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*

A microchannel-based electrochemiluminescence(ECL)sensor was developed for detection of tetracycline(TC)utilizing luminol/H2O2 as ECL reporting system.The low excitation potential of luminol/H2O2 effectively mitigated the impact of clamping voltage,thereby enhancing the detection performance of the microchannel-based ECL sensor.The microchannel modified with TC aptamer selectively recognized and captured target TC.The positively charged TC reduced the surface charge density within the microchannel,thereby increasing the ionic current in the microchannel,leading to change of ECL signal of system.The experimental conditions such as electrolyte concentration,TC-aptamer concentration,and reaction time between TC and TC-aptamer were optimized.Under optimal conditions,the difference of ECL signal in the absence and presence of TC(?ECL)exhibited a good linear relationship with TC concentration in the range from 1.00 ng/mL to 200 ng/mL,with a detection limit as low as 0.69 ng/mL.The sensor had good selectivity and was successfully used in detection of TC in milk samples.

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.

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 investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

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.

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.