽癌细胞侵袭能力的影响.结果 CCK8实验结果显示,汉黄芩素对C666-1和HK-1细胞的活力均表现出明显的抑制作用,随药物浓度增加,抑制效果明显增强;同一药物浓度下,药物作用48 h的抑制效果高于24 h,抑制效果表现为剂量时间依赖性;汉黄芩素作用于C666-1细胞24 h的IC50值为37.15 μmol/L、48 h为20.75 μmol/L;汉黄芩素作用于HK-1细胞24 h的1C50值为29.09 p.mol/L、48 h为20.46 μmol/L.平板集落实验结果显示,汉黄芩素干预后,鼻咽癌细胞C666-1细胞形成肉眼可见集落的数目更少,体积更小.划痕实验和Transwell迁移实验显示,C666-1及HK-1细胞的迁移能力明显受到抑制,且药物浓度越高,抑制作用越强.Transwell侵袭实验显示,汉黄芩素干预后,穿过基质胶后迁移至下室的细胞数目明显减少.结论 汉黄芩素能抑制鼻咽癌细胞的活性、增殖、迁移以及侵袭的能力.

Despite the use of cardiovascular magnetic resonance (CMR) feature tracking (FT) imaging to detect myocardial deformation, the optimal strain index in dilated cardiomyopathy (DCM) is unclear. This study aimed to determine whether atrial and biventricular strains can provide the greatest or joint incremental prognostic value in patients with DCM over a long follow-up period. Four hundred-twelve DCM patients were included retrospectively. Comprehensive clinical evaluation and imaging investigations were obtained, including measurements of CMR-FT derived left atrial (LA) reservoir, conduit, booster strain (εs, εe, εa); left ventricular (LV) and right ventricular (RV) global longitudinal, radial, circumferential strain (GLS, GRS, GCS). All patients were followed up for major adverse cardiac events (MACE) including all-cause mortality, heart transplantation, and implantable cardioverter defibrillator discharge. The predictors of MACE were examined with univariable and multivariable Cox regression analysis. Subsequently, nested Cox regression models were built to evaluate the incremental prognostic value of strain parameters. The incremental predictive power of strain parameters was assessed by Omnibus tests, and the model performance and discrimination were evaluated by Harrell C-index and integrated discrimination improvement (IDI) analysis. Patient survival was illustrated by Kaplan–Meier curves and differences were evaluated by log-rank test. During a median follow-up of 5.0 years, MACE were identified in 149 (36

The high mortality of breast cancer is closely related to lymph node (LN) metastasis. Sentinel LNs (SLNs) are the first station where tumor cells metastasize through the lymphatic system. As such, achieving precise diagnosis of the early metastatic status of SLNs during surgery is of paramount importance for precision therapy of breast cancer. While invasive SLNs biopsy is the gold standard for evaluating the status of SLNs, its use is often time-consuming and may increase the risk of operation. It is still challenging to develop a means for rapid SLN metastasis diagnosis. Herein, NaGdF4:5%Nd@NaLuF4 rare earth nanoparticles (Gd:Nd-RENPs) with near-infrared-II (NIR-II) fluorescence and magnetic resonance imaging (MRI) properties were fabricated. With the nanoprobe, metastatic SLNs and lymph vessels (LVs) rapidly brighten and can be observed by the NIR-II imaging system, which is totally different from normal LNs and LVs. The remarkable contrast observed via NIR-II imaging serves to swiftly delineate metastatic SLNs from normal ones, subsequently guiding precise surgical resection of metastatic LNs in just 10 minutes. Furthermore, the consistency between the results obtained via MRI and NIR-II imaging further validates the dependability of this nanoprobe as a diagnostic tool for metastatic SLNs. Additionally, the Gd:Nd-RENPs exhibited good biocompatibility in vitro and in vivo. In this study, we demonstrated the advantages and prospects of NIR-II imaging for intraoperative early SLN metastasis assessment and shed light on the potential of the dual-modal Gd:Nd-RENPs as a nanoprobe.

Abstract Backgrand : Laryngeal squamous cell carcinoma (LSCC), which arises from the laryngeal mucosa, is the main type of laryngeal cancer. An influence of Zinc finger protein 2 (ZIC2) expression on the occurrence and progression of LSCC has not been established. We aim to identify the clinical importance of ZIC2 expression in LSCC and to explore its latent potential mechanisms. Methods: In this study, we studied the relationship between protein and mRNA expression of ZIC2 in LSCC and clinical pathological features and prognoses via mining the high-throughput sequencing data from multiple databases and to use immunohistochemistry (IHC) and integrated analysis. Meanwhile the downstream targets of ZIC2 transcription factor were also predicted with ChlP-seq data. The KEGG, GO and PPI analysis were applied to identified the potential mechanism of ZIC2 in LSCC. After constructing ZIC2 stable expression cells, we attempt to disclose an association between ZIC2 and cell cycle and apoptosis with RT-qPCR and Western blot methods. Cell cycle was detected by flow cytometry. Results: A higher ZIC2 expression in LSCC were found in both protein and mRNA level by integrated analysis (standard mean difference, SMD=1.76 (95% CI, 1.34–2.18)). The IHC staining of ZIC2 protein is nuclear in LSCC. Kinesin family member 14 (KIF14) was explored as the potential downstream target gene of ZIC2. ZIC2 has a binding peak before the transcription start site of KIF14 and their expression were positively correlated with each other. The expression of KIF14 was elevated after overexpressing ZIC2. The KEGG analysis revealed that ZIC2 may involve LSCC by cell cycle. Cell cycle testing revealed that in ZIC2 knockdown cells, G1 phase increased while S phase was decreased. After knockdown ZIC2 expression, the expression of P21 was elevated, Bax protein was increased while Bcl2 decreased. The analysis of the summary receiver operating characteristic (sROC) demonstrated that ZIC2 may have potential to become a diagnostic marker for LSCC. Conclusions: In conclusion, up-regulation of ZIC2 may contribute to LSCC pathogenesis in cell cycle pathway and it may target KIF14 in LSCC, but these need further research in the future.