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 construct trajectory models of care-seeking patterns for type 2 diabetes mellitus(T2DM)patients,analyze the influencing factors of different trajectories,and explore the fasting blood glucose control levels of T2DM patients with different trajectories.Methods A retrospective cohort study was carried out on 18088 T2DM patients who had health records and been involved in the diabetic management in Community Health Service Center of Minhang District,Shanghai from 2006 to 2009.Starting from Jan 1,2010,participants were followed up until Dec 31,2019,with complete follow-up information.Group-based trajectory modelling(GBTM)was employed to identify and construct the fluctuation trajectory of fasting blood glucose in the patients.Bayesian information criterion(BIC),average posterior probability(AvePP)and other evaluation indicators were used to select the optimum subgroup number model.Then the differences in demographic characteristics,health status,family history,fasting blood glucose,BMI,etc were compared among different categories.Multinational logistic regression model was constructed to explore the influencing factors of different fluctuation trajectories.Cox regression analysis was used to examine the relationship between the long-term trajectories of care-seeking patterns and fasting blood glucose control level.Results Using GBTM analysis,we constructed the optimal Model 4 to categorize 18088 T2DM patients with community health records into five distinct trajectory subgroups:continuous non-attendance group(22.29%),low-level increasing group(15.09%),high-level slowly decreasing group(14.18%),high-level rapidly decreasing group(14.90%),and continuous regular attendance group(33.54%).With the continuous regular attendance group serving as the reference,gender,age,place of residence,baseline comorbidity of hypertension,baseline fasting plasma glucose level,and BMI were found to influence the community attendance trajectories of T2DM patients(P<0.05).After adjusting for confounding factors,Cox regression analysis revealed that compared to the continuous non-attendance group,the low-level increasing group,high-level slowly decreasing group,and continuous regular attendance group had better glycemic control,with HRs of 0.37(95%CI:0.34-0.39),0.72(95%CI:0.67-0.78),and 0.78(95%CI:0.73-0.84),respectively.The glycemic control level in the high-level rapidly decreasing group was comparable,with an HR of 1.06(95%CI:0.99-1.12).Conclusion Based on the optimal model,the community medical treatment trajectories of T2DM patients showed different dynamic characteristics.Factors such as gender,residence,hypertension,and weight loss may influence these varying trajectories.Regular community visits and follow-up may help control blood glucose levels.

Objective To investigate the influencing factors of Mismatch ratio in computed tomography perfusion(CTP)and dif-fusion weighted imaging(DWI)to assess the lesion outcome after treatment in patients with acute ischemic stroke(AIS).Methods Whether there were any differences in clinical and imaging data of AIS patients were analyzed retrospectively between the Mismatch ratio＞1.2 group and the Mismatch ratio≤1.2 group,and between the hemorrhagic transformation group and the non-hemorrhagic transformation group.Results The age of onset and National Institutes of Health Stroke Scale(NIHSS)score of AIS patients in the group with Mismatch ratio＞1.2 were greater than those in the group with Mismatch ratio≤1.2.The Mismatch ratio＞1.2 group had lower incidence of hyperlipidemia,new infarct foci,and higher hypercoagulability,cerebral hemorrhage,as well as large cerebral infarction.The NIHSS score was higher in the hemorrhagic transformation group than the non-hemorrhagic transformation group,and the incidence of large cerebral infarction and digital subtraction angiography(DSA)thrombectomy was higher in the former than in the latter.Multifactorial logistic analysis showed that age,NIHSS score,and hyperlipidemia were independent risk factors for AIS patients with Mismatch ratio＞1.2 and large cerebral infarction was an independent risk factor for hemorrhagic transformation.Conclusion The Mismatch ratio in CTP is correlated with age,NIHSS score,and hyperlipidemia in patients with AIS and large cerebral infarction is correlated with hemorrhagic transformation.

Background::Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level.Methods::Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis.Results::The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking.Conclusion::With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

Objective:To investigate the clinical and imaging characteristics of cervical spine hyperextension injury plus multilevel disco-ligamentous complex (MDLC) injury and the therapeutic effectiveness of their treatment.Methods:A total of 456 patients with cervical hyperextension injury were hospitalized between January 2010 and October 2020 at Department of Orthopaedics, The 909th Hospital, Dongnan Hospital Affiliated to Xiamen University. A retrospective study was conducted to analyze the clinical data of the 43 patients among them who had been diagnosed with MDLC injury and undergone surgical treatment and been fully followed up. They were 37 males and 6 females with an age of (50.6±10.7) years. According to the American Spinal Injury Association (ASIA) grading, there were 1 case of grade A, 8 cases of grade B, 18 cases of grade C, and 16 cases of grade D. The Japanese Orthopaedic Association (JOA) score was (7.9±1.6) points. Anterior cervical decompression, fusion and internal fixation were conducted for 42 patients, and posterior total laminectomy and internal fixation for 1 patient. The clinical and imaging manifestations of the patients, and the consistency between preoperative and intraoperative diagnosis of disco-ligamentous complex (DLC) injury were analyzed. ASIA grading and JOA score were used to assess the outcomes of surgical treatment and comparisons were made between preoperation and postoperation.Results:DLC injury existed at 99 levels (43 cases), with a high incidence at level C 5-6 (30 cases), and high-signal manifestations of cervical cord injury existed at 48 levels, with a high incidence at level C 3-4 (16 cases). Two-segment DLC injury was the most common [74.4% (32/43)], while three-segment DLC injury existed in 9 cases and four-segment DLC injury in 2 cases. There were 21 cases of jumping MDLC injury and 22 cases of continuous MDLC injury. At preoperation, DLC injury was suspected in 10 patients (at 11 levels), of whom 8 (at 9 levels) were diagnosed intraoperatively with DLC injury, and 2 (at 2 levels) were excluded from the DLC injury. All the 43 patients were followed up for (54.7±10.7) months. By the ASIA grading at the last follow-up, 3 cases were grade C, 13 cases grade D, and 27 cases grade E. The JOA score at the last follow-up was (15.1±2.2) points. Both the 2 outcomes showed significant improvements compared with the preoperative values ( P<0.05). Conclusions:The clinical incidence of cervical hyperextension injury combined with MDLC injury is low, but relatively higher in the middle-aged and elderly patients. As the level of DLC injury is often inconsistent with the likely level of cervical spinal cord injury, surgical exploration of the DLC structure with suspected injury can reduce the rate of missed diagnosis and misdiagnosis.

Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.

Objective:This study aims to evaluate the effectiveness and safety of drug coated balloon(DCB)and drug elu-ting stent(DES)during primary percutaneous coronary intervention(PCI)in patients with ST segment elevation myocardi-al infarction(STEMI).Methods:Clinical data of 142 STEMI patients who underwent emergency PCI in our hospital from Jan 2018 to Dec 2021 were retrospectively analyzed.According to intervention strategy,patients were divided into obser-vation group(n=62,DCB therapy)and control group(n=80,DES therapy).Incidence rates of target lesion revascular-ization and major adverse cardiovascular events(MACE)within one week,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd)and incidence rate of slow-flow after PCI,above indexes(except slow-flow),late lumen loss(LLL)and incidence of hemorrhea etc.within nine-month follow-up were compared between two groups.Results:There were no significant difference in postoperative LVEDd,LVEF,incidence rates of slow-flow,target lesion revascularization and MACE within one week between two groups,P＞0.05 all.After nine-month follow-up,there were no significant difference in LLL[0.25(0.16,0.50)mm vs.0.30(0,0.82)mm],incidence rates of target lesion revascularization(6.3％vs.4.8％),MACE(31.7％vs.33.9％)and hemorrhea(8.5％vs.3.2％)be-tween control group and observation group,P＞0.05 all.Conclusion:In patients with ST segment elevation myocardial in-farction undergoing emergency percutaneous coronary intervention,short-and long-term prognosis of drug coated bal-loon are not inferior to those of drug eluting stent,which is safe and effective.

Objective:To analyze the individual and cumulative effects of unhealthy lifestyle on the prevalence of hypertension, diabetes and dyslipidemia in old adults in China, and find out the critical lifestyle in the network.Methods:Based on the baseline data of Yunnan Behavior and Disease Surveillance Cohort in 2021, a total of 16 763 older adults aged ≥60 years were included in our study. The unhealthy lifestyle factors including smoking, drinking, unhealthy eating habit, lower physical activity level, abnormal BMI and abnormal waist circumference. We calculated the unhealthy lifestyle score by using the cumulative exposures of each participant. Multiple logistic regression and mixed graphical models were used to describe the association between unhealthy lifestyle and the prevalence of hypertension, diabetes and dyslipidemia.Results:The prevalence of hypertension, diabetes and dyslipidemia were 57.0%, 11.5% and 37.0%, respectively. Most of the unhealthy lifestyles included in the study were risk factors for hypertension, diabetes and dyslipidemia, and the risks of disease increased with the increase of the unhealthy lifestyle score. The participants with the highest score (score: 6) had significantly higher prevalence of hypertension ( OR=3.99, 95% CI: 1.81-8.80), diabetes ( OR=4.64, 95% CI: 1.64-13.15) and dyslipidemia ( OR=4.26, 95% CI: 2.08-8.73) compared with those with lowest score (score: 0). In the network constructed by mixed graphical model, abnormal waist circumference (bridge strength=0.81) and hypertension (bridge strength=0.55) were vital bridge nodes connecting unhealthy lifestyle and hypertension, diabetes and dyslipidemia. Conclusions:The unhealthy lifestyle score was associated with risks for hypertension, diabetes and dyslipidemia. Abnormal waist circumference was the key factor for chronic diseases in old adults.

In recent years, the research focus on health-related behavior and chronic non-communicable diseases has shifted from the analysis on independent effects of multiple causes on a single outcome to the evaluation the complex relationships between multiple causes and multiple effects. Complex network theory, an important branch of system science, considers the relationships among factors in a network and can reveal how health-related behaviors interact with chronic diseases through a series of complex network models and indicators. This paper summarizes the definition and development of complex network theory and its commonly used models, indicators, and case studies in the field of health-related behavior and chronic disease to promote the application of complex network theory in the field of health and provide reference and tools for future research of the relationship between health-related behavior and chronic disease.

Objective:To explore the association between occupational noise perception and cardiovascular disease (CVD), depression symptoms, as well as their comorbidity in occupational population and provide evidence for the prevention and control of physical and mental illnesses.Methods:A cross-sectional survey design was adopted, based on baseline data in population in 28 prefectures in Sichuan Province and Guizhou Province, and 33 districts (counties) in Chongqing municipality from Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during October to December 2021. A questionnaire survey was conducted to collect information about noise perception, depressive symptoms, and the history of CVD. Latent profile analysis model was used to determine identify noise perception type, and multinomial logistic regression analysis was conducted to explore the relationship between different occupational noise perception types and CVD, depression symptoms and their comorbidity.Results:A total of 30 509 participants were included, the mean age was (36.6±10.5) years, and men accounted for 82.0%. The direct perception of occupational noise, psychological effects and hearing/sleep impact of occupational noise increased the risk for CVD, depressive symptoms, and their comorbidity. By using latent profile analysis, occupational noise perception was classified into four levels: low, medium, high, and very high. As the level of noise perception increased, the association with CVD, depressive symptoms, and their comorbidity increased. In fact, very high level occupational noise perception were found to increase the risk for CVD, depressive symptoms, and their comorbidity by 2.14 (95% CI: 1.73-2.65) times, 8.80 (95% CI: 7.91-9.78) times, and 17.02 (95% CI: 12.78-22.66) times respectively compared with low-level occupational noise perception. Conclusions:Different types of occupational noise perception are associated with CVD and depression symptom, especially in the form of CVD complicated with depression symptom. Furthermore, the intensity of occupational noise in the work environment should be reduced to lower the risk for physical and mental health.