ObjectiveTo determine the pharmacodynamic substance basis of Epimedii Folium（EF） and Epimedii Wushanensis Folium（EWF） in promoting osteogenic differentiation， and to establish a method to analyze the material basis of Chinese materia medica based on the correlation between chemical fingerprint and cellular metabolomics. MethodThe chemical fingerprints of 15 batches of EF with 4 species and 3 batches of EWF were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， and partial least squares-discriminant analysis（PLS-DA） was used to analyze the peak areas of chemical fingerprints of samples. The effects of different samples on proliferative activity of MC3T3-E1 osteoblast precursors， as well as the activity of alkaline phosphatase（ALP） in osteoblasts were detected by cell counting kit-8（CCK-8） and enzyme-linked immunosorbent assay（ELISA）. At the same time， UPLC-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to analyze the effects of different samples on the metabolomics of MC3T3-E1 cells， then metabolic peak table of osteogenic differentiation cells was constructed， and pharmacodynamic index mean Y₀ was introduced into the peak table. PLS was used to calculate mean Y₀ of each group， and the mean Y₀ was added to the peak table of chemical fingerprint to construct the correlation between chemical fingerprint and cell metabolome， the pharmacodynamic components of EF and EWF that promote bone differentiation were screened according to variable importance in the projection（VIP） value>1. The pharmacodynamic effects of EF and EWF were evaluated according to the mean Y₀ of each group. ResultThe chemical fingerprints of EF with different origins and EWF were completely separated. Compared with the blank group， the activity of MC3T3-E1 cells in EF and EWF groups was significantly increased， the activity of ALP in the Epimedium brevicornu（Gansu province）， E. koreanum and E. pubescens groups was significantly increased（P<0.05）. The results of cell metabolomics showed that the blank group and the model group had an obvious trend of separation. EF with different origins and EWF had different distance from the model group， indicating that EF with different origins and EWF had different effect on promoting osteogenic differentiation. Chemical fingerprint-cell metabolomics integration analysis screened 9 components closely related to the efficacy of EF and EWF， including diphylloside B， epimedin C， icariin， baohuoside Ⅰ， yinyanghuo B， β-anhydroicaritin， magnoflorine， cryptochlorogenic acid and quercetin. E. koreanum had the strongest effect on promoting osteogenic differentiation. ConclusionThis study determined that the material basis of EF and EWF promoting osteogenic differentiation were mostly flavonoids， alkaloids and organic acids， which provided ideas and methods for the screening of pharmacodynamic components and the prediction of therapeutic effect of Chinese materia medica.

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.

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.

This study was designed to investigate the effect of Sijunzi decoction(SJZD)on the expression of inflammatory factors and autophagic proteins in the hippocampus of senescence-accelerated mouse prone 8(SAMP8)mice and its mechanism.SAMR1 mice were used as control group,and 32 SAMP8 mice were divided into model group,donepezil group,SJZD low and SJZD high dose treatment groups.Y-maze experiment was performed to detect changes in mouse memory function;the expression of NF-κB was detected by immunohistochemistry;the levels of TNF-α,IL-1β,IL-6 were detected by ELISA;the expression of A[3,caspse-1,beclin-1 and LC3-Ⅱproteins in hippocampal tissue were detected by Western blotting.Compared with the control group,the model group mice showed a decrease in total number of entries and alternations,an elevation in the levels of TNF-α,IL-1β,IL-6,Aβ protein and caspse-1 protein,and downregulation in the expression of beclin-1 and LC3-Ⅱ proteins.Both donepezil and SJZD(low-dose group and high-dose group)can reverse these changes in model mice.In conclusion,the mechanism of SJZD in treating Alzheimer's disease may relate to the correction of central hippocampal inflammatory factors and autophagy dysfunction.

ObjectiveTo study the expression changes of Lon protein and mitochondrial dynamics-related protein in the hippocampus of SAMP8 mice and provide a theoretical basis for the treatment of Alzheimer's disease by invigorating the spleen and supplementing Qi. MethodEight 3-month-old SAMR1 mice were used as the normal group， and 32 3-month-old SAPM8 mice were divided into model group， western medicine group （0.013 g·kg^-1）， low-dose Si Junziwan group （3.24 g·kg^-1）， and high-dose Si Junziwan group （12.56 g·kg^-1）， with 8 mice in each group. The western medicine group was gavaged with donepezil， and the Si Junziwan low- and high-dose groups were gavaged with Si Junziwan for 30 days. The positioning navigation experiment of the water maze was started on the 25^th day， and the space exploration experiment of the water maze was started on the 30^th day. On the 30^th day， the protein expression of mitofusin 2 （MFN2） was detected by immunohistochemistry， the expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK） was detected by enzyme-linked immunosorbent assay （ELISA）， the content of ATP was detected by colorimetry， the microstructure of neuron mitochondria was detected by electron microscope， and the expressions of Aβ protein， Lon protein， dynamin-related protein 1 （DRP1） protein， and MFN1 protein were detected by Western blot. ResultAs compared with the normal group， the latency escape period increased， the number of crossings decreased， the expression of AMPK increased， and the content of ATP decreased in the model group. The expressions of Aβ protein and DRP1 protein increased （P<0.01）， whereas the expressions of Lon protein， MFN1 protein decreased in the model group （P<0.05，P<0.01）， and MFN2 protein decreased. The vacuolation of mitochondria increased and the cristae broke in the model group. As compared with model group， the time of the latent escape period decreased （P<0.01）， and the number of crossings increased in the low-dose and high-dose Si Junziwan groups （P<0.05）. The expression of AMPK （P<0.01） decreased， the content of ATP increased （P<0.01）， the expression of Aβ and DRP1 protein decreased （P<0.05， P<0.01）， and the expression of MFN1 protein was up-regulated （P<0.05） in high-dose Si Junziwan groups. The vacuolation was more obvious in the low-dose Si Junziwan group， whereas the vacuolation was restored and the ridge was clear in the high-dose Si Junziwan group. ConclusionSi Junziwan treats Alzheimer's disease by up-regulating the protein expression of Lon， correcting the disorder of mitochondrial division and fusion protein， and changing the memory function of SAMP8 mice.

Objective:To investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF).Methods:This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality.Results:The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality ( HR=1.28, 95% CI 1.01-1.61, P=0.038), cardiovascular mortality ( HR=1.48,95% CI 1.10-2.00, P=0.010), cardiovascular hospitalization ( HR=1.67,95% CI 1.35-2.07, P=0.008) and the composite endpoints ( HR=2.02,95% CI 1.71-2.38, P<0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality ( HR=1.44,95% CI 1.05-1.98, P=0.025), cardiovascular hospitalization ( HR=1.44,95% CI 1.09-1.90, P=0.010) and the composite endpoints ( HR=1.37, 95% CI 1.01-1.70, P=0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality ( HR=2.56,95% CI 1.44-4.54, P=0.001). Conclusion:Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.

Objective:To analyze the epidemiological characteristics of human brucellosis (HB), evolution and origin feature of Brucella strains in Tongliao city, Inner Mongolia Autonomous Region during 2004-2018, and to provide evidence for strategy development against the disease. Methods:Data from the reports on HB in Tongliao during 2004-2018 were extracted from the China Information System for Disease Control and Prevention before being analyzed with software Excel 2016. Epidemiologic feature was described, using the number of cases, constituent ratio and related rates. Conventional biotypes methods were used for identification of species/biovars strains while species of six Brucella strains were further verified by AMOS-PCR. Cluster analyze on six Brucella strains were performed with Bio-Numerics 5.0 software and for examining and revealing the genetic characteristics of the related strains. Results:During 2004-2018, a total of 16 704 HB cases were reported, with the incidence rate as 35.41/100 000. The incidence rates appeared as 110.51/100 000 in Jarud Banner and 67.84/100 000 in Kulun flag, which were both higher than the other areas. Most of the cases were reported in the 40 -54 year olds, which accounted for 48.75% (8 143/16 704). The number of HB in farmers appeared as 14 873, which counted for 89.04% (14 873/16 704) of all the cases. Male to female ratio of incidence was 2.40∶1. Most of the reported cases appeared between March to May, which accounted for 56.30% (9 405/16 704). Peak of the disease was seen in April. Using the conventional identification method, results showed that the available six strains all belonged to B. melitensis, including three of them as B. melitensis bv.1 and others three strains as B. melitensis bv. 3. Results from the amplified AMOS-PCR showed that all the strains were B. melitensis. The six strains clustered in two MLVA-11 genotypes (111 and 116) and all belonged to the Eastern Mediterranean lineage. Based on the MLVA-16 cluster analysis, results suggested that strains from this study were having close genetic relationship with B. melitensis strains that were from Jilin and Heilongjiang provinces. Conclusions:Human brucellosis identified in Tongliao area was with greater risk in spreading the disease to the vicinity. Our findings indicated that the programs on detection and control of the disease should be strengthened.

Objective: To retrospectively analyze the potential correlation between cardiac magnetic resonance (CMR) imaging and clinical features and idiopathic arrhythmia in patients with straight back syndrome (SBS). Methods: Patients receiving CMR imaging examination from April 2015 to March 2016 at our department (n=1 432) were screened, 76 patients met the diagnosis criteria of flat chest (anteroposterior diameter/transthoracic diameter (APD/TTD) ratio<0.37 at the T8 vertebra). After excluding 33 patients with structural heart disease, 43 SBS patients were divided into two groups: SBS without obvious morphological change in the heart (group A, n=19) and SBS with morphological change of the heart (group B, n=24). CMR images were analyzed, focusing the heart morphological changes induced by SBS. The clinical data were collected to comprehensively analyze the medical history, electrocardiogram and electrophysiological examination in order to observe the relationship between SBS induced heart morphological change and the arrhythmia type and origin. Results: There were 21 male patients in this cohort, mean age was (28.5±11.5) years (13-58 years). APD/TTD ratio was similar between the two groups (0.30±0.03 vs. 0.29±0.04, P>0.05). LVEF tended to be lower in group B than in group A ((47.48±12.77)%vs. (59.31±9.04)%, P>0.05) . In group B, there were 15 patients with left ventricular enlargement, 2 with left ventricular wall thickening, 5 with uncoordinated ventricular wall motion, 5 with tricuspid regurgitation, 3 with mitral regurgitation, 2 with myocardial fibrosis, 5 with increased trabecular and 16 with decreased left ventricular function. Direct compression sign of right ventricle (disappeared precordial fat tissue space, secondary right atria enlargement and tricuspid regurgitation) and left atria (with or without secondary left ventricular enlargement and mitral regurgitation) were evidenced in patients of group B. CMR revealed that the arrhythmia origin corresponded the compression site of the heart in 8 cases (42.1%) in group A and 13 cases (54.2%) in group B, not corresponded to the compression site in 6 patients (31.6%) in group A and in 7 patients (29.2%) in group B, not attributable in 5 patients (26.3%) in group A and 4 patients (16.7%) in group B. The percent of arrhythmia origin corresponded the compression site of the heart tended to be higher in group B as compared to group A (P>0.05). Conclusion SBS can induce changes of cardiac morphology and cardiac function. SBS induced cardiac compression is linked with the development of arrhythmias and might be one of the reasons of arrhythmias in these patients.

Objective To evaluate the diffuse myocardial fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF) by cardiac MR (CMR) T1 mapping methods.Methods Totally 60 subjects (30 paroxysmal AF patients and 30 persistent AF patients) and 59 normal control underwent MR cardiac cine,late gadolinium enhancement,and LV T1 mapping.For T1 mapping,modified Look-Locker inversion recovery sequence was used.Compared with control,pre-contrast ventricular T1 times were quantified and extracellular volume (ECV) was calculated.Results All subjects completed the CMR exam,no myocardial delay enhanced lesion was found.Pre-contrast ventricular T1 time in healthy controls was lower than that in patients with persistent and paroxysmal AF,and the pre-comrast ventricular T1 time in persistent AF patients was higher than that of paroxysmal AF patients (all P＜0.05).The mean LV myocardial ECV had no statistical difference between healthy controls and paroxysmal AF patients (P＞ 0.05),while lower than persistent AF patients (P ＜ 0.05).The mean LV myocardial ECV in patients with persistent AF was larger than that in patients with paroxysmal AF (P＜0.05).LV functional indexes were positive correlated with pre-contrast ventricular T1 time and ECV in patients with AF (all P＜0.05).Conclusion There is LV myocardial fibrosis in patients with AF,and the degree in patients with persistent AF is more severe than that in patients with paroxysmal AF.