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 influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial internal carotid artery(ICA)stenosis and to construct a nomogram prediction model.Methods This study retrospectively and consecutively enrolled patients diagnosed with unilateral moderate-to-severe extracranial ICA stenosis and exhibited indications for carotid endarterectomy(CEA)hospitalized in the Department of Neurosurgery at the First Affiliated Hospital of Soochow University,between August 2019 and September 2024.The patients were divided into a stroke group and a non-stroke group,based on their clinical presentation and head MRI results.Baseline characteristics and clinical data including age,sex,body mass index,blood pressure(systolic and diastolic pressure[＜140 mmHg,140-＜160 mmHg,≥160 mmHg]),hypertension,diabetes,smoking and alcohol consumption history,use of statin and antiplatelet medication,fasting blood glucose,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),total cholesterol(TC)were collected and ratios between LDL-C/HDL-C,TG/HDL-C,non-HDL-C(calculated according to equation:non-HDL-C=TC-HDL-C),and non-HDL-C/HDL-C(nHHR)were calculated based on aforementioned data.The clinical and baseline data were then compared between two groups.Imaging data included side of carotid artery stenosis(identified through neck vascular ultrasound,CT angiography and/or DSA),degree of carotid stenosis(with 50％-69％categorized as moderate stenosis,and,70％-99％as severe stenosis),plaque echogenicity(predominantly low,medium or high),plaque calcification(surface and basal calcification),plaque ulceration(exists or not),bilateral middle cerebral artery(MCA)hemodynamic parameters measured by transcranial Doppler ultrasound(including,mean flow velocity[Vm],peak systolic velocity[Vs],end-diastolic velocity[Vd]),and the pulsatility index(PI,calculated via formula:PI=[Vs-Vd]/Vm).The hemodynamic parameter differences(△Vm,△Vs,△Vd,△PI)between the healthy and affected MCA were calculated.The baseline,clinical and imaging data with P＜0.05 in univariate analysis were included in multivariate Logistic regression analysis using forward stepwise selection to identify influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis,and a nomogram prediction model was then constructed base on the analyzed results.Receiver operating characteristic curves were plotted,and the area under the curve(AUC)was calculated to evaluate the predictive performance of the nomogram.Delong's test was used to compare AUC differences between single indicators and the combined model.Results A total of 166 patients with unilateral moderate-to-severe extracranial ICA stenosis and CEA indication were included.In which,99 patients were in the stroke group and 67 patients were in the non-stroke group.The stroke group had a significantly higher proportion of hypertension patients(78.8％[78/99]vs.59.7％[40/67],P=0.008),higher systolic blood pressure([152±15]mmHg vs.[137±18]mmHg,P＜0.01),higher diastolic blood pressure([84±10]mmHg vs.[80±10]mmHg,P=0.042),higher TG(1.33[0.95,1.77]mmol/L vs.1.10[0.87,1.48]mmol/L,P=0.019),higher TG/HDL-C(1.35[0.97,2.08]vs.1.07[0.81,1.52],P=0.003),and higher nHHR(2.89[2.25,3.61]vs.2.48[1.93,3.27],P=0.027)than the non-stroke group.The HDL-C was significantly lower in the stroke group(0.96[0.80,1.15]mmol/L vs.1.03[0.91,1.16]mmol/L,P=0.014).Statistically significant differences were also observed in the distribution of systolic blood pressure between the groups(P＜0.01).No significant differences were found in other clinical data(all P＞0.05).The proportion of patients with carotid plaque ulceration was higher in the stroke group(35.4％[35/99]vs.16.4％[11/67],P=0.007),while stenosis side,stenosis degree,plaque echogenicity,and plaque calcification type showed no significant differences between the groups(all P＞0.05).△Vm(19[4,32]cm/s vs.10[-3,21]cm/s,P=0.001),△Vs(32[9,55]cm/s vs.24[3,40]cm/s,P=0.005),and △Vd(10[-1,19]cm/s vs.6[-3,12]cm/s,P=0.006)were significantly higher in the stroke group.No significant difference was found in △PI(P=0.076).Multivariate Logistic regression analysis identified high systolic blood pressure(OR,1.063,95％CI 1.036-1.090,P＜0.01),high TG/HDL-C(OR,2.802,95％CI 1.551-5.061,P=0.001),high △Vm(OR,1.032,95％CI 1.010-1.055,P=0.004),and plaque ulceration(OR,2.777,95％CI 1.123-6.871,P=0.027)as independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.Systolic blood pressure,TG/HDL-C,△Vm and plaque ulceration were involved in the construction of a combined predictive model for ischemic stroke in the targeted patient group(with unilateral moderate-to-severe extracranial ICA stenosis).The AUC of the combined prediction model was 0.828(95％CI 0.765-0.892,P＜0.01),which was significantly higher than the predictive efficacy of any single factor(all P＜0.01).Conclusions High systolic blood pressure,high TG/HDL-C ratio,high △Vm,and plaque ulceration are independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.The nomogram prediction model based on these factors demonstrates good predictive value for assessing ischemic stroke risk in this patient population.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

Objective:To explore the impact of lifestyle on TCM constitutions among female medical workers at Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine using questionnaires; To provide references for optimizing their health management.Methods:A cross-sectional study was conducted. A total of 500 female medical workers were randomly selected from Xiyuan Hospital from April to December 2022 to complete the questionnaires. The relationship between lifestyle and constitutions of female medical workers was analyzed.Results:A total of 457 cases completed the questionnaires. Among the 9 constitutions, 102 people (22.32%) had a peaceful constitution, while 355 people (77.68%) had a biased constitution; the top three biased constitutions were qi stagnation constitution 90 people (19.69%), yang deficiency constitution 83 people (18.16%), and phlegm-dampness constitution 56 people (12.25%). The factors that influenced physical constitutions according to the severity of lifestyle were: sleep, diet, mood, exercise, labor, environment, children, and education.Conclusions:Female medical workers have a high proportion of biased constitution, and the main types of biased constitution are qi stagnation constitution, yang deficiency constitution, and phlegm-dampness constitution. According to the existing biased constitution, targeted adjustments and interventions are carried out, and it is of great significance to protect and care for the health of female medical workers from the concept of preventive treatment of diseases with TCM.

Atherosclerosis is the main pathological basis of coronary heart disease,and is thus of great importance in terms of the prevention and treatment of coronary heart disease.Neuropilin-1(NRP1),a member of the neuropilin receptor family,is closely associated with various growth factors,including vascular endothelial growth factor(VEGF)and transforming growth factor-β(TGF-β).NRP1 influences the progression of atherosclerosis through its crucial roles in angiogenesis and inflammatory responses,and sensing of wall shear stress on the vascular endothelium.This review thus explores the mechanisms underlying the role of NRP1 in atherosclerosis and the development of NRP1-targeted therapeutic strategies,to provide new insights into the diagnosis and treatment of atherosclerosis.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

Objective To explore the influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial internal carotid artery(ICA)stenosis and to construct a nomogram prediction model.Methods This study retrospectively and consecutively enrolled patients diagnosed with unilateral moderate-to-severe extracranial ICA stenosis and exhibited indications for carotid endarterectomy(CEA)hospitalized in the Department of Neurosurgery at the First Affiliated Hospital of Soochow University,between August 2019 and September 2024.The patients were divided into a stroke group and a non-stroke group,based on their clinical presentation and head MRI results.Baseline characteristics and clinical data including age,sex,body mass index,blood pressure(systolic and diastolic pressure[＜140 mmHg,140-＜160 mmHg,≥160 mmHg]),hypertension,diabetes,smoking and alcohol consumption history,use of statin and antiplatelet medication,fasting blood glucose,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),total cholesterol(TC)were collected and ratios between LDL-C/HDL-C,TG/HDL-C,non-HDL-C(calculated according to equation:non-HDL-C=TC-HDL-C),and non-HDL-C/HDL-C(nHHR)were calculated based on aforementioned data.The clinical and baseline data were then compared between two groups.Imaging data included side of carotid artery stenosis(identified through neck vascular ultrasound,CT angiography and/or DSA),degree of carotid stenosis(with 50％-69％categorized as moderate stenosis,and,70％-99％as severe stenosis),plaque echogenicity(predominantly low,medium or high),plaque calcification(surface and basal calcification),plaque ulceration(exists or not),bilateral middle cerebral artery(MCA)hemodynamic parameters measured by transcranial Doppler ultrasound(including,mean flow velocity[Vm],peak systolic velocity[Vs],end-diastolic velocity[Vd]),and the pulsatility index(PI,calculated via formula:PI=[Vs-Vd]/Vm).The hemodynamic parameter differences(△Vm,△Vs,△Vd,△PI)between the healthy and affected MCA were calculated.The baseline,clinical and imaging data with P＜0.05 in univariate analysis were included in multivariate Logistic regression analysis using forward stepwise selection to identify influencing factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis,and a nomogram prediction model was then constructed base on the analyzed results.Receiver operating characteristic curves were plotted,and the area under the curve(AUC)was calculated to evaluate the predictive performance of the nomogram.Delong's test was used to compare AUC differences between single indicators and the combined model.Results A total of 166 patients with unilateral moderate-to-severe extracranial ICA stenosis and CEA indication were included.In which,99 patients were in the stroke group and 67 patients were in the non-stroke group.The stroke group had a significantly higher proportion of hypertension patients(78.8％[78/99]vs.59.7％[40/67],P=0.008),higher systolic blood pressure([152±15]mmHg vs.[137±18]mmHg,P＜0.01),higher diastolic blood pressure([84±10]mmHg vs.[80±10]mmHg,P=0.042),higher TG(1.33[0.95,1.77]mmol/L vs.1.10[0.87,1.48]mmol/L,P=0.019),higher TG/HDL-C(1.35[0.97,2.08]vs.1.07[0.81,1.52],P=0.003),and higher nHHR(2.89[2.25,3.61]vs.2.48[1.93,3.27],P=0.027)than the non-stroke group.The HDL-C was significantly lower in the stroke group(0.96[0.80,1.15]mmol/L vs.1.03[0.91,1.16]mmol/L,P=0.014).Statistically significant differences were also observed in the distribution of systolic blood pressure between the groups(P＜0.01).No significant differences were found in other clinical data(all P＞0.05).The proportion of patients with carotid plaque ulceration was higher in the stroke group(35.4％[35/99]vs.16.4％[11/67],P=0.007),while stenosis side,stenosis degree,plaque echogenicity,and plaque calcification type showed no significant differences between the groups(all P＞0.05).△Vm(19[4,32]cm/s vs.10[-3,21]cm/s,P=0.001),△Vs(32[9,55]cm/s vs.24[3,40]cm/s,P=0.005),and △Vd(10[-1,19]cm/s vs.6[-3,12]cm/s,P=0.006)were significantly higher in the stroke group.No significant difference was found in △PI(P=0.076).Multivariate Logistic regression analysis identified high systolic blood pressure(OR,1.063,95％CI 1.036-1.090,P＜0.01),high TG/HDL-C(OR,2.802,95％CI 1.551-5.061,P=0.001),high △Vm(OR,1.032,95％CI 1.010-1.055,P=0.004),and plaque ulceration(OR,2.777,95％CI 1.123-6.871,P=0.027)as independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.Systolic blood pressure,TG/HDL-C,△Vm and plaque ulceration were involved in the construction of a combined predictive model for ischemic stroke in the targeted patient group(with unilateral moderate-to-severe extracranial ICA stenosis).The AUC of the combined prediction model was 0.828(95％CI 0.765-0.892,P＜0.01),which was significantly higher than the predictive efficacy of any single factor(all P＜0.01).Conclusions High systolic blood pressure,high TG/HDL-C ratio,high △Vm,and plaque ulceration are independent risk factors for ischemic stroke in patients with unilateral moderate-to-severe extracranial ICA stenosis.The nomogram prediction model based on these factors demonstrates good predictive value for assessing ischemic stroke risk in this patient population.

Atherosclerosis is the main pathological basis of coronary heart disease,and is thus of great importance in terms of the prevention and treatment of coronary heart disease.Neuropilin-1(NRP1),a member of the neuropilin receptor family,is closely associated with various growth factors,including vascular endothelial growth factor(VEGF)and transforming growth factor-β(TGF-β).NRP1 influences the progression of atherosclerosis through its crucial roles in angiogenesis and inflammatory responses,and sensing of wall shear stress on the vascular endothelium.This review thus explores the mechanisms underlying the role of NRP1 in atherosclerosis and the development of NRP1-targeted therapeutic strategies,to provide new insights into the diagnosis and treatment of atherosclerosis.

Objective To quantitatively analyze and evaluate the content of rehabilitation policy for people with disabilities in China. Methods This study focused on ten national policies of disability rehabilitation issued from 2021 to 2023.It employed text mining techniques to process policy texts and constructed a policy modeling consistency index model for dis-ability rehabilitation policies in China.The relevant policies were evaluated and analyzed quantitatively. Results The disability rehabilitation policies in China were relatively comprehensive in terms of policy transparency,op-erational mechanisms and policy nature.However,there was still a need for optimization in terms of policy per-spectives,target groups,incentive mechanisms,and other aspects. Conclusion The overall quality of disability rehabilitation policy texts at the national level in China is relatively good.There is a need to further enhance the predictability of policy objectives,clarify the responsibilities and division of labor among various departments,and improve policy incentive mechanisms in future policy formulation,which will further refine China's disability rehabilitation policy system and contribute to high-quality develop-ment of the disability cause.

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*