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Objective@#To improve the N biomarker in the amyloid/taueurodegeneration system by radiomics and study its value for predicting cognitive progression in individuals with mild cognitive impairment (MCI). @*Materials and Methods@#A group of 147 healthy controls (HCs) (72 male; mean age ± standard deviation, 73.7 ± 6.3 years), 197 patients with MCI (114 male; 72.2 ± 7.1 years), and 128 patients with Alzheimer’s disease (AD) (74 male; 73.7 ± 8.4 years) were included. Optimal A, T, and N biomarkers for discriminating HC and AD were selected using receiver operating characteristic (ROC) curve analysis. A radiomics model containing comprehensive information of the whole cerebral cortex and deep nuclei was established to create a new N biomarker. Cerebrospinal fluid (CSF) biomarkers were evaluated to determine the optimal A or T biomarkers. All MCI patients were followed up until AD conversion or for at least 60 months. The predictive value of A, T, and the radiomics-based N biomarker for cognitive progression of MCI to AD were analyzed using Kaplan-Meier estimates and the log-rank test. @*Results@#The radiomics-based N biomarker showed an ROC curve area of 0.998 for discriminating between AD and HC. CSF Aβ42 and p-tau proteins were identified as the optimal A and T biomarkers, respectively. For MCI patients on the Alzheimer’s continuum, isolated A+ was an indicator of cognitive stability, while abnormalities of T and N, separately or simultaneously, indicated a high risk of progression. For MCI patients with suspected non-Alzheimer’s disease pathophysiology, isolated T+ indicated cognitive stability, while the appearance of the radiomics-based N+ indicated a high risk of progression to AD. @*Conclusion@#We proposed a new radiomics-based improved N biomarker that could help identify patients with MCI who are at a higher risk for cognitive progression. In addition, we clarified the value of a single A/T/N biomarker for predicting the cognitive progression of MCI.
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OBJECTIVE To provide the suggestions and reference for the follow-up update of Guiding Principles of Clinical Application of Novel Anti -tumor Drugs （hereinafter referred to as “Guiding Principles ”）. METHODS The update of 2018-2021 editions of Guiding Principles were compared ；the changes of its style ，the variety and quantity of novel anti-tumor drugs ，the classification of indications ，the target ，the inclusion of medical insurance and other aspects were analyzed. Its change trend and possible problems were summarized. RESULTS There was a great change in the style of Guiding Principles in 2020 edition，i.e. deleting the item of “clinical application management ”and adding the item of “attached table ”. Totally 33 novel anti-tumor drugs were included in the 2018 edition of Guiding Principles ，and the number of novel anti-tumor varieties increased to 46，60 and 77 in 2019，2020 and 2021 editions，respectively. The time when the new varieties were included in Guiding Principles was the same year or one year after the domestic market time. Totally 26 varieties of national medical insurance negotiation were included in the 2018 edition of Guiding Principles ，and 8，10 and 12 varieties were added respectively in 2019，2020 and 2021 editions on the basis of the previous edition . Novel anti-tumor drug in the 2018 edition of Guiding Principles mainly focused on traditional targets such as EGFR，HRE2 and VEGFR. However ，since 2019，the number of new targets such as PD-1，PARP，ALK and CDK had been increasing，among which domestic original drugs accounted for a large proportion. CONCLUSIONS The revision of Guiding Principles aims to further guide the clinical application of novel anti-tumor drugs from the professional level of health technology. The new varieties and indications conform to the principles of scientificity and dynamics ；domestic original varieties have developed rapidly ，and innovative varieties to novel target have emerged. The follow-up update of Guiding Principles should refer to authoritative medical guidelines and high-quality evidence- based evidence. Attention should be paid to the types of tumors lacking therapeutic drugs and the clinical value of oushun- novel anti-tumor drugs.
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We present 271 detrital single-grain zircon fission track (ZFT) ages obtained for eight sandstones, which were sampled from the southwestern Yangtze Craton, southern China. Accessory minerals were concentrated using standard crushing, sieving, electro-magnetic and heavy liquid mineral separation techniques. Zircon grains were mounted on FEP Teflon and polished to expose their internal surfaces to 4π geometry. Two to three mounts of each sample were etched in KON:NaOH eutectic melt at â¼228 °C for 12-60 hours to reveal spontaneous fission tracks. Etched mounts were covered with a uranium-free muscovite external detector for the irradiation with thermal neutrons. CN2 standard uranium glasses were embedded with the age standards (Fish Canyon Tuff zircons). After irradiation, external mica detectors were removed from sample mounts and then etched in 48% HF at room temperature for 30 min to reveal induced tracks. Fission track counting was performed using a Zeiss Axiotron microscope at a total magnification of 1250 × . Zircon fission-track ages were calculated using the ζ-calibration technique. The central ages (with 1σ error) vary from 144.7 ± 4.9 Ma to 256.7 ± 9.6 Ma, with variable P(χ2) values of 0%-75%. ZFT ages of the five Cambrian to Ordovician samples are younger than their depositional ages, and thus were fully reset by post-depositional heating. ZFT ages of three Jurassic samples are partially reset, as they overlap with or slightly younger than the corresponding depositional ages.