Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/immunology* ; Carcinoma, Non-Small-Cell Lung/immunology* ; Small Cell Lung Carcinoma/genetics* ; Male ; Middle Aged ; Female

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Astragalus membranaceus possesses the function of enhancing immunity, protecting the liver, diuretic, anti-aging, anti-stress, anti-hypertensive, and more extensive antibacterial effects. Polysaccharides, one kind of the major active ingredients of A. membranaceus, are considered to be responsible for their versatile use. Now, a systematic summary of research progress and prospects of polysaccharides from A. membranaceus polysaccharides (AMPs) is necessary to facilitate their further study and application. In this review, the optimal extraction methods, structural features, biological activities, and applications of AMPs were emphasized. The structure-activity relationships are also analyzed and elucidated. Solvent, ultrasonic, microwave, enzyme-assisted, ultra-high pressure, and combined methods have been used to extract AMPs. Among them, solvent extraction is the most commonly used method because it is simple and easy to operate, but the efficiency needs to be improved further. The ultra-high pressure method is the most efficient but has a low economic return. AMPs exhibited various bioactivities, including immunomodulation, antitumor, and antidiabete. The structure-activity relationships revealed that different structure configurations, chain conformations, and physical properties would have different bioactivities. However, the new method for purification of certain polysaccharides, detailed structure-activity relationships (SAR), mechanisms of bioactivities, and quality control of AMPs need to be extensively investigated.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

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The long-term presence of non-steroidal anti-inflammatory drugs (NSAIDs) in the environmental water samples not only affects the life safety of aquatic organisms and disturbs the ecoenvironment, but also poses a serious threat to human health. In this study, amino-functionalized Fe3O4 nanoparticles (Fe3O4-NH2) were firstly prepared by solvothermal method. Subsequently, polyethyleneimine (PEI) with a branched chain structure was successfully grafted onto Fe3O4 nanoparticles by Schiff base reaction in aqueous solution at room temperature using glutaraldehyde as a cross-linking agent, and a recyclable PEI-grafted magnetic nano-sorbent (Fe3O4@PEI) was synthesized and applied for the detection of NSAIDs in the environmental water samples. The compositional properties of Fe3O4@PEI were investigated by different characterization methods and the parameters affecting the extraction of NSAIDs were optimized. Due to high adsorption of Fe3O4@PEI for NSAIDs, the quantitative analysis of four NSAIDs in the environmental water samples, ketoprofen, naproxen, diclofenac and tolfenamic acid, was performed in combination with high-performance liquid chromatography. A good linear relationship between the chromatographic peak area and concentration was observed in the range of 1−500 µg/mL. The recoveries of the samples at three different spiked levels ranged from 85.6% to 107.8%; the intra-day precision was less than 7.8% (n=6); and the inter-day precision was less than 9.5% (n=3). The method is simple, rapid, accurate and reliable, and can be used for the analysis of NSAIDs in the environmental water samples．

ObjectiveIn order to improve the recognition accuracy of named entities in medical record texts and realize the effective mining and utilization of medical record knowledge， a Bert-Radical-Lexicon（BRL） neural network model is constructed to recognize medical record entities with respect to the characteristics of medical record texts. MethodWe selected 408 medical records related to hypertension from the the Complete Library of Famous Medical Records of Chinese Dynasties and constructed a dataset consisting of 1 672 medical records by manually labeling. Then， we randomly divided the dataset into three subsets， including the training set（1 004 cases）， the testing set （334 cases） and the validation set（334 cases）. Based on this dataset， we built a BRL model that fused various text features of medical records， as well as its variants BRL-B， BRL-L and BRL-R， and a baseline model Base for experiments. During the model training phase， we trained the above models using the training set to reduce the risk of overfitting. We continuously monitored the performance of each model on the validation set during training and saved the model with the best performance. Finally， we evaluated the performance of these models on the testing set. ResultCompared with other models， the BRL model had the best performance in the medical records named entity recognition task， with an overall recognition precision of 90.09%， a recall of 90.61%， and the harmonic mean of the precision and recall（F1） of 90.35% for eight types of entities， including disease， symptom， tongue manifestation， pulse condition， syndrome， method of treatment， prescription and traditional Chinese medicine（TCM）. Compared with the Base model， the BRL model improved the overall F1 value of entity recognition by 5.22%， and the F1 value of pulse condition entity increased by 6.92%， which was the largest increase. ConclusionBy incorporating a variety of medical record text features in the embedding layer， the BRL neural network model has stronger named entity recognition ability， and thus extracts more accurate and reliable TCM clinical information.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

BACKGROUND:Photothermal therapy is a novel tumor treatment strategy that uses photothermal agents to transform light energy into heat energy to accomplish non-invasive tumor ablation.The rise of photothermal therapy and nanotechnology has provided a new perspective on breast cancer treatment.OBJECTIVE:To prepare a new type of near-infrared biomimetic nanoprobe that has been modified by breast cancer cell membrane,to investigate the effect of near-infrared fluorescence/ultrasound imaging in vitro,and to observe its targeting ability and photothermal therapy effect on homologous tumor cells in vitro.METHODS:Organic small molecule ITIC-4CI with A-D-A structure was used as photothermal agents;polylactic acid/glycolic acid copolymer as nanocarrier;4T1 cell membrane of mouse breast cancer cells as a surface modifier of nanoparticles;perfluorohexane(PFH)was loaded.A novel near-infrared biomimetic nanoprobe(4T1m/ITIC-4CI/PFH)was prepared by the double emulsion evaporation method and sonication method.The basic characterization of the nanoprobe and the homologous targeting ability were detected.The photothermal properties and photothermal stability of the probe were investigated,and the near-infrared fluorescence/ultrasound imaging effect of the probe under laser irradiation was observed.The CCK-8 assay and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.RESULTS AND CONCLUSION:(1)The prepared 4T1m/ITIC-4CI/PFH nanoprobes had uniform size,high stability,and an average particle size of(92.7±2.3)nm.The probe's protein composition was identical to that of the 4T1 cell membrane.The nanoprobe's ability to target homologous 4T1 cells was validated by an in vitro cell uptake assay.(2)The nanoprobe had a red-shift absorption spectrum and tail emission extending to the near-infrared-Ⅱ,which emitted a bright near-infrared-Ⅱ fluorescence signal under laser irradiation.(3)After laser irradiation,the nanoprobe 4T1m/ITIC-4CI/PFH could be turned into microbubbles and enhanced ultrasound imaging.The results of CCK-8 assay and calcein/propidium iodide staining showed that the nanoprobe 4T1m/ITIC-4CI/PFH had an obvious photothermal killing effect on 4T1 cells.(4)The results show that the nanoprobe 4T1m/ITIC-4CI/PFH has the ability to target homologous tumors and enhance near-infrared-Ⅱ fluorescence imaging/ultrasound imaging and photothermal therapy effects.

The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.