Objectives:We evaluated the clinical significance of unipolar electrogram and bipolar electrogram in guiding radiofrequency ablation for outflow tract ventricular premature contractions(PVC).Methods:Data were collected from 78 patients who underwent successful radiofrequency ablation of PVC.Pre-procedure electrocardiogram showed a LBBB morphology on inferior leads.In the included patients,the right-side ablation was performed at first,and if the ablation failed,the left-side ablation was then performed.According to the location of the successful ablation target,they were divided into unilateral ablation successful group and bilateral ablation successful group.The differences in the earliest bipolar local activation to QRS(LATBi),unipolar-dV/dTmax to QRS(LATUni),and local activation time were compared between the two groups.Furthermore,the electrogram characteristics predicting bilateral ablation were explored.Results:Patients were divided into unilateral ablation group(n=57)and bilateral ablation group(n=21)according to the ablation site.There were statistically significant differences in LATBi(25[21,30]ms vs.14[10,24]ms),LATUni(7[0,17]ms vs.-23[-41,-11]ms),and ΔLATBi-Uni(15[11,25]ms vs.44[25,56]ms)between the unilateral ablation group and the bilateral ablation group(all P<0.05).Multivariate regression analysis suggested that LATBi,LATUni,and ΔLATBi-Uni were independent predictors of the need for bilateral ablation.There was no significant difference between left and right LATBi,LATUni and ΔLATBi-Uni in the bilateral ablation group.LATUni≤-1 was the most accurate parameter for predicting the need for bilateral ablation(AUC=0.941;specificity 80.7%;sensitivity 100%).Conclusions:LATUni≤-1ms is a useful indicator for predicting the need for bilateral PVC ablation in this patient cohort.

Cutaneous melanoma(CM)is a highly malignant tumor caused by malignant proliferation of melanocytes,characterized by distant metastasis and high mortality.Although targeted therapy and immunotherapy have significantly improved the survival rates of advanced CM patients,tumor resistance remains a key barrier to further improving treatment outcomes.In recent years,significant progress has been made in the study of autophagy as a key regulatory cell death mode in the pathogenesis of CM.Autophagy is the main mechanism that mediates the degradation and recycling of various cellular components through lysosomes to maintain the homeostasis of the intracellular environment.A large number of studies have confirmed that the role of autophagy in CM is complex and controversial.In the early stages of CM development,autophagy may inhibit abnormal proliferation of tumor cells by removing damaged cell components.However,as the tumor progresses,autophagy may transform into a role that promotes tumor invasion and metastasis.In advanced CM,the activation of autophagy helps tumor cells survive in stressful environments.In particular,in CM with BRAF(V-Raf murine sarcoma viral oncogene homolog B1)mutations,autophagy activity is often enhanced,weakening the effectiveness of BRAF inhibitor-targeted therapy.This article provides an in-depth analysis of the dual effects of autophagy on the progression of CM and explores the role of autophagy in CM resistance,in order to provide insights for the development of new targeted therapy strategies for CM.

Skin malignancies include non-melanoma skin cancers and melanoma,with high incidence rates that pose a significant burden on public health and healthcare systems.Research in this area is crucial.Ultraviolet radiation(UV)is recognized as the primary risk factor for skin malignancies,with its main carcinogenic mechanism involving UV-induced DNA damage,which leads to the accumulation of mutations in key oncogenes and tumor suppressor genes.This accumulation promotes malignant transformation of related cells,ultimately resulting in the formation of malignant tumors.Understanding the specific processes through which UV-induced DNA damage contributes to the development of skin malignancies is crucial for advancing related research.Therefore,this paper focuses on the mechanisms of UV-induced DNA damage,the repair mechanisms for UV-induced DNA damage,and the relationship between UV-induced DNA damage and the occurrence of the three major types of skin malignancies.

Objective:To assess the long-term risk of relapse in patients with Crohn's disease (CD) who discontinued infliximab (IFX) monoclonal antibody and to identify risk factors associated with relapse.Methods:A single-center retrospective observational study was conducted from February 2006 to October 2016. The study included CD patients who were treated with scheduled IFX infusions at the First Affiliated Hospital of Sun Yat-sen University and assessed in corticosteroid-free clinical remission at the time of withdrawal were included. The primary outcome was clinical relapse. We evaluated the risk of relapse using Kaplan-Meier method. Factors associated with time to relapse was identified using the multiple Cox proportional hazards regression analysis.Results:We included 97 eligible patients, and 75 (77.3%) experienced a relapse after a median follow-up time of 124 months. Among them, 45 patients (46.4%) relapsed within 3 years after IFX withdrawal. The 1-, 2-, 3-, 5-, and 10-year relapse-free survival were 79.4%, 59.8%, 52.6%, 42.0% and 22.6%, respectively. Risk factors for relapse included age ≤ 16 ( HR = 2.62, 95% CI: 1.30-5.31; P = 0.007) and failure to achieve biological remission (CRP > 3 mg/L, HR = 2.37, 95% CI: 1.29-4.36; P = 0.006) at drug withdrawal. Induction with biologics or systemic steroids were both effective (89%-100% relieved) in relapsers. Conclusions:Nearly half of CD patients relapsed within 3 years after discontinuation of IFX treatment. Early age of discontinuation and failure to achieve serum biological remission at the time of discontinuation are independent predictors of clinical relapse.

Skin malignancies include non-melanoma skin cancers and melanoma,with high incidence rates that pose a significant burden on public health and healthcare systems.Research in this area is crucial.Ultraviolet radiation(UV)is recognized as the primary risk factor for skin malignancies,with its main carcinogenic mechanism involving UV-induced DNA damage,which leads to the accumulation of mutations in key oncogenes and tumor suppressor genes.This accumulation promotes malignant transformation of related cells,ultimately resulting in the formation of malignant tumors.Understanding the specific processes through which UV-induced DNA damage contributes to the development of skin malignancies is crucial for advancing related research.Therefore,this paper focuses on the mechanisms of UV-induced DNA damage,the repair mechanisms for UV-induced DNA damage,and the relationship between UV-induced DNA damage and the occurrence of the three major types of skin malignancies.

Cutaneous melanoma(CM)is a highly malignant tumor caused by malignant proliferation of melanocytes,characterized by distant metastasis and high mortality.Although targeted therapy and immunotherapy have significantly improved the survival rates of advanced CM patients,tumor resistance remains a key barrier to further improving treatment outcomes.In recent years,significant progress has been made in the study of autophagy as a key regulatory cell death mode in the pathogenesis of CM.Autophagy is the main mechanism that mediates the degradation and recycling of various cellular components through lysosomes to maintain the homeostasis of the intracellular environment.A large number of studies have confirmed that the role of autophagy in CM is complex and controversial.In the early stages of CM development,autophagy may inhibit abnormal proliferation of tumor cells by removing damaged cell components.However,as the tumor progresses,autophagy may transform into a role that promotes tumor invasion and metastasis.In advanced CM,the activation of autophagy helps tumor cells survive in stressful environments.In particular,in CM with BRAF(V-Raf murine sarcoma viral oncogene homolog B1)mutations,autophagy activity is often enhanced,weakening the effectiveness of BRAF inhibitor-targeted therapy.This article provides an in-depth analysis of the dual effects of autophagy on the progression of CM and explores the role of autophagy in CM resistance,in order to provide insights for the development of new targeted therapy strategies for CM.

In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.

Objective:To investigate the dosimetric impact of dwell position spacing in the design of three-dimensional (3D) interstitial brachytherapy plans for cervical cancer, and to provide a reference for selecting dwell spacing in clinical planning.Methods:A total of 15 patients with cervical cancer who underwent 3D interstitial brachytherapy at Tianjin Medical University Cancer Institute & Hospital between March 2022 and March 2024 were selected using simple random sampling. For each patient, 10 brachytherapy plans were generated with different dwell position spacings set at 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 mm, respectively. Key parameters among different dwell spacings compared included D 90%, V 100%, V 200%, and V 300% for the high-risk clinical target volume (HRCTV); D 90% for the intermediate-risk clinical target volume (IRCTV); D 2 cm3 for organs at risk (OARs) (bladder, small intestine, colon, and rectum); and the total dwell time. Statistical analyses were performed using repeated measurement ANOVA or the Friedman test. Results:Among different dwell spacings, there were no statistically significant differences in HRCTV D 90%, HRCTV V 100%, bladder D 2 cm3, and rectum D 2 cm3 among different dwell spacings ( P=0.075, 0.061, 0.480, 0.639). All plans with dwell spacings ≤ 3 mm met clinical dose requirements. When the dwell spacing was set to 1 mm, HRCTV V 200% and V 300% had the smallest mean values, while IRCTV D 90% and total dwell time had the largest mean values; all differences were statistically significant ( P<0.05). When the dwell spacing was ≥6 mm, an increase in spacing led to a decrease in mean small intestine D 2 cm3, and total dwell time, but an increase in HRCTV V 200% and a decrease in IRCTV D 90%, with statistically significant differences compared to spacings of 1-4 mm ( P<0.05). When the dwell spacing was ≥8 mm, the median colon D 2 cm3 decreased, with statistically significant differences compared to spacings of 1-3 mm ( P<0.05). Conclusions:For 3D interstitial brachytherapy planning in cervical cancer, dwell position spacings ≤ 3 mm can meet clinical dose requirements, with 1 mm providing optimal target coverage. Spacings ≥6 mm / ≥8 mm can reduce radiation dose to the small intestine and colon, respectively, while also shortening dwell time.

Objective:To investigate the impact of imaging anatomical features on the prognosis of middle-aged and elderly patients with anomalous coronary artery originating from the opposite sinus (ACAOS).Methods:This retrospective cohort study enrolled patients aged ≥45 years who were diagnosed with ACAOS by coronary computed tomography angiography (CTA) at the Affiliated Hospital of Xuzhou Medical University between January 1, 2011, and December 31, 2018. Baseline clinical data and coronary CTA images were collected. Anatomic imaging features were extracted, including ACAOS subtype, course of the anomalous vessel, and ostial angle. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, cardiac death, and coronary revascularization. The Maxstat method was used to determine the cut-off values of specific anatomical features for predicting MACE risk. Cox proportional hazards models were employed to analyze the impact of these imaging features on MACE in middle-aged and elderly ACAOS patients.Results:A total of 203 patients were enrolled, aged (60.0(51.0, 66.0)) years, including 119 (58.6%) males. Over a follow-up of (98.2±30.9) months, 39 patients experienced MACE. Maxstat identified an optimal cut-off value of 34.3° for the ostial angle of the anomalous vessel. Multivariable Cox proportional hazards regression analysis revealed that the following factors were independent risk factors for MACE: left-sided ACAOS subtype ( HR=4.35, 95% CI 2.17-8.73, P<0.001), an interarterial course between the aorta and pulmonary artery ( HR=3.21, 95% CI 1.23-8.37, P=0.017), an anomalous vessel ostial angle <34.3° ( HR=2.62, 95% CI 1.18-5.77, P=0.017), and concomitant coronary artery disease ( HR=2.92, 95% CI 1.49-5.73, P=0.002). Conclusion:In middle-aged and elderly patients with ACAOS, the imaging anatomical features of a left-sided ACAOS subtype, an interarterial course, and an ostial angle <34.3° are independent risk factors for MACE.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.