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*

Objective:To investigate the efficacy and safety of bridging thrombectomy and direct thrombectomy in patients with acute anterior circulation large core infarction.Methods:A retrospective cross-sectional study was performed; 131 patients with acute anterior circulation large core infarction with an onset time≤ 24 hours received endovascular treatment (EVT) at Department of Intervention Neurosurgery, Nanyang Central Hospital, Xinxiang Medical University, from June 2022 to June 2024 were chosen; they were divided into bridging thrombectomy group (accepted intravenous thrombolysis [IVT] before EVT, n=55) and direct thrombectomy group ( n=76). Statistical analysis was conducted to compare the differences in efficacy and safety between the two groups. Efficacy indicators included modified Rankin scale (mRS) score 90 days after thrombectomy, and good prognosis rate 90 days after thrombectomy (mRS scores of 0-2). Safety indicators included intracranial hemorrhage (ICH) incidence within 72 hours of thrombectomy, symptomatic intracranial hemorrhage (sICH) incidence within 72 hours of thrombectomy, mortality 90 days after thrombectomy, and ratio of patients receiving decompressive craniectomy after surgery. Results:No significant difference between the direct thrombectomy group and bridging thrombectomy group was noted in terms of mRS score 90 days after thrombectomy (3 [2, 6] vs. 3 [2, 6]), good prognosis rate 90 days after thrombectomy (38.2% vs. 25.5%), ICH incidence within 72 hours of thrombectomy (30.3% vs. 40.0%), sICH incidence within 72 hours of thrombectomy (21.1% vs. 21.8%), mortality rate within 90 days of thrombectomy (28.9% vs. 25.5%), and ratio of patients receiving decompressive craniectomy after surgery (9.2% vs. 9.1%, P>0.05). Core infarction volume at 100 mL was used as grouping standard, subgroup analysis showed that when the core infarction volume was 70-100 mL and >100 mL, respectively, no significant difference in sICH incidence was noted between the bridging thrombectomy group and direct thrombectomy group ( P>0.05). Conclusion:For patients with acute anterior circulation large core infarction with an onset time≤ 24 hours, bridging thrombectomy has similar efficacy and safety as direct thrombectomy.

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.

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 To explore the distribution and drug resistance of the pathogens causing the abdominal(pelvic)soft tissue infections in secondary or above medical institutions of Suzhou so as to provide bases for pre-vention and control of the infections.METHODS The surveillance data of abdominal(pelvic)soft tissue infections that were reported regularly from 58 member institutions of Suzhou from Jan.2020 to Dec.2023 were collected from the regional nosocomial infection surveillance platform by Suzhou nosocomial infection management and qual-ity control center.Totally 26 tertiary hospitals and 32 secondary hospitals were involved.RESULTS Most of the 1178 strains of pathogens were isolated from the tertiary hospitals,the proportion of gram-negative bacteria was the highest;Escherichia coli,Klebsiella pneumoniae and Enterococcus faecium ranked the top 3 species.The constituent ratio of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains the was highest among the mul-tidrug-resistant organisms.The K.pneumoniae and CRKP strains were sensitive to tigecycline;the E.coli strains were highly sensitive to carbapenems,minocycline and piperacillin-tazobactam;Stenotrophomonas maltophilia strains were highly resistant to most of the antibiotics;Enterobacter cloacae strains were highly resistant to ampi-cillin-sulbactam but were highly sensitive to carbapenems;the drug resistance rate of the A.baumannii strains to tigecycline was less than 5％;the drug resistance rate of Pseudomonas aeruginosa strains to ticarcillin-clavulanic acid was highest.CONCLUSIONS The abdominal(pelvic)soft tissue infection is always mixed infections.The pathogens show severe drug resistance.It is necessary to strengthen the surveillance of etiological spectrum and drug resistance and conduct targeted guidance for clinical practice of diagnosis and treatment.

Objective:To explore the clinical and genetic characteristics and follow-up status of pediatric patients with hepatic glycogen storage disease in order to further improve the prognosis.Methods:The clinical data of hospitalized children diagnosed with hepatic glycogen storage disease in the Department of Gastroenterology at the Children's Hospital of Capital Institute of Pediatrics from January 2010 to April 2023 were collected and retrospectively analyzed. The results of laboratory examination and gene sequencing were analyzed, and the number of cases that exceeded three (n) were grouped according to the genetic results: Group 1 was type Ⅰ ( n=8), Group 2 was type Ⅲ ( n=5), and Group 3 was type Ⅸa ( n=8).The growth, development and prognosis of the children were followed up. The related clinical characteristics of pediatric hepatic glycogen storage disease were summarized. Results:Twenty-five pediatric patients with hepatic glycogen storage disease were enrolled in this study, with fifteen males and ten females. The mean age of diagnosis was (29.1±13.5) months. There were twelve cases (48%) accompanied with varying degrees of hypoglycemia, and two cases (8%) with severe hypoglycemia.There were nineteen cases with stature retardation (76%), four cases with anemia (16%), three cases with proteinuria (12%), and one case with cholestasis (4%).The genetic results showed that there were four cases of type Ⅰa (16%), four cases of type Ⅰb (16%), one case of type Ⅱ (4%), five cases of type Ⅲ (20%), two cases of type Ⅳ (8%), one case of type Ⅵ (4%), and eight cases of type Ⅸ (32%).The three subgroups analysis showed that there were significant statistical differences in uric acid and triglycerides among the three groups ( P<0.05), while there were no statistical significant differences in transaminase levels, fasting blood glucose, lactate, cholesterol, and low-density lipoprotein levels ( P>0.05). The height-for-age Z scores of the three groups were -2.86±1.62, -1.46±1.06, and -1.83±0.98, respectively. The growth and development of groups 2 and 3 were significantly improved compared with group 1 ( P<0.05), with Z scores of -2.28±1.07, 0.20±1.54, and 0.10±1.44 after at least one year of follow-up. All pediatric patients with type Ⅸa had discontinued using raw corn starch after more than one year of follow-up and their transaminases had returned to normal. Four pediatric patients with type Ia were orally administered raw corn starch on a regular basis, and the aminotransferases, uric acid, and lactate were normal, with hypoglycemia being monitored. Among the four cases with type Ⅰb, one had recurrent respiratory tract and intestinal infections, two were combined with Crohn's disease, and one was monitored for hypoglycemia. In four cases of type Ⅲ, raw corn starch was discontinued, and a high-protein, low-carbohydrate diet was adopted, with the exception of the presence of high creatine kinase and normal aminotransferase. Liver failure resulted in the death of one type Ⅵ case, while two were type Ⅳ cases; one died, and one case recently had slightly elevated aminotransferase. Conclusion:When pediatric patients exhibit manifestations such as hepatomegaly, elevated transaminases, fasting hypoglycemia, and delayed growth and development, it is necessary to be alert to hepatic glycogen storage disease. Clinical manifestations and biochemical indicators combined with genetic testing are helpful for the diagnosis of hepatic glycogen storage disease. Simultaneously, targeted nutritional management should be carried out according to the metabolic characteristics of different subtypes, with attention on growth and development status.

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.