In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Megestrol acetate is widely used in clinical practice and offers benefits to patients. However, it carries potential adverse effects, such as hypoadrenocorticism, which is often overlooked due to its atypical clinical manifestations. This report describes two cases of megestrol acetate-induced hypoadrenocorticism. Through a review of relevant literature, the mechanisms, clinical characteristics, and treatment strategies are summarized to enhance clinicians′ awareness of this potential complication.

Objective:To identify the influencing factors for acute kidney injury (AKI) in patients undergoing interventional embolization of intracranial aneurysms under general anesthesia and develop a predictive model.Methods:In this retrospective study, the clinical data from patients who underwent elective interventional embolization of intracranial aneurysms at Hospital Affiliated to Nanjing Medical University from January 2019 to December 2023 were collected. All the patients were divided into AKI group and non-AKI group based on whether AKI occurred postoperatively. The general data, preoperative laboratory parameters, and intraoperative parameters of the patients were obtained through the electronic medical record system and operation-anesthesia management system. The variables screened using LASSO regression were included in the multivariate logistic regression analysis to identify the risk factors for AKI following embolization of cerebrovascular aneurysms. Based on the results, a predictive model was established and evaluated.Results:A total of 428 patients were collected, with 73 in AKI group and 355 in non-AKI group. LASSO regression for variable selection and multivariate logistic regression analysis showed that serum creatinine concentration, duration of surgery and age were independent risk factors, and the glomerular filtration rate and hemoglobin concentration were protective factors for AKI after interventional embolization of intracranial aneurysms ( P<0.05). The area under the receiver operating characteristic curve of the prediction model was 0.860 (95% confidence interval 0.815 to 0.905), with a sensitivity of 0.880 and a specificity of 0.718. The calibration curve showed a mean absolute error of 0.014. The Hosmer-Lemeshow goodness-of-fit test indicated that there was no statistically significant difference between the predicted and observed values of the model ( χ2=3.29, P=0.915). The clinical decision curve demonstrated that the net benefit rate for patients was higher when the threshold probability ranged from 0 to 0.83. Conclusions:The glomerular filtration rate, serum creatinine concentration, hemoglobin concentration, duration of surgery and age are influencing factors for AKI following interventional embolization of intracranial aneurysms, and the prediction model established based on these factors demonstrates good predictive performance.

Objective:This study aimed to identify key genes in endothelial cell (EC) associated with the pathogenesis and progression of human venous malformations (VMs) through bioinformatics analysis, providing potential biomarkers for early screening and targeted therapy of VMs.Methods:A case-control study was conducted using surgically resected tissue specimens from VMs patients at the Third Affiliated Hospital of Zhengzhou University (from September 2021 to September 2023), with malformed venous tissues as the experimental group and distal normal venous tissues as controls. Single-nucleus RNA sequencing (snRNA-seq) was performed on paired experimental and control samples from four VM patients. High-dimensional weighted gene co-expression network analysis (hdWGCNA), combined with gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) network analysis, identified critical genes. Validation experiments included 15 additional VM cases and controls using reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and Western blot.Results:A total of 55 430 nuclei were captured using snRNA-seq, with 30 391 nuclei from the experimental group and 25 039 nuclei from the control group. Cluster analysis identified 22 distinct cell populations, which were annotated into 8 cell types. hdWGCNA revealed four modules associated with invasion, which were enriched in angiogenesis, integrin signaling, and cell adhesion according to GO analysis. KEGG pathway analysis indicated that the PI3K-AKT signaling pathway and focal adhesion are key regulatory mechanisms. PPI network analysis combined with cytoscape identified EGFL7, TEK, and FLT1 as key genes. RT-qPCR results demonstrated that the relative mRNA expression levels of these three genes in the experimental group (6.66±2.31, 1.86±0.62, 3.49±0.58) were significantly higher than those in the control group (1.05±0.14, 1.00±0.14, 1.06±0.25), with statistically significant differences ( t=9.37, 4.27, 11.20, P<0.05). Immunohistochemical analysis showed that the relative protein expression levels of these three genes in the cytoplasm of the experimental group (0.84±0.15, 0.68±0.14, 0.85±0.12) were also significantly higher than those in the control group (0.19±0.05, 0.23±0.06, 0.30±0.05), with statistically significant differences ( t=16.62, 5.93, 11.68, P<0.05). Western blot analysis confirmed that the relative protein expression levels of these three genes in the experimental group (0.35±0.04, 0.36±0.09, 0.31±0.04) were significantly higher than those in the control group (0.19±0.01, 0.13±0.02, 0.14±0.04), with statistically significant differences ( t=7.05, 4.61, 5.93, P<0.05). Conclusion:EGFL7, FLT1, and TEK in EC may play crucial roles in the occurrence and invasion of VMs.

To evaluate the clinical application value of magnetic bead sorting technology (MBS) using the T-cell select kit combined with an automatic cell sorter for isolating peripheral blood mononuclear cells (PBMCs) to realize automated specimen pre-processing and process optimization in T-SPOT.TB assay. A cross-sectional study was conducted involving 300 patients recruited from the first affiliated hospital of Air Force Medical University from March 2023 to July 2024. Among them, there were 167 males and 133 females. The age range of the patients was 18 to 65 years, with a median age of 49.0 (33.3, 59.0) years and a mean age of (46.4±13.9) years. 4 ml of anticoagulated whole blood samples in duplicate were collected from each patient. One fresh sample (0-4 h) was processed immediately using density gradient centrifugation (DGC) for PBMC isolation, while the other was processed using MBS method at either 0-4 h or 34-54 h post-collection. The cycles for cell enrichment step of the automatic cell sorter were adjusted from the conventional 4 cycles to 2 cycles. Statistical analysis was performed using Cohen′s Kappa test to evaluate the concordance of T-SPOT.TB results across all processing groups. The results showed that for fresh samples (0-4 h), the T-SPOT.TB results for samples processed with 4-cycle and 2-cycle MBS enrichment steps demonstrated positive concordance rates of 91.7% and 93.1%, negative concordance rates of 100% for both, overall concordance rates of 98.0% and 97.9%, and Kappa values of 0.94 and 0.95, respectively, compared with the reference results for paired samples processed using DGC. Correspondingly, the results for samples processed with the 4-cycle and 2-cycle MBS methods at 34-54 h post-collection yielded positive concordance rates of 90.0% and 81.3%, negative concordance rates of 95.1% and 100%, overall concordance rates of 93.0% and 82.9%, and Kappa values of 0.86 and 0.43, respectively, compared with the reference results for fresh samples processed using DGC. In conclusion,for 0-4 h samples, the T-SPOT.TB results from both 4-cycle and 2-cycle MBS enrichment protocols were highly consistent with the reference results from conventional DGC methods. However, for 34-54 h stored samples, results from the 4-cycle MBS method rather than the 2-cycle protocol exhibited significantly superior concordance with the reference results. The MBS method using T-Cell Select kit achieves automated sample pre-processing for T-SPOT.TB assay, reduces hands-on time, and provides a viable alternative with reliable results for long-stored specimens.

In recent years,the microorganisms residues in endoscopes have frequently resulted in cross transmis-sion or even the outbreak of hospital-associated infections.It is of great importance to carry out standardized bio-logical surveillance of endoscopes,find out the high-risk links of cleaning and disinfection,and take targeted inter-vention measures to reduce the incidence of endoscopy-related infection.Based on the related guidelines in China and abroad as well as the latest clinical practice researches,the biological surveillance sampling and culture for en-doscopes were summarized in the article so as to enhance the surveillance quality,ensure the reprocessing effect and guarantee the endoscopy-related quality and safety.

ln the context of the high-quality development of public hospitals,research management is transitioning from a results-oriented approach to a full-process management model,necessitating the exploration of a governance system that integrates topic guidance,process support,and outcome transformation.Based on the Knowledge-to-Action and SECl model,it analyzes the construction logic and application effectiveness of the nursing research rounds mechanism at a teritary grade A hospital in Hainan Province.Through a"three-tier stratification+dual-track collaboration+full-process closed-loop"design,the mechanism bridges the chain from"clinical problem identification to research path optimization to outcome transformation",significantly enhancing research participation,research plan standardization,and research output.The findings validate the practical value of the research rounds mechanism in promoting knowledge transformation,capability enhancement,and organizational knowledge retention.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

Thyroid cancer is the only non reproductive tumor that mainly occurs in women.The morbidity rate of female thyroid cancer is three times higher than that of male thyroid cancer.However,the ex-isting studies have not systematically summarized the factors that contribute to the high incidence of thyroid cancer in women.This paper reviews all the literatures that mention the high incidence of thyroid cancer in women,and sorts out the main reasons,such as estrogen,obesity,reproductive factors,oxidation antioxidant system imbalance,X chromosome,etc.,which are the main reasons for the current research finding that the in-cidence rate of thyroid cancer in women is higher than that in men.This paper makes a vivid graphic analysis and summary of the reasons,providing a research direction for future researchers to research on gender duality of thyroid cancer,and providing a certain reference for the clinical diagnosis and treatment of gender differences in thyroid cancer.