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Abstract A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57–0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

Abstract Background Patients newly diagnosed with lung adenocarcinoma with bone metastases (LABM) have poor survival rates after treatment with conventional therapies. To improve outcomes, we retrospectively investigated whether the application of a more comprehensive genetic test of tumor biopsies samples from LABM patients could provide the basis for treatment with more effective tyrosine kinase inhibitors (TKIs) regimens. Methods Fine needle biopsies were taken from the primary tumor (PT) and a secondary bone metastasis (BM) of 17 LABM patients before treatment. Simple genetic profiles for selecting therapies were initially obtained using an ARMS-PCR test for EGFR and ALK fusion mutations. More detailed genetic profiles of somatic exon SNVs and CNVs in 457 cancer-related genes were retrospectively derived using capture single molecule amplification and resequencing technology (capSMART). Results ARMS-PCR identified 14 EGFR positive, 3 EGFR negative and 1 ALK fusion positive patient. A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively. With the exception of two patients, molecular profiling of matching PT and BM biopsies identified a highly shared somatic variant fingerprint, although the BMs exhibited additional genomic instability. In six of 13 EGFR positive patients and in all three EGFR negative patients, examination of the genetic profiles identified additional clinically significant mutations that are known or experimental drug targets for treatment of lung cancer. Conclusion Our findings firstly suggest that treatment regimens based on comprehensive genetic assessment of newly diagnosed LABM patients should target both the PT and secondary BMs, including rogue clones with potential to form new BMs. Second, the additional information gained should allow clinicians to design and implement more personalized treatment regimens and potentially improve outcomes for LABM patients.

Abstract Background The standard treatment for esthesioneuroblastoma, a rare malignant nasal vault neoplasm, is not established. Methods We retrospectively assessed the clinicopathological features, prognostic factors and treatment methods for 187 patients with esthesioneuroblastoma treated in China between 1981 and 2015. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank tests. Results Twenty-three (12.3%), 48 (25.7%) and 113 (60.4%) patients had Kadish stage A, B and C esthesioneuroblastoma; 3 (1.6%) had unknown stage. Overall, 117 (62.6%) patients received surgery and combined radiotherapy with or without chemotherapy; 35 (18.7%) received radiotherapy with or without chemotherapy; 32 (17.1%) received surgery alone; and 3 (1.6%) received palliative treatment. Three-year OS and DFS for the entire cohort were 66.7% and 57.5%, respectively. Three-year OS for stage A, B and C were 91.3%, 91.2% and 49.5% (P

Triple negative breast cancer (TNBC) acquires an unfavorable prognosis, emerging as a major challenge for the treatment of breast cancer. In the present study, 122 TNBC patients were subjected to analysis of Aurora-A (Aur-A) expression and survival prognosis. We found that Aur-A high expression was positively associated with initial clinical stage (P = 0.025), the proliferation marker Ki-67 (P = 0.001), and the recurrence rate of TNBC patients (P

BACKGROUND: Poisoned patients often suffer damage to multiple systems, and those experiencing central nervous system disorders present more severe conditions, prolonged hospital stays, and increased mortality rates. We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy. METHODS: This retrospective, observational, comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University, from October 2020 to December 2022. Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included, and patients were divided into three subgroups according to Glasgow Coma Scale (GCS). Demographic and clinical characteristics were collected. The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status (Glasgow Coma Scale [GCS] score), muscle strength and movement and swallowing function (Fugl-Meyer Assessment [FMA] scale, Water Swallow Test [WST], and Standardized Swallowing Assessment [SSA]). Subgroup analysis was based on different toxic species. RESULTS: Out of the 464 patients with toxic encephalopathy, 184 cases received rehabilitation treatments. For the severe toxic encephalopathy patients, patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention (Hazard ratio [HR]=2.21). Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning (P=0.02), while no significant improvement was observed in patients with drug/biological agent poisoning (P=0.44). After rehabilitation intervention, significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy (P<0.01). CONCLUSION: Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice. [ABSTRACT FROM AUTHOR]

Gallic acid is an important secondary metabolite in plants, with great value in medicine, food, and chemical industry. However, whether and how this widely existing natural polyphenolic compound affects the growth and development of plants themselves remains elusive. In this study, we revealed that exogenous application of gallic acid has a dual effect on the elongation of primary root in Arabidopsis. While lower concentrations of gallic acid slightly stimulate primary root growth, excessive gallic acid profoundly reduces primary root length and root meristem size in a dose-dependent manner, probably via suppressing cell division in root meristem as indicated by CYCB1;1::GUS. Moreover, as suggested by the DR5::GFP line analysis and confirmed by the LC-MS assay, auxin contents in root tips were dramatically decreased upon excessive gallic acid treatment. Additional application of IAA partially rescued the shortened primary root and root meristem upon excessive gallic acid treatment, suggesting that auxin is required for excessive gallic acid-caused root growth inhibition. Then, we further revealed that excessive gallic acid down-regulated the expression of auxin transporters PIN1, PIN2, PIN3, and PIN7, and triple mutant pin1 pin3 pin7 exhibited a reduced sensitivity to gallic acid treatment. Meanwhile, excessive gallic acid decreased the degradation of AXR3/IAA17 protein as revealed by HS:: AXR3NT-GUS reporter line. Auxin signaling mutant tir1 afb2 afb3 and axr3-3 were also less sensitive to excessive gallic acid treatment in terms of primary root length and root meristem size. Taken together, these findings suggested that excessive gallic acid inhibits primary root growth by modulating auxin transport and signaling in Arabidopsis. [ABSTRACT FROM AUTHOR]

Chinese nursing education levels have developed fast over the past few years. Many nursing educators are devoted to the research of nursing teaching. How to cultivate nursing students, creative thinking is one of the principle researches and has received increasing attention. In the course of nursing teaching, we renewed the teaching design based on the empirical education from nursing basics as follows. The teaching contents are enlarged to make students establish a sense of nursing development and dynamic study. The traditional teacher-centered teaching methods have been replaced by diversified students-centered methods from knowledge to activities. Evaluation of learning effect is developed to be a versatile comprehensive evaluation including students' self-evaluation in accord with the multimedia teaching, group-evaluation in theoretical and discussion classes, and teachers' all-around evaluation. The new teaching design have embodied students' principal role and enhanced their abilities of creative thinking.

We illustrated a rare case of malignant solitary fibrous tumor (MSFT) with epithelioid morphology in the occipital region of a 59-year-old female, in which a rare NAB2ex7-STAT6 exon15/16 double fusion subtype was detected by the Next-generation sequencing (NGS) and STAT6 immunohistochemistry (IHC) was diffusely and strongly positively expressed, without recurrence after 20 months of postoperative follow-up. The morphological and molecular genetic aspects and the differential diagnosis are described, and the relevant literature was assessed in order to broaden our understanding and diagnostic capability of this malignancy [ABSTRACT FROM AUTHOR]

Introduction: In the context of ongoing discussions in Chongqing (China) about urban development strategies for the city's transit system, this paper introduces an empirical framework for assessing the development of urban transit stations in mountainous cities. Cities in mountainous areas possess unique natural topography, development patterns, cultures, and natural resources, leading to distinct urban development characteristics compared to cities built on plains. Methods: Drawing on the node-place modelling literature, we develop a multidimensional station assessment methodology adapted for mountainous cities. By adding the dimension of pedestrian experience, we propose indicators that represent the unique challenges of accessing stations in such terrains that are not typically reflected in conventional node-place analysis. Results: Our findings reveal station-specific development opportunities in greater detail and can guide more targeted planning for land use around stations. Discussion: Our assessment method is particularly useful for cities facing terrain challenges that impact pedestrian experience. [ABSTRACT FROM AUTHOR]

Background: Some observational studies and clinical experiments suggest a close association between gut microbiota and metabolic diseases. However, the causal effects of gut microbiota on adrenal diseases, including Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism, remain unclear. Methods: This study conducted a two-sample Mendelian randomization analysis using summary statistics data of gut microbiota from a large-scale genome-wide association study conducted by the MiBioGen Consortium. Summary statistics data for the three adrenal diseases were obtained from the FinnGen study. The study employed Inverse variance weighting, MR-Egger, and MR-PRESSO methods to assess the causal relationship between gut microbiota and these three adrenal diseases. Additionally, a reverse Mendelian randomization analysis was performed for bacteria found to have a causal relationship with these three adrenal diseases in the forward Mendelian randomization analysis. Cochran's Q statistic was used to test for heterogeneity of instrumental variables. Results: The IVW test results demonstrate that class Deltaproteobacteria, Family Desulfovibrionaceae, and Order Desulfovibrionales exhibit protective effects against adrenocortical insufficiency. Conversely, Family Porphyromonadaceae, Genus Lachnoclostridium, and Order MollicutesRF9 are associated with an increased risk of adrenocortical insufficiency. Additionally, Family Acidaminococcaceae confers a certain level of protection against Cushing syndrome. In contrast, Class Methanobacteria, Family Lactobacillaceae, Family Methanobacteriaceae, Genus. Lactobacillus and Order Methanobacteriales are protective against Hyperaldosteronism. Conversely, Genus Parasutterella, Genus Peptococcus, and Genus Veillonella are identified as risk factors for Hyperaldosteronism. Conclusions: This two-sample Mendelian randomization analysis revealed a causal relationship between microbial taxa such as Deltaproteobacteria and Desulfovibrionaceae and Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism. These findings offer new avenues for comprehending the development of adrenal diseases mediated by gut microbiota. [ABSTRACT FROM AUTHOR]

Inversion of ionograms from vertical measurements is significant for studying the ionospheric structure and ionospheric wave propagation, and it has attracted widespread attention. The model method is a relatively common inversion method for vertical ionograms. In this paper, a model inversion algorithm based on the multivariate QP model (single quasi-parabolic ionospheric profile model) is proposed, which is different from the traditional QPS model (where the multiple quasi-parabolic segment ionospheric profile model uses quasi-parabolic or anti-parabolic models to represent E, valley, and F1 and F2 layers). In other words, the electron density height profile of each layer in the ionosphere is no longer described by a single QP model. Still, it is based on QP as the basic unit and characterized by a combination of multiple QP units, and the entire vertical ionospheric profile consists of a series of QP unit models. Moreover, in the case of the multivariate QP model, determining the parameters of each layer becomes more complex. This study provides a more straightforward method, which can determine the entire QP unit profile by selecting one of the three parameters of each unit QP. Based on this model, the inversion of vertical ionograms was achieved, and the effectiveness of the inversion algorithm was verified based on typical vertical ionogram data. [ABSTRACT FROM AUTHOR]