ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.

OBJECTIVE To prepare berberine/piperine co-loaded self-microemulsion drug delivery system （BBR/PIP- SMEDDS）， evaluate its physicochemical properties， in vitro release and pharmacokinetic characteristics. METHODS The drug loading mass ratio of berberine （BBR） and piperine （PIP） in the preparation was determined by the everted intestinal sac method. The oil-phase， emulsifier and co-emulsifier were determined by solubility detection， compatibility evaluation and pseudo-ternary phase diagram， respectively. The formulation of blank self-microemulsion drug delivery system （SMEDDS） was optimized and verified by central composite design-response surface methodology with the amount of oil-phase and the mass ratio of emulsifier to co-emulsifier as factors， and the comprehensive score of particle size and Zeta potential as response value. According to the optimal prescription， BBR/PIP-SMEDDS was prepared by adding excessive BBR and PIP raw materials under magnetic stirring， and its physicochemical properties， in vitro release behavior and pharmacokinetic characteristics in rats were investigated. RESULTS The drug loading mass ratio of BBR and PIP was 1∶1. The optimal prescription included oil-phase （ethyl oleate） accounted for 18.54%， emulsifier （Tween-80） accounted for 52.16%， and co-emulsifier （polyethylene glycol 400） accounted for 29.30%. Three verification experiments showed that the average particle size of blank SMEDDS was （16.49±0.49） nm； the Zeta potential was （－16.22±0.77） mV； the comprehensive score was 0.97， the relative deviation of which from the predicted value （0.95） was 2.11%. The prepared BBR/PIP-SMEDDS was an oil-in-water microemulsion， which was a golden yellow oily liquid with a spherical shape. The average particle size was （32.90±0.38） nm， and the Zeta potential was （－19.17±0.70） mV. The encapsulation efficiency of BBR was （90.44±0.88）% ， and the drug loading was （10.18±0.17） mg/g. The encapsulation efficiency of PIP was （87.48±1.13）%， and the drug loading was （9.41±0.17） mg/g. BBR/PIP-SMEDDS had good stability at low temperature （4 ℃ ） in the dark， centri-fugation and dilution. The results of in vitro release showed that the cumulative release percentage of BBR in simulated intestinal fluid for 24 h was significantly higher than that of the raw drug after the preparation of SMEDDS. The pharmacokinetic results in rats showed that the peak concentration and area under the drug- concentration time curve （AUC0－）t of BBR/PIP-SMEDDS were 4.61 and 7.07 times higher than those of the raw drug respectively， and the relative bioavailability was 707.484%. CONCLUSIONS BBR/PIP-SMEDDS is successfully prepared， and the in vitro release and bioavailability of the preparation are greatly improved compared with the raw material.

Objective:To evaluate the accuracy of continuous photoplethysmography algorithms for atrial fibrillation diagnosis and atrial fibrillation burden evaluation via wearable devices.Methods:This study was a self-controlled prospective cohort study. A total of 254 consecutive inpatients were recruited from the Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University from September 2022 to November 2022. All participants were required to wear two devices at the same time: (1) an electrocardiogram (ECG) watch for acquisition of photoplethysmography (watch-recorded-photoplethysmography, W-PPG) and electrocardiogram (watch-recorded-electrocardiogram, W-ECG); (2) an ECG patch for acquisition of electrocardiogram (patch-recorded-electrocardiogram, P-ECG). The results were measured in 30 s data segments and individual participants, separately, which were calculated for sensitivity and specificity by comparing them with the results of expert-read ECG according to the receiver operating characteristic curve. Four groups were separated according to the proportion of the atrial fibrillation burden, and the difference of atrial fibrillation burden from algorithm and expert-read ECG was calculated.Results:All 254 subjects completed the study. The mean age of participants was (63.04±11.04) years old, 99 (38.98%) of them were female, and 97 (38.19%) patients had persistent atrial fibrillation. Expert-read ECG results were taken as standard criteria in all calculations. The P-ECG algorithm had a sensitivity of 94.86% (95% CI: 94.81%-94.91%) and a specificity of 99.30% (95% CI: 99.28%-99.31%) when measured in data segments. The W-PPG algorithm had a sensitivity of 96.07% (95% CI: 95.97%-96.18%) and a specificity of 98.62% (95% CI: 98.59%-98.65%). When measured in terms of individual participants, the P-ECG algorithm had a sensitivity of 92.55% (95% CI: 87.57%-95.71%) and a specificity of 96.39% (95% CI: 93.45%-98.09%), while the W-PPG algorithm had a sensitivity of 93.71% (95% CI: 88.75%-96.67%) and a specificity of 89.62% (95% CI: 85.61%-92.65%). When measured in terms of a single acquisition of W-ECG records, the W-ECG algorithm had a sensitivity of 92.04% (95% CI: 88.14%-94.78%) and a specificity of 96.19% (95% CI: 94.35%-97.47%). For atrial fibrillation burden assessment, the difference between the W-PPG analysis results and the expert-read ECG results was less than 2% in all burden distribution intervals. Conclusions:Continuous photoplethysmography algorithm applied to wearable devices to detect atrial fibrillation is a feasible strategy. Taking expert-read ECG results as standard, continuous monitoring of PPG by a smartwatch is highly accurate for atrial fibrillation diagnosis and can also be used to effectively complete atrial fibrillation burden assessment.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

Objective To optimize the extraction process of flavonoids from Plantago asiatica L.rich in plantagoside by response surface methodology,and to explore the protective effect and mechanism of plantain flavonoids on H2O2-damaged L02 cells.Methods The effects of various parameters,including ethanol concentration,extraction temperature and the liquid-solid ratio on the yield of flavonoids from P.asiatica and the transfer rate of plantagoside were studied by single factor experiment.The central composite design(CCD)and response surface methodology(RSM)were employed on this basic to screen the optimized extraction conditions,which yielded the highest extraction rate of flavonoids from P.asiatica and the maximum transfer rate of plantagoside.The protective effect of flavonoids from P.asiatica on H2O2-damaged L02 cells was assessed through the analysis of cell survival rate,apoptosis rate,mitochondrial membrane potential,malondialdehyde(MDA)and glutathione(GSH)levels,oxide dismutase(SOD)concentration,and the expression levels of HO-1,Nrf2,and SOD proteins.Results The results showed that the highest yield of extraction rate of flavonoids from P.asiatica(1.82％)and the maximum transfer rate of plantagoside(35.01％)were achieved under the optimized extraction condition:extraction temperature of 80 ℃,ethanol concentration of 65％and liquid-solid ratio of 15:1.Flavonoids from P.asiatica extracted under these parameters significantly reduced the apoptosis rate(P<0.001)and the degree of mitochondrial membrane potential damage(P<0.001),increased the expressions of SOD and GSH(P<0.001),and reduced the MDA level(P<0.01,P<0.001)in H2O2-damaged L02 cells at concentrations ranging from 25 to 100 μg·mL-1.In addition,100 μg·mL-1 flavonoids from P.asiatica were found to regulate the expressions of HO-1,Nrf2 and SOD in H2O2-damaged L02 cells.These flavonoids decrease the expressions of HO-1 and Nrf2 proteins,while enhance the expression of SOD protein in H2O2-damaged L02 cells(P<0.05,P<0.01).Conclusion The extraction process for flavonoids from P.asiatica,which was optimized using the response surface method,is operationally simple and yields a high transfer rate of the key active component,plantagoside.This approach offers valuable insights for the actual production of flavonoids from P.asiatica.Besides,flavonoids from P.asiatica could reduce oxidative stress level in H2O2-damaged liver cells,which exhibited a certain protective effect on L02 cells against oxidative damage.This study provides a foundational basis for the development and application of flavonoids from P.asiatica as liver-protective health supplements.

Objective:To assess the efficacy of high-flow nasal cannula oxygen therapy for the respiratory support after tracheal extubation under general anesthesia in neonates.Methods:This was a prospective randomized controlled study. Ninety-four neonates undergoing general surgery under general anesthesia with endotracheal intubation and endotracheal tube removal following surgery from December 2022 to November 2023 in the Third Affiliated Hospital of Zhengzhou University were selected and divided into 2 groups ( n=47 each) by the random number table method: conventional oxygen therapy group (group C) and high-flow nasal cannula oxygen therapy group (group H). After the endotracheal tube was removed, group H underwent high-flow nasal cannula oxygen therapy: oxygen flow was 2 L·kg -1·min -1, the concentration and humidity of oxygen were both 100%, and the temperature was 37 ℃. Group C underwent conventional mask ventilation with the oxygen flow rate 5 L/min, oxygen concentration 100%, ventilation frequency about 25-35 times/min. The outcome measures were recorded from the time after extubation to the time before discharge from the operating theatre. The main outcome measures were the minimum SpO 2 and hypoxemia (SpO 2<90%), choking, laryngospasm and asphyxia. The secondary outcome measures were respiratory rate (immediate extubation, immediate discharge), minimum HR, and time to discharge from the operating theatre. Results:Compared with group C, the lowest SpO 2 was significantly increased, the incidence of hypoxemia and respiratory rate immediately after discharge from the operating room was decreased ( P<0.05), and no significant changes were found in the incidence of choking, laryngospasm and asphyxia, the lowest heart rate, respiratory rate immediately after tracheal extubation and time to discharge from the operating theatre in group H( P>0.05). Conclusions:High-flow nasal cannula oxygen therapy can improve oxygenation and significantly reduce the risk of hypoxemia when used for the respiratory support after tracheal extubation under general anesthesia in neonates.

AIM:To investigate the effects of ginkgetin on neurological deficit and angiogenesis induced by cerebral ischemia/reperfusion(I/R)and its underlying mechanism.METHODS:Sixty SD rats were randomly allocated into three groups:sham group,I/R model group,and ginkgetin(40 mg/kg)treatment(I/R+ginkgetin)group,with twenty rats in each group.The middle cerebral artery occlusion/reperfusion(MCAO/R)rat model was employed to simulate cere-bral I/R,and ginkgetin was administered continuously for 7 days following reperfusion.The cerebral infarction volume was quantified using TTC staining.Neuronal density in the ischemic penumbra was assessed through Nissl staining and immu-nohistochemistry for neuron-specific nuclear protein(NeuN).Microvessel density and angiogenesis in the ischemic pen-umbra of each group were analyzed using CD31 labeling and BrdU/von willebrand factor(vWF)double labeling immuno-fluorescence staining.Western blot analysis was performed to determine the levels of heat shock protein 70(HSP70),vas-cular endothelial growth factor(VEGF),and hypoxia inducible factor-1α(HIF-1α)in the ischemic penumbra.RE-SULTS:Compared with the I/R model group,the cerebral infarction volume was significantly reduced in ginkgetin treat-ment group(P<0.01),the number of neurons,the microvessel density,angiogenesis and the expression levels of HIF-1α,VEGF,and HSP70 in the ischemic penumbra were significantly increased(P<0.01).CONCLUSION:Ginkgetin exhibits the potential to augment angiogenesis and facilitate neurological function recovery in MCAO rats,while concur-rently upregulating the expression of HSP70,VEGF,and HIF-1α within the ischemic penumbra.

As a new clinical trial mode,decentralized & digitalized clinical trial(DCT)is based on digital health equipment and uses internet and artificial intelligence technologies to complete the screening,registration,randomization,intervention,evaluation and follow-up of subjects,which is helpful to improve efficiency and reduce trial costs.The DCT mode has been applied to evaluate the treatment and management effects of cardiovascular diseases such as atrial fibrilla-tion,heart failure,coronary heart disease,and hypertension,showing broad development prospects and application space.This article will provide a brief introduction to representative DCT in the global cardiovascular disease field,and look for-ward to the application prospects of this model,providing reference and guidance for accelerating the development of cardio-vascular DCT in China.