Importance Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. Objective To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Design, Setting, and Participants Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. Main Outcomes and Measures The primary end point was overall survival time from randomization. Results Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%). Conclusions and Relevance Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo. Trial Registration ClinicalTrials.gov Identifier: NCT03745170
This study was designed to discuss feasibility, short-term efficacy, and complications of iodine-125 radioactive seed tissue implantation for remedying recurrent cervical cancer.From June 2009 to December 2010, 17 patients with recurrent cervical cancer received radioactive seed implantation under computed tomography (CT) guidance. Matched peripheral dose was 145 Gy, while the number of implanted seeds was from 6 to 68 with a median of 20. Efficacy was determined based on the results of CT and 18 F-fluorodeoxyglucose positron emission tomography/CT.Postoperative follow-ups were from 4 to 18 months with a median follow-up time of 9.5 months. Nine patients died during follow-up while remaining patients survived during the follow-up period. Evaluation of efficacy: six patients had a complete response, four patients had a partial response, and seven patients had progressive disease, clinical efficacy rate as 58% (10/17). No patients had complications of radiation injury. Rate of 6 months and 1-year survival period was 74.8% and 18.3%, respectively. Comparing to patients who responded ineffectively to radioactive seed implantation, patients who responded effectively to radioactive seed implantation had a longer survival period (median 7.2 vs. median 10.4), in which the difference was statistically significant (P = 0.038).Iodine-125 radioactive seed tissue implantation is a feasible, effective, and safe treatment method for remedying or palliative treatment of recurrent cervical cancer. Patients who have recurrent cervical cancer and responded effectively to radioactive seed implantation will have a longer survival period.
Abstract Background The role of postoperative radiotherapy in pathological T2–3N0M0 esophageal squamous cell carcinoma is unknown. We aimed to evaluate the efficacy and safety of postoperative radiotherapy in patients with pathological T2–3N0M0 thoracic esophageal squamous cell carcinoma. Materials and Methods Patients aged 18–72 years with pathological stage T2–3N0M0 esophageal squamous cell carcinoma after radical surgery and without neoadjuvant therapy were eligible. Patients were randomly assigned to surgery alone or to receive postoperative radiotherapy of 50.4 Gy in supraclavicular field and 56 Gy in mediastinal field in 28 fractions over 6 weeks. The primary endpoint was disease-free survival. The secondary endpoints were local-regional recurrence rate, overall survival, and radiation-related toxicities. Results From October 2012 to February 2018, 167 patients were enrolled in this study. We analyzed 157 patients whose follow-up time was more than 1 year or who had died. The median follow-up time was 45.6 months. The 3-year disease-free survival rates were 75.1% (95% confidence interval [CI] 65.9–85.5) in the postoperative radiotherapy group and 58.7% (95% CI 48.2–71.5) in the surgery group (hazard ratio 0.53, 95% CI 0.30–0.94, p = .030). Local-regional recurrence rate decreased significantly in the radiotherapy group (10.0% vs. 32.5% in the surgery group, p = .001). The overall survival and distant metastasis rates were not significantly different between two groups. Grade 3 toxicity rate related to radiotherapy was 12.5%. Conclusion Postoperative radiotherapy significantly increased disease-free survival and decreased local regional recurrence rate in patients with pathological T2–3N0M0 thoracic esophageal squamous cell carcinoma with acceptable toxicities in this interim analysis. Further enrollment and follow-up are warranted to validate these findings in this ongoing trial.
Radiotherapy plays an important role in the treatment of glioma, and predicting radiotherapy sensitivity can help physicians develop more individualized treatment plans. However, few studies have used deep learning for glioma radiotherapy sensitivity. To better explore the impact of the relationship between tumor and neighboring regions on radiotherapy, we applied Graph Convolutional Networks (GCN) to explore predicting radiotherapy sensitivity. Firstly, we use the tumor core and the adjacent region as the nodes, where we use the radiotherapy Planning Target Volume (PTV) as the adjacent region. Secondly, we use the relationship between the tumor core and the PTV as the connected edge relationship. Finally, the Radiomics Features of each region are extracted as the node features. In this way, we construct the graph and use GCN to learn the representation of nodes in the graph to capture the structural information and association relationships among nodes for the prediction of radiotherapy sensitivity. In addition, we experimented with different node construction approaches and modular construction models. We used slice-level data to construct the graph and used a hard voting method to predict the labeling of patients. The experimental results show that our proposed node construction approach and GCN model achieve 93% accuracy after voting, which is an 11% improvement in accuracy compared to the traditional classifier.
The purpose of this study is to explore the intelligent application design based on artificial intelligence and adaptive interface. First, we outline the basic principles of artificial intelligence technology and its important role in application design, as well as the basic concepts and principles of adaptive interface design. Then, by analyzing practical cases, we discuss the close combination of artificial intelligence and UI page design, including design practices in the fields of intelligent recommendation system, intelligent voice assistant and intelligent search engine. Through these case studies, we delve into how AI and adaptive interfaces can work together to drive smart and personalized application design. Finally, we summarize the research results and look forward to the development trend and research direction of intelligent application design in the future.
The reliability of power grids is of paramount importance to modern infrastructure. Precise fault location estimation is crucial for the efficient operation and rapid recovery of electrical networks following outages. This paper presents a novel approach using Graph Attention Networks (GAT) to improve fault location estimation within power grids. Leveraging two years of real-world data from a power grid's monitoring system, encompassing 200 fault instances, our model demonstrates a significant advancement over traditional methods. The GAT model capitalizes on an attention-driven mechanism, providing a dynamic and focused analysis of the grid's topological data, which enhances the accuracy of fault detection. Comparative experiments show that GAT model outperforms benchmark algorithms, Graph Convolutional Networks (GCN), and Graph Neural Networks (GNN), with lower Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) metrics. The results highlight the GAT's potential as a robust and reliable tool for fault diagnosis in power grids, promising substantial improvements in operational resilience and maintenance efficiency.
Microwave ablation (MWA) is an effective local treatment for malignant liver tumors; however, its efficacy and safety for liver tumors adjacent to important organs are debatable.Forty-three cases with liver tumors adjacent to important organs were the risk group and 66 cases were the control group. The complications between two groups were compared by chi-square test and t-test. Local tumor recurrence (LTR) was analyzed by log-rank test. Factors affecting complications were analyzed by logistic regression and Spearman analyses. Factors affecting LTR were analyzed by Cox regression analysis. A receiver operating characteristic curve predicted pain treated with drugs and LTR.We found no significant difference in complications and LTR between two groups. The risk group experienced lower ablation energy and more antennas per tumor than control group. Necrosis volume after MWA was positively correlated with pain; necrosis volume and ablation time were positively correlated with recovery duration. Major diameter of tumor >3 cm increased risk of LTR by 3.319-fold, good lipiodol deposition decreased risk of LTR by 73.4%. The area under the curve (AUC) for necrosis volume in predicting pain was 0.74, with a 69.1 cm3 cutoff. AUC for major diameter of tumor in predicting LTR was 0.68, with a 27.02 mm cutoff.MWA on liver tumors in at-risk areas is safe and effective, this is largely affected by proper ablation energy, antennas per tumor, and experienced doctors. LTR is primarily determined by major diameter of tumor and lipiodol deposition status.
Objective
To analyze the epidemiological characteristics of acute paraquat(PQ)poisoning in children in southwest Shandong, and the risk factors for pulmonary interstitial fibrosis.
Methods
This retrospective study was performed on the clinical data of children with acute PQ poisoning admitted from January 2013 to December 2017 in 12 hospitals in southwest Shandong.All participants were divided into pulmonary interstitial fibrosis group and no pulmonary interstitial fibrosis group on the basis of the chest CT 14 days after poisoning.The epidemiological characteristics and risk factors of pulmonary interstitial fibrosis were analyzed.
Results
During the study period, a total of 307 children with acute PQ poisoning were admitted to 12 hospitals, of which 61 (19.87%) were suffering from acute PQ poisoning.Forty-nine cases with complete clinical data were analyzed, including 26 male and 23 female patients poisoned by oral.The age distribution ranged from 8 months to 14 years.Poisoning mainly occured from July to September of each year.The mortality of acute PQ poisoning was 8.2%(4/49), and the incidence of pulmonary interstitial fibrosis in survival patients was 44.4%(20/45). Statistical differences (P<0.05) were found between the pulmonary interstitial fibrosis and no pulmonary interstitial fibrosis, with regard to the times of blood purification, the time from poison exposure to blood purification, the application rate of glucocorticoids, the concentration of PQ in urine, the pediatric critical illness score, the time from poison exposure to gastric lavage, the white blood count at admission, serum creatinine, arterial blood lactate, PaO2, PaCO2, and PaO2/FiO2; however, there was no significant difference in the proportion of blood purification treatment, the mode of blood purification treatment, alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatine kinase and troponin.Stepwise logistic regression analysis showed that the time from exposure to poison to gastric lavage(OR=0.683, 95%CI 0.210-2.222)and to blood purification(OR=0.0133, 95%CI 0.004-0.042), the times of blood purification(OR=2.862, 95%CI 1.450-5.648), concentration of PQ in urine(OR=1.435, 95%CI 1.085-1.898), and the use of glucocorticoids(OR=0.190, 95%CI 0.048-0.757) were the risk factors for pulmonary interstitial fibrosis(P<0.05).
Conclusion
Early gastric lavage and blood purification, increasing the frequence of adminitrating purification appropriately, using low-dose glucocorticoids can reduce the incidence of pulmonary interstitial fibrosis of children with acute PQ poisoning.
Key words:
Paraquat poisoning; Children; Blood purification; Pulmonary interstitial fibrosis; Glucocorticoids
AIM: To investigate the effect of Genistein on epithelial-mesenchymal transdifferentiation (EMT) induced by transforming growth factor-β1 (TGF-βl) in human pancreatic cancer cell line Panc-1, and to explore the mechanism of Genistein inhibiting invasion of Panc-1 cells. METHODS: Panc-1 cells were treated with TGF-β1 and Genistein (0, 1, 25, 50 μmol/L), and those treated with PSB served as controls. Tran-swell chamber assay was performed to determine the invasion ability change of Panc-1 cells. Reverse transcription-polymerase chain reaction (RT-PCR) was used to estimate the mRNA expression of vimentin and E-cadherin. Western bloting assay was used to measure the protein expression of E-cadherin. Cell structure was observed by microscopy. RESULTS: TGF-β1obviously promoted EMT and invasion abilibty of Pane-l cells. Not only the invasion ability but also EMT induced by TGF-β1 were significantly inhibited by Genistein in a dose-dependent manner. The number of Pane-l cells was larger in 0 μmol/L Genistein group than that in the control group (99.16±11.30 vs 65.46±8.99, P＜0.05). Genistein at concentraion of 50 μmol/L down-regulated the mRNA expression of vimentin and up-regulated the mRNA and protein expression of E-cadherin. The characteristic morphology of EMT was reversed. CONCLUSION: Genistein can inhibit TGF-β1-induced invasion of Pane-1 cells remarkably, which may be one of its anti-invasion mechanisms.
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