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 explore the predictive value of radiomics for postoperative pancreatic fistula, infection, and long-term survival in patients with pancreatic ductal adenocarcinoma (PDAC). Methods 206 patients who received radical resection of pancreatic cancer in Zhongshan Hospital, Fudan University from January 2014 to December 2020 and were pathologically confirmed as PDAC after surgery were retrospectively selected, all of whom had complete surgical data and long-term follow-up data. Pyradiomics was used to analyze the enhanced CT images of all patients and extract radiomics features. LASSO dimensionality reduction combined with logistic regression analysis was used to construct a predictive model for pancreatic fistula and abdominal infection after PDAC surgery, and evaluating the model’s effectiveness using ROC curves. A long-term survival prediction model for PDAC patients was constructed using LASSO dimensionality reduction combined with Cox regression analysis, and patient risk scores were calculated. The patients were divided into high-risk and low-risk groups based on the median, and the survival curves were compared to evaluate the effectiveness of the model. The imaging omics features with the highest weight were divided into high expression group and low expression group according to the median, and the prognostic differences and clinical features were compared. Radiomics and clinical features were combined to analyze the influencing factors of long-term prognosis and construct a clinical imaging comprehensive model. Results A total of 1 595 radiomics features were extracted. A predictive model for pancreatic fistula and infection after PDAC surgery was constructed, with AUC values of 0.81 and 0.79, respectively. The PDAC long-term survival prediction model was successfully constructed, and the prognosis of the high-risk group was worse than that of the low-risk group (P<0.001). The weight of the radiomics feature “log-sigma-5-mm-3D_glszm_ZonePercentage” was 59.557. The CA19-9 level in the high expression group is higher than that in the low expression group (P=0.017), and there is a statistically significant difference in survival curves between the two groups (P=0.021). The comprehensive clinical imaging model suggested that age, AJCC stage, lymph infiltration, CA19-9 level and imaging characteristics were risk factors for long-term prognosis of PDAC patients (HR=1.028, 4.084, 2.566, 1.232 and 2.536). Conclusions The predictive model based on radiomics has good predictive performance for pancreatic fistula, infection, and long-term prognosis after PDAC surgery. Patients with high expression of the radiomics feature “log-sigma-5-mm-3D_glszm_ZonePercentage” face poorer prognosis.

Objective:To construct a special training program for oncology nurses on immunotherapy, and to lay the foundation for the promotion of standardized care of immunotherapy.Methods:The first draft of the immunotherapy training program for oncology nurses was initially constructed through literature review and semi-structured interviews; the final draft of the immunotherapy training program for oncology nurses was determined by using the Delphi expert correspondence method from October to December, 2023.Results:Two rounds of expert correspondence were conducted, and the effective recovery rates of the questionnaires were 15/15, with the expert authority coefficients of 0.847 and 0.867, and Kendall harmony coefficients of 0.207 and 0.212, respectively (both P<0.01). The final established special training program for immunotherapy for oncology nurses included 3 primary indicators, 17 secondary indicators, and 58 tertiary indicators. Conclusions:The construction process of the special training program for oncology nurses′immunotherapy is rigorous and scientific, with obvious speciality characteristics, which can provide a feasible program for the training of oncology nurses′immunotherapy nursing.

Objective:To understand the status, evaluation methods and risk factors of economic toxicity in patients with head and neck cancer, in order to provide reference for the construction of follow-up intervention programs.Methods:This scoping review was conducted under the Joanna Briggs Institute in Australia guidelines. Relevant studies were searched in PubMed, Embase, Web of Science, Cochrane Library, Scopus, CINAHL, China National Knowledge Infrastructure, Wanfang Database, VIP Database and Chinese Biomedical Literature Database. Chinese and English literature was screened and summarized from inception to September 21, 2023.Results:A total of 14 articles were included, and the economic toxicity of patients with head and neck cancer was more serious.The evaluation methods were mainly divided into scale evaluation and database data calculation. The risk factors of economic toxicity in patients with head and neck cancer included three aspects: demographic factors such as young age, low education and low income; disease and treatment-related factors such as tumor location in larynx/hypopharynx, current/past use of tube feeding, advanced tumor/distant metastasis; social support factors such as insufficient social security, and so on.Conclusions:Future studies should pay more attention to economic toxicity in patients with head and neck cancer, standardize the selection of assessment tools to reduce heterogeneity, and develop individualized intervention measures for the risk factors of economic toxicity in patients with head and neck cancer, in order to reduce the occurrence of economic toxicity in patients with head and neck cancer.

Objective:To conduct scoping review of related researches on application of somatosensory games in frail elderly people, summarize the intervention elements, outcome indicators and adverse events of somatosensory games, so as to provide reference for related research.Methods:Literature on the application of somatosensory games in frail elderly people was searched from PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang Database, VIP database and China Biology Medicine disc, and the search period was from establishment of databases to July 10, 2023. The included literature was summarized and analyzed.Results:A total of 12 articles were included. Somatosensory game interventions were mainly based on existing commercial game equipment. The frequency of intervention was mainly 2 to 3 times a week, the duration was 20 to 60 minutes, and the course of treatment was 3 to 12 weeks. And most interventions had management or supervision mechanisms. Somatosensory games improved physical function and health-related quality of life in frail elderly people to some extent, but had no effect on mental health. Some studies reported fewer or even no adverse events related to somatosensory gaming intervention, and there were few reports on the feasibility and acceptability of the intervention.Conclusions:Somatosensory games have a certain effect on improving the physical function and health-related quality of life of frail elderly people, and there are fewer adverse events. Future research can draw on existing commercial gaming equipment to develop more scientific, practical and personalized somatosensory games, while improving the evaluation indicators and enhancing intervention effect.

Objective:To analyze the clinical characteristics, diagnosis and treatments of patients with POEMS syndrome initially diagnosed as pulmonary hypertension (PH).Methods:Clinical data of 7 patients who were initially diagnosed as PH and finally diagnosed as POEMS syndrome in Shanghai Pulmonary Hospital from May 2013 to November 2021 were retrospectively reviewed. Clinical manifestations, laboratory tests, echocardiography, hemodynamic findings, treatment and prognosis of patients were analyzed.Results:Seven patients, including 4 males and 3 female, aged (55±9) (44-62) years were presented with elevated pulmonary artery pressure by echocardiography at admission. Chest tightness and shortness of breath (7/7), fatigue (6/7) and lower limb edema (4/7) were the most common symptoms in the first-episode. Meanwhile, patients also presented symptoms associated with POEMS syndrome, including multiple peripheral neuropathy (7/7), multiserosal cavity effusion (6/7), organomegaly (5/7), skin changes (5/7), and endocrine lesions (4/7). Serum levels of vascular endothelial growth factor (VEGF) were significantly increased in all patients. The pulmonary arterial systolic blood pressure was (66±21)mmHg (1 mmHg=0.133 kPa) estimated by echocardiography. Six patients underwent right heart catheterization and significantly increased mean pulmonary artery pressure((35±9) mmHg) was confirmed; and their pulmonary vascular resistance was (4.00±2.10) Wood U. All patients received corresponding treatment for POEMS syndrome. The excise tolerance was improved in 5 patients after successful treatment with stable or reversed WHO functional class. One patient received hemodialysis treatment for uncontrolled POEMS. One patient died during follow-up. The echocardiography was followed up in 4 patients, and 2 of whom had a complete reversal of PH, 1 had a partial reversal, and 1 had not yet reversed.Conclusions:In patients with PH who have multisystem manifestations, such as multiple peripheral neuropathy, multiserosal cavity effusion, organomegaly and skin changes, POEMS syndrome should be considered, and proper and active treatment of POEMS may reverse PH and improve the prognosis of patients.

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Objective:To investigate the treatment and prognosis of patients of G3 non-functional pancreatic neuroendocrine tumors (pNETs) with proliferation index of Ki-67 <55%.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 15 G3 non-functional pNETs patients with proliferation index of Ki-67<55% who were admitted to Zhongshan Hospital of Fudan University from April 2014 to April 2020 were collected. There were 11 males and 4 females, aged (58±10)years. All patients underwent radical resection of the primary lesion. Obser-vation indicators: (1) treatment; (2) postoperative pathological characteristics; (3) follow-up. Measure-ment data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. The Pearson correlation analysis was used to verify the correlation between variables. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Log-Rank test was used for survival analysis. Results:(1) Treatment. All 15 G3 nonfunctional pNETs patients underwent radical resection of the primary lesion of pancreas, including 5 cases receiving pancreati-coduodenectomy, 10 cases receiving distal pancreatectomy with splenectomy. There were 5 patients with simultaneous liver oligometastasis who underwent combined segmental (lobectomy) hepatectomy. All 15 patients had negative tumor margin, and the operation time and volume of intraoperative blood loss of 15 patients was 120(90,210)minutes and 200(50,300)mL, respectively. None of patient had complications ≥Ⅲ grade of the Clavien-Dindo classification during the postoperative 30 days. Of the 15 patients, there were 5 cases receiving comprehensive treatment based on CAPTEM chemo-therapy (temozolomide combined with capecitabine), 2 cases receiving local interventional therapy, 2 cases receiving CAPTEM chemotherapy, 1 case receiving local interventional therapy combined with molecular targeted therapy, 1 case receiving local interventional therapy combined with long acting somatostatin therapy, 1 cases receiving long acting somatostatin therapy combined with molecular targeted therapy, and 3 cases without postoperative treatment. (2) Postoperative patholo-gical characteristics. The tumor diameter of 15 patients was 3.3(range, 0.5-6.0)cm. There were 2 cases with tumor diameter <2 cm, 13 cases with tumor diameter ≥2 cm. The number of lymph nodes dissected and number of lymph nodes metastatic was 6(4, 10) and 2(1,3) in 15 patients, respectively, including 12 cases with positive lymph node metastasis. Of the 15 patients, there were 5 cases with tumor invasion of adjacent organ, 5 cases with simultaneous liver metastasis, 8 cases with perineural invasion and 8 cases with vascular invasion. There were 3, 7, and 5 patients with stage Ⅱ, stage Ⅲ, and stage Ⅳ of pathological TNM staging, respectively. The proliferation index of Ki-67 and mitotic count was 32%±9% and (11±9)/10 high power field in the primary lesion of 15 patients, respectively, and there was no correlation between proliferation index of Ki-67 and mitotic count ( P>0.05). (3) Follow-up. All 15 patients were followed up after surgery for (55±24)months. The median survival time of 15 patients was 78(range, 43-113)months, with 1-, 3-, 5-year overall survival rate as 100%, 92%, 62%, respectively. During the follow up, 9 of the 15 patients underwent tumor recurrence, with the recurrence time as 20(14, 44)months. There were 8 patients died of tumor recurrence or metastasis. The median survival time was 86(range, 51-120)months in 5 patients receiving comprehensive treatment based on CAPTEM chemotherapy, versus 53(range, 45-60)months in 10 patients receiving other postoperative adjuvant therapy or without postoperative treatment, showing a significant difference between them ( χ2=4.21, P<0.05). Conclusion:The prognosis of patients of G3 nonfunctional pNETs with proliferation index of Ki-67<55% undergoing radical resection combined with postoperative comprehensive treatment based on CAPTEM chemotherapy in better than that of patients receiving other postoperative adjuvant therapy or without posto-perative treatment.

Objective:To synthesize the findings of qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy to provide a basis for developing relevant health education strategies and other supportive care interventions.Methods:Qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy, published by May 2022, were searched in English and Chinese databases, including Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, Web of Science, CNKI, Wanfang, VIP, and CBM. The quality of the included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tool for qualitative studies. The research results were summarized and Meta-synthesis using the pooled integration method.Results:A total of 13 articles were included and 62 findings were grouped into 12 new categories according to their similarities. These 12 categories resulted in 4 synthesized findings: life was affected, facing multiple decision scenarios, presence of some unmet needs and gaining positive experiences and personal growth.Conclusions:Although patients experience some positive experiences, a large proportion of them experience significant health distress. Healthcare professionals should develop targeted health education with supportive care strategies on the basis of a comprehensive assessment.

Objective:To explore the current status of humanistic care ability among oncology nurses, analyze the latent profiles of humanistic care ability and the influencing factors of different profiles.Methods:From December 2022 to March 2023, 836 oncology nurses from 10 Class Ⅲ Grade A hospitals in Shandong Province were selected as the subject using convenience sampling. The survey was conducted using the General Information Questionnaire, Caring Ability Inventory, Professional Identity Scale, and Perceived Organizational Support Scale. Latent profile analysis was conducted using three observable indicators of humanistic care ability, and the influencing factors of different latent profiles of humanistic care ability were analyzed through single factor analysis and unordered multiclass Logistic regression.Results:The overall humanistic care ability of oncology nurses was lower than the international norm level. Through the latent profile analysis, there were three latent profiles, namely the care ability risk group, care ability potential group, and care ability advantage group. The care ability advantage group reached a moderate international norm level in terms of care ability, and its influencing factors included gender, being an only child, professional identity, and perceive organizational support, with statistically significant differences (all P<0.05) . Conclusions:There is significant heterogeneity in the humanistic care ability of oncology nurses, and the latent profile is more accurate in analyzing humanistic care ability compared to overall differentiation. Nursing managers can provide personalized interventions based on different latent profile characteristics and influencing factors, so as to achieve balanced and homogeneous development of the overall care ability of oncology nurses.