Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

Objectives:The study assessed the relationship between atherogenic index of plasma(AIP)and the rapid progression of coronary non-target lesions.Methods:A total of 1 247 patients with coronary artery disease who underwent two coronary angiography examinations at Fuwai Hospital,Chinese Academy of Medical Sciences between January 2010 and September 2014 were enrolled in this retrospective study.The AIP is defined as the base 10 logarithm of the ratio of the concentrations of triglyceride to high-density lipoprotein cholesterol.Patients were divided into the high AIP group(n=623)and the low AIP group(n=624)based on the median value of AIP.Lesion rapid progression is defined as an increase of more than 10%in the lumen stenosis of the lesion with a stenosis rate of more than 50%,or an increase of more than 30%in the lumen stenosis rate of the lesion with a stenosis rate of less than 50%,or a progression to total occlusion within 2 years.Results:Median AIP was 0.39(0.23-0.56)in this patient cohort.Rapid progression of non-target lesions occurred in 65(5.21%),including 42(6.74%)in the high AIP group.The Kaplan-Meier curve showed that the cumulative incidence of rapid progression of non-target lesions was higher in the high AIP group than in the low AIP group(HR=1.751,95%CI:1.053-2.912,log-rank P=0.028).In univariate cox analysis,the AIP and high AIP correlated with rapid progression of non-target lesions.After multivariate adjustment,AIP was an independent risk factor for rapid progression of non-target lesions(adjusted HR=2.731,95%CI:1.090-6.844,P=0.032).Conclusions:AIP is an independent risk factor for rapid progression of non-target lesions.AIP should be considered as a biomarker for estimating the risk of cardiovascular disease,along with other traditional risk factors.

Objectives:The aim of this study was to investigate the value of assessing Selvester QRS score in evaluating myocardial fibrosis in hypertrophic cardiomyopathy(HCM)patients.Methods:A total of consecutive 149 patients with HCM,who were admitted in Fuwai Hospital from October 2008 to September 2013,were enrolled in this study.Qualitative and quantitative analyses of myocardial fibrosis were conducted based on late gadolinium enhancement(LGE)derived from enhanced cardiac magnetic resonance imaging(CMR).According to the qualitative analysis of myocardial fibrosis by CMR-LGE,the patients were divided into the LGE-negative group(n=46)and the LGE-positive group(n=103).Standard 12-lead electrocardiogram examination was performed and the Selvester QRS score was calculated.Multivariate binary Logistic regression analysis was used to analyze the predictive factors of positive LGE,and the correlation analysis between the Selvester QRS score and the LGE score was also performed.Results:Compared with the LGE-negative group,the proportion of patients with a family history of HCM(12.8%vs.28.2%),the proportion of patients with a positive Selvester QRS score(65.2%vs.83.5%)and the Selvester QRS score([1.65±1.81]points vs.[5.71±3.80]points)were higher,the maximum thickness of the left ventricular wall([20.5±3.2]mm vs.[24.5±5.0]mm)and the percentage of left ventricular myocardial scar area([5.0±5.5]%vs.[17.1±11.4]%)were larger in the LGE-positive group(all P<0.05).Multivariate binary logistic regression analysis showed that the Selvester QRS score(OR=1.429,95%CI:1.128-1.802,P=0.003)and the maximum left ventricular wall thickness(OR=1.257,95%CI:1.029-1.537,P=0.025)were independent predictors of positive LGE.Pearson correlation analysis showed that in all HCM patients,the Selvester QRS score was positively correlated with the LGE score(r=0.682,P<0.001),and the percentage of left ventricular myocardial scar area was positively correlated with the percentage of enhanced area to the total mass of left ventricular myocardium(LGE%)(r=0.682,P<0.001);In the LGE positive group,the Selvester QRS score was positively correlated with the LGE score(r=0.569,P<0.001).Receiver operating characteristic(ROC)curve analysis showed that the optimal cut-off values of Selvester QRS score and maximum left ventricular wall thickness for predicting positive LGE were≥3.5 points and≥21 mm,respectively.Conclusions:In HCM patients,the Selvester QRS score is significantly associated with myocardial fibrosis,and the total score≥3.5 serves as a good predictive cutoffvalue for identifying the presence of LGE.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Objectives:The aim of this study was to investigate the value of assessing Selvester QRS score in evaluating myocardial fibrosis in hypertrophic cardiomyopathy(HCM)patients.Methods:A total of consecutive 149 patients with HCM,who were admitted in Fuwai Hospital from October 2008 to September 2013,were enrolled in this study.Qualitative and quantitative analyses of myocardial fibrosis were conducted based on late gadolinium enhancement(LGE)derived from enhanced cardiac magnetic resonance imaging(CMR).According to the qualitative analysis of myocardial fibrosis by CMR-LGE,the patients were divided into the LGE-negative group(n=46)and the LGE-positive group(n=103).Standard 12-lead electrocardiogram examination was performed and the Selvester QRS score was calculated.Multivariate binary Logistic regression analysis was used to analyze the predictive factors of positive LGE,and the correlation analysis between the Selvester QRS score and the LGE score was also performed.Results:Compared with the LGE-negative group,the proportion of patients with a family history of HCM(12.8%vs.28.2%),the proportion of patients with a positive Selvester QRS score(65.2%vs.83.5%)and the Selvester QRS score([1.65±1.81]points vs.[5.71±3.80]points)were higher,the maximum thickness of the left ventricular wall([20.5±3.2]mm vs.[24.5±5.0]mm)and the percentage of left ventricular myocardial scar area([5.0±5.5]%vs.[17.1±11.4]%)were larger in the LGE-positive group(all P<0.05).Multivariate binary logistic regression analysis showed that the Selvester QRS score(OR=1.429,95%CI:1.128-1.802,P=0.003)and the maximum left ventricular wall thickness(OR=1.257,95%CI:1.029-1.537,P=0.025)were independent predictors of positive LGE.Pearson correlation analysis showed that in all HCM patients,the Selvester QRS score was positively correlated with the LGE score(r=0.682,P<0.001),and the percentage of left ventricular myocardial scar area was positively correlated with the percentage of enhanced area to the total mass of left ventricular myocardium(LGE%)(r=0.682,P<0.001);In the LGE positive group,the Selvester QRS score was positively correlated with the LGE score(r=0.569,P<0.001).Receiver operating characteristic(ROC)curve analysis showed that the optimal cut-off values of Selvester QRS score and maximum left ventricular wall thickness for predicting positive LGE were≥3.5 points and≥21 mm,respectively.Conclusions:In HCM patients,the Selvester QRS score is significantly associated with myocardial fibrosis,and the total score≥3.5 serves as a good predictive cutoffvalue for identifying the presence of LGE.

Pannexin 1(PANX1)interacts with purinergic receptors through regulating immune responses,relea-sing adenosine triphosphate(ATP),and the NLRP3/caspase-1/interleukin(IL)-1β signaling pathway,then influ-ences the activation of immune cells and promotes the production of reactive oxygen species(ROS),thus causing in-flammation and tissue damage which exacerbates infection.This research group has synthesized new polypeptides named QE20 and EE20,which can specifically inhibit the opening of PANX1 channels under inflammatory stimula-tion,offering advantages such as reducing cellular ATP release,inhibiting inflammatory factor secretion,and pre-venting hepatocyte pyroptosis,et al.This review summarizes the roles and mechanisms of PANX1 in various infec-tious diseases,and predicts the feasibility of PANX1 as a potential therapeutic target in the future.

Objectives:The study assessed the relationship between atherogenic index of plasma(AIP)and the rapid progression of coronary non-target lesions.Methods:A total of 1 247 patients with coronary artery disease who underwent two coronary angiography examinations at Fuwai Hospital,Chinese Academy of Medical Sciences between January 2010 and September 2014 were enrolled in this retrospective study.The AIP is defined as the base 10 logarithm of the ratio of the concentrations of triglyceride to high-density lipoprotein cholesterol.Patients were divided into the high AIP group(n=623)and the low AIP group(n=624)based on the median value of AIP.Lesion rapid progression is defined as an increase of more than 10%in the lumen stenosis of the lesion with a stenosis rate of more than 50%,or an increase of more than 30%in the lumen stenosis rate of the lesion with a stenosis rate of less than 50%,or a progression to total occlusion within 2 years.Results:Median AIP was 0.39(0.23-0.56)in this patient cohort.Rapid progression of non-target lesions occurred in 65(5.21%),including 42(6.74%)in the high AIP group.The Kaplan-Meier curve showed that the cumulative incidence of rapid progression of non-target lesions was higher in the high AIP group than in the low AIP group(HR=1.751,95%CI:1.053-2.912,log-rank P=0.028).In univariate cox analysis,the AIP and high AIP correlated with rapid progression of non-target lesions.After multivariate adjustment,AIP was an independent risk factor for rapid progression of non-target lesions(adjusted HR=2.731,95%CI:1.090-6.844,P=0.032).Conclusions:AIP is an independent risk factor for rapid progression of non-target lesions.AIP should be considered as a biomarker for estimating the risk of cardiovascular disease,along with other traditional risk factors.

Pannexin 1(PANX1)interacts with purinergic receptors through regulating immune responses,relea-sing adenosine triphosphate(ATP),and the NLRP3/caspase-1/interleukin(IL)-1β signaling pathway,then influ-ences the activation of immune cells and promotes the production of reactive oxygen species(ROS),thus causing in-flammation and tissue damage which exacerbates infection.This research group has synthesized new polypeptides named QE20 and EE20,which can specifically inhibit the opening of PANX1 channels under inflammatory stimula-tion,offering advantages such as reducing cellular ATP release,inhibiting inflammatory factor secretion,and pre-venting hepatocyte pyroptosis,et al.This review summarizes the roles and mechanisms of PANX1 in various infec-tious diseases,and predicts the feasibility of PANX1 as a potential therapeutic target in the future.

Objectives:To evaluate the efficacy and safety of drug-coated balloon in the treatment of de novo coronary chronic occlusive lesions. Methods:Consecutive patients with de novo coronary chronic occlusive lesions treated with drug-coated balloons only were included in this study.The general information,medical history,and surgical information of the patients were recorded,and major adverse cardiovascular events(MACE,including cardiac death,myocardial infarction,and target vessel revascularization)were recorded by telephone or outpatient follow-up. Results:A total of 160 patients were included.There were 26 ostial lesions(16.3%),42 bifurcated lesions(26.3%),117 diffuse lesions(73.1%),and 87 calcified lesions(54.4%).The reference vessel diameter was(2.3±0.4)mm.During hospitalization,there were no acute myocardial infarction,cardiac death,target lesion revascularization,or acute coronary thrombosis.Cardiac death occurred in 1 case and target vessel revascularization occurred in 6 cases during follow-up.The MACE rate is 4.4%. Conclusions:Drug balloon therapy for de novo coronary chronic occlusive lesions is safe and effective,and the prognosis is satisfactory.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).