ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

Through consulting herbal medicine， medical books， and local chronicles from past dynasties to modern times， this paper systematically researched Spatholobi Caulis from name， origin， producing areas， harvesting， processing， usage， quality evaluation， functions and indications， providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research， Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning， Yunnan， and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them， K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians， mainly treating rheumatic pain and injuries caused by falls or blows， and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction， which had the functions of promoting blood circulation and replenishing blood， activating meridians and collaterals， and mainly used for treating anemia， irregular menstruation， and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently， the main production area of S. suberectus is Guangxi， while the main production area of K. interior is Yunnan. In the Qing dynasty， the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments， which was usually composed of the juice of it， safflower， angelica， and glutinous rice. But in modern times， Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface， with a higher number indicating better quality. Additionally， the presence of resinous secretions is also considered desirable. Based on the research findings， it is suggested that when developing famous classical formulas containing Spatholobi Caulis， the choice of the primary source should be S. suberectus or K. heteroclita， taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia， adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names， and the functions adjust to promote Qi circulation and relieve pain， disperse blood stasis and unblock collaterals， treating injuries caused by falls and bruises.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of Aconitum carmichaelii was selected as the research object. Its ¹H-¹³C HSQC, ¹H-¹H COSY, HMBC, and NOESY spectra were acquired by US and NUS methods, respectively. By comparing the integral values of NMR signals of three chemical groups in fuziline, it is confirmed that the NUS technique has the advantages of improving the quality of 2D NMR spectra and shortening the acquisition time in structure elucidation of small molecule compounds. In HMBC spectrum, it was further confirmed that NUS technology can improve the quality of the 2D spectra and the signal resolution. This indicates that NUS technology can improve the efficiency and reliability of the structure elucidation of small molecule compounds.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors