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.

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:To explore the relationship between plasma big endothelin-1(Big ET-1)level and left ventricular(LV)remodeling assessed by cardiac magnetic resonance(CMR)in patients with hypertrophic obstructive cardiomyopathy(HOCM).Methods:A total of 180 consecutive HOCM patients were enrolled from November 2013 to July 2015 in Fuwai Hospital,Chinese Academy of Medical Sciences.The baseline characteristics of the patients were collected and the plasma Big ET-1 levels were measured.According to LV remodeling index(LVRI),the patients were divided into severe remodeling group(LVRI>1.3 g/ml,n=119)and mild remodeling group(LVRI≤1.3 g/ml,n=61).The Pearson correlation analysis and multivariate logistic regression analysis were conducted to assess the correlations between plasma Big ET-1 level and indicators of LV remodeling.Results:Compared to the mild remodeling group,the plasma Big ET-1 level([0.84±0.30]pmol/L vs.[0.41±0.19]pmol/L),LVRI([1.7±0.3]g/ml vs.[1.1±0.1]g/ml),the extent of late gadolinium enhancement(LGE)([16.8±8.9]g vs.[7.0±6.6]g)were significantly higher in the severe remodeling group(all P<0.001).Pearson correlation analysis revealed that in patients with HOCM,plasma Big ET-1 level were positively correlated with left atrial anteroposterior diameter,interventricular septal thickness(IVS),LV mass(LVM),LVRI,LGE and LV outflow tract(LVOT)gradient and negatively correlated with LV ejection fraction(all P<0.05).Multivariate logistic regression analysis showed that LVM(OR=1.037,95% CI:1.019-1.056,P<0.001)and plasm Big ET-1 level(OR=11.461,95% CI:2.264-58.014,P=0.003)were the independent determinants for severe LV remodeling in HOCM patients.Conclusions:Among patients with HOCM,the plasma Big ET-1 level are markedly higher in those with severe LV remodeling and are positively associated with left atrial anteroposterior diameter,IVS,LVRI,LVM,LVOT gradient and LGE.Elevated Big ET-1 level and LVM are independent determinants of severe LV remodeling in HOCM patients.

BACKGROUND:The pathogenesis of osteoporosis is closely related to the immune system.A comprehensive and in-depth study of the relationship between immunity and osteoporosis is crucial for understanding and treating the disease.OBJECTIVE:To investigate the role of immune cells in osteoporosis using single-cell sequencing technology.METHODS:Femoral head tissue samples from osteoporosis and non-osteoporosis patients were downloaded from GEO database and analyzed using single-cell sequencing.Data analysis,including cell clustering,functional enrichment,pseudotime trajectory,and cell interaction analyses,was performed using R4.3.0 and software packages such as Seurat v.4.3,monocle(2.28.0),and CellChat.The femoral head tissues of patients with femoral neck fracture who underwent artificial hip replacement surgery were obtained,including two cases of osteoporosis patients and two cases of non-osteoporosis patients.Immunohistochemical staining was used to detect the protein expression of CCL13 and CCL18.qPCR was used to detect the immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA expression.Western blot was used to detect the protein expression of receptor-type tyrosine protein phosphatase C,CD22,and CD99.RESULTS AND CONCLUSION:Transcriptomic analysis identified 10 cell clusters,including osteoclasts,myeloid cells,T cells,osteoblasts,macrophages,monocytes,erythrocytes,B cells,bone marrow mesenchymal stem cells,and mast cells.There was an increase in the ratio of osteoclasts to T cells and a decrease in the ratio of osteoblasts to B cells in the femoral head tissue of the osteoporosis group.Among the B-cell subpopulations,the proportion of B-cells of taxa 1,3(BC1,BC3)in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,and the proportion of B-cells of taxa 2(BC2)was less than that of the non-osteoporosis group.BC1 was enriched significantly for labels such as regulation of adaptive immune response,somatic recombination of immune receptors,and modulation of lymphocyte-mediated immunity,while BC3 was enriched significantly for labels such as regulation of immunoglobulin production,response to type Ⅱ interferon,apoptotic processes involving cysteine endopeptidases,and cytotoxicity.The communication intensity between B-cell subtype BC1 and osteoblasts in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,while the communication intensity between BC3 and BC1 was also increased.The communication between BC3 and BC1 was significantly enriched in the CD22-receptor-type tyrosine protein phosphatase C pathway;the communication between BC1 and osteoblasts was mainly enriched in the CD99-CD99 pathway;and the communication between BC3 and osteoblasts was also highly enriched in the CD99-CD99 pathway.Protein expression of CCL13,CCL18,receptor-type tyrosine protein phosphatase C,CD22,CD99,immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA were higher in femoral tissues of the osteoporosis group than those of the non-osteoporosis group(P＜0.05).To conclude,specific B cell subpopulations can influence the differentiation and apoptosis of osteoblasts in the femoral tissue of osteoporosis patients.

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.

Objective:To investigate the association between frailty and prognosis of elderly patients in the emergency department, and to validate frailty screening tools suitable for the emergency department.Methods:This was a prospective cohort study. Clinical data of elderly patients over 60 years old treated in the emergency department of Beijing Bo'Ai Hospital from January to December 2021 were collected. The Frailty Screening Questionnaire (FSQ), FRAIL Scale (FRAIL) and Clinical Frailty Scale (CFS) were used to score patients, and patients were divided into frail or non-frail group according to the criteria of the above three scales. Twelve-month all-cause mortality was the primary endpoint, dependence and re-admission to the emergency department within 12 months were secondary outcomes. Receiver operating characteristic curves were used to evaluate the ability of the FSQ, FRAIL and CFS scores to predict the primary and secondary endpoints, and the areas under the curve (AUC) were calculated and compared. Survival analysis was performed using Cox hazard proportional regression model, and relative risk was expressed as hazard ratio ( HR) and 95% CI. Results:A total of 406 patients were included in the study. The AUCs (95% CI) of FSQ, FRAIL and CFS scores for predicting 12-month all-cause mortality were 0.879 (0.844-0.909), 0.838 (0.798-0.872), 0.906 (0.873-0.933), respectively (all P<0.001). The AUCs of 3 scores for predicting secondary endpoints ranged from 0.820 to 0.889 (all P<0.001). Pairwise comparisons of the AUCs showed that the CFS was superior to one or both of the other frailty screening scales in predicting 12-month all-cause mortality and dependence except for re-admission to emergency room within 12 months after discharge (all P<0.05). Cox regression analysis revealed that, after adjusting for sex, age, body mass index and comorbidities, frailty as defined by the FSQ, FRAIL, and CFS scales was independently associated with 12-month all-cause mortality, with the HRadj of 3.267 (95% CI: 2.406-4.435), 2.465 (95% CI: 1.819-3.341), 3.523 (95% CI: 2.648-4.687), respectively (all P<0.001). Conclusions:FSQ, FRAIL and CFS scores can predict adverse outcomes, the CFS is a practical frailty screening tool in the emergency department, and frailty screening can improve the risk stratification of older patients.

Objective:To develop and validate a prediction model by combining clinical data and biomarkers to evaluate the probability of frailty among older emergency patients.Methods:A cross-sectional study was conducted. From January 2021 to December 2021, patients aged 60 years and older admitted to the emergency department of China Rehabilitation Research Center were enrolled. Data of patient's clinical information were collected. The patients were divided into frail group and non-frail group according to the Fried's frailty phenotype and clinical data were compared between the two groups. LASSO regression was used to deal with dimension reduction and multivariate logistic regression was employed to construct a prediction model based on variables selected by the LASSO regression. Nomogram was used to visualize the prediction model. The area under the receiver operating characteristic curve, calibration curve, decision curve analysis and bootstrap were used to evaluate the discrimination, calibration, clinical applicability, and internal validity of the model respectively.Results:A total of 348 patients were enrolled, and the incidence of frailty was 53.74% (187/348). Education, coronary heart disease, chronic obstructive pulmonary disease, albumin, fibrinogen, N-terminal pro-brain natriuretic peptide, decreased creatinine, and underweight were independent predictors for frailty in older emergency patients ( P < 0.05). A nomogram model was built based on the above predictors and the model showed good discrimination, calibration and clinical applicability. Conclusions:The study utilized objective clinical data and biomarkers to establish a predictive model for the occurrence of frailty in elderly emergency department patients. This model aids in risk stratification and targeted intervention for elderly emergency patients, thereby improving patient outcomes.

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.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.