ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Objective To explore the changes of serum angiopoietin-like protein 4(ANGPTL4)and NOD-like receptor protein 3(NLRP3)levels after traumatic brain injury(TBI)and their diagnostic value for sec-ondary massive cerebral infarction.Methods A total of 100 TBI patients admitted to the hospital from Au-gust 2019 to August 2021 were enrolled as the TBI group,meantime,100 healthy people in the hospital were enrolled as the control group.The serum levels of ANGPTL4 and NLRP3 were detected by enzyme-linked im-munosorbent assay(ELISA).The clinical characteristics of TBI patients with and without secondary massive cerebral infarction were compared.Receiver operating characteristic(ROC)curve was applied to analyze the serum levels of ANGPTL4 and NLRP3 on their diagnostic value for TBI patients with secondary massive cere-bral infarction.Multivariate Logistic regression analysis was applied to analyze the factors affecting the occur-rence of secondary massive cerebral infarction in TBI patients.Results The serum ANGPTL4 level in TBI group was lower than that in the control group,and the serum NLRP3 level was higher than that in the con-trol group(P<0.05).There were obvious differences in proportion of brain hernia,proportion of subarach-noid hemorrhage,serum levels of ANGPTL4 and NLRP3 between patients with secondary massive cerebral infarction and patients without secondary massive cerebral infarction(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum ANGPTL4 and NLRP3 in diagnosing secondary massive cere-bral infarction in TBI patients was 0.792 and 0.812 respectively,with sensitivity of 77.80%and 83.30%re-spectively,and specificity of 86.60%and 64.60%respectively.The sensitivity,the specificity and AUC of the combined detection were 83.30%,82.90%and 0.867 respectively.Multivariate Logistic regression analysis showed that serum NLRP3 level was a risk factor for TBI patients with secondary massive cerebral infarction(P<0.05).After treatment,it was found that serum ANGPTL4 level increased and NLRP3 level decreased in TBI patients(P<0.05).Conclusion The serum level of ANGPTL4 in TBI patients decreases,while the level of NLRP3 increases,and the level of ANGPTL4 in the serum of patients with secondary massive cerebral in-farction decreases and the level of NLRP3 increases,both of them are of great significance in the diagnosis of secondary massive cerebral infarction in TBI patients.

Objective To investigate the predictive value of Rotterdam CT score combined with serum soluble cluster of differentiation antigen 40 ligand (sCD40L) and fibulin-5 for prognosis of patients with severe traumatic brain injury (sTBI). Methods A total of 186 sTBI patients were divided into good prognosis group (n=104) and poor prognosis group (n=82). CT images were analyzed and Rotterdam CT scores were obtained; the enzyme-linked immunosorbent assay (ELISA) was used to detect serum sCD40L and fibulin-5 levels on the 1st, 3rd and 7th day of admission; the Spearman analysis was used to assess the correlations of serum sCD40L and fibulin-5 levels on the first day of admission with the Rotterdam CT score and Glasgow Coma Scale (GCS) score; the Multivariate Logistic regression analysis was conducted to explore the risk factors for poor prognosis in sTBI patients; the receiver operating characteristic (ROC) curve was performed to analyze the predictive value of Rotterdam CT score combined with serum sCD40L and fibulin-5 levels on the first day of admission for prognosis of sTBI patients. Results On the 1st, 3rd and 7th day of admission, compared with the good prognosis group, the serum levels of sCD40L and fibulin-5 in the poor prognosis group were significantly elevated (P < 0.05); serum sCD40L and fibulin-5 levels were negatively correlated with GCS scores (r=-0.505, -0.421, P < 0.05) and positively correlated with Rotterdam CT score (r=0.495, 0.397, P < 0.05); sCD40L (OR=2.768, 95%CI, 1.537 to 4.983) and fibulin-5 (OR=2.539, 95%CI, 1.301 to 4.953) were independent risk factors for poor prognosis in sTBI patients (P < 0.001); the area under the curve (AUC) of Rotterdam CT score combined with serum sCD40L and fibulin-5 levels on the first day of admission for predicting poor prognosis in sTBI patients was 0.969 (95%CI, 0.933 to 0.989), with a sensitivity of 86.59% and a specificity of 94.23%; the diagnostic performance of Rotterdam CT score combined with sCD40L and fibulin-5 was superior to that of each individual indicator (Z=4.233, 4.274, 4.433, P < 0.001); the Bootstrap internal validation results showed that the predictive performance curve of the combined prediction model was consistent with the actual clinical occurrence curve. Conclusion Rotterdam CT score combined with serum sCD40L and fibulin-5 has certain predictive value for poor prognosis in sTBI patients.

BACKGROUND: Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population. METHODS: Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately. RESULTS: In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model. CONCLUSIONS In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
Male ; Humans ; Female ; Coronary Artery Disease/genetics* ; Biological Specimen Banks ; East Asian People ; Risk Assessment/methods* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Genome-Wide Association Study

BACKGROUND: Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population. We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults. METHODS: We used data from the China Kadoorie Biobank and included 512,723 participants aged 30 to 79 years. Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline. Multimorbidity patterns were identified using hierarchical cluster analysis. Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality. RESULTS: Overall, 15.8% of participants had multimorbidity. The prevalence of multimorbidity increased with age and was higher in urban than rural participants. Four multimorbidity patterns were identified, including cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), gastrointestinal and hepatorenal multimorbidity (gallstone disease, chronic kidney disease, cirrhosis, peptic ulcer, and cancer), and mental and arthritis multimorbidity (neurasthenia, psychiatric disorder, and rheumatoid arthritis). During a median of 10.8 years of follow-up, 49,371 deaths occurred. Compared with participants without multimorbidity, cardiometabolic multimorbidity (hazard ratios [HR] = 2.20, 95% confidence intervals [CI]: 2.14 - 2.26) and respiratory multimorbidity (HR = 2.13, 95% CI:1.97 - 2.31) demonstrated relatively higher risks of mortality, followed by gastrointestinal and hepatorenal multimorbidity (HR = 1.33, 95% CI:1.22 - 1.46). The mortality risk increased by 36% (HR = 1.36, 95% CI: 1.35 - 1.37) with every additional disease. CONCLUSION Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and deserved particular attention in Chinese adults.
Aged ; Arthritis, Rheumatoid ; Asians ; China/epidemiology* ; Humans ; Hypertension ; Middle Aged ; Multimorbidity

Objective:To describe the prevalence of multimorbidity and its secular trend, and to explore the common patterns of multimorbidity in Chinese adults.Methods:A total of 25 033 participants who attended the second resurvey of China Kadoorie Biobank (CKB) were included in the study. We used data collected both at baseline (2004-2008) and at resurvey (2013-2014). A total of 13 chronic conditions were included, defined by self-reported, physical examination, and blood sample testing. Multimorbidity was defined as co-existence of two or more chronic conditions. Patterns of multimorbidity were explored using hierarchical cluster analysis.Results:The mean age of participants was (51.5±10.1) years at baseline and (59.5±10.2) years at second resurvey. The prevalence of multimorbidity increased from 33.5% to 58.1% over (8.0±0.8) years of follow-up. The average number of chronic conditions per person increased from 1.15 to 1.82 and all participants increased 0.42 conditions per 5 years on average. Participants who were older, less educated or lived in urban areas had a higher prevalence of multimorbidity and a higher increase in the number of chronic conditions. The increase in the number of chronic conditions was also higher among smokers and heavy alcohol drinkers. The most common multimorbidity pattern in the present population consisted of obesity, hypertension, diabetes, stroke, and heart disease.Conclusions:The prevalence of multimorbidity in Chinese adults is increasing rapidly due to ageing population. Populations of different sociodemographic background and lifestyle habits may have different prevalence of multimorbidity and changes in rates over time.

Objective:To compare the consistency of frailty status measured by Fried phenotype and frailty index composed of different numbers of deficits, and their prospective associations with risk of mortality.Methods:Data of 23 615 participants from the second resurvey of the China Kadoore Biobank (CKB) was used. Fried phenotype was constructed using five phenotypes, and frailty indexes (FI) were constructed using 28 and 40 deficits, respectively. We calculated the Weighted Kappa coefficient to compare the consistency of three measures in the classification of frailty status. Cox regression was performed to analyze the association of frailty status with risk of mortality.Results:The frailty prevalence calculated by Fried phenotype, FI-28, and FI-40 were 5.4%, 7.9%, and 4.0%, respectively. The Kappa coefficients of Fried phenotype with FI-28 and FI-40 were 0.357 and 0.408, respectively. The Kappa coefficients of FI-28 and FI-40 was 0.712. During an average of (3.9±0.5) years of follow-up, 755 participants died. When Fried phenotype was used, compared with the robust participants, the prefrail and frail participants had increased risk of mortality, the multivariable-adjusted HRs were 1.60 (95% CI: 1.32-1.94) and 2.90 (95% CI: 2.25-3.73), respectively. When FI-28 was used, the corresponding HRs were 1.71 (95% CI: 1.39-2.11) and 2.52 (95% CI:1.95-3.27) for prefrail and frail participants, and when FI-40 was used, the corresponding HRs were 1.98 (95% CI:1.60-2.44) and 3.71 (95% CI: 2.80-4.91). The association of frailty status with mortality differed in different age groups, with the association stronger in younger adults than in older adults. Conclusion:Fried phenotype and frailty index constituted with different numbers of deficits showed good consistency; which can be used to well predict the risk of mortality.

Objective:To investigate whether ventricular non-excitatory electrical stimulation(NES)preconditioning can protect myocardial ischemia-reperfusion(IR)injury in aged mice by regulating cardiac calcitonin gene-related peptide(CGRP).Methods:Male C57BL/6J mice were randomly divided into 3 groups, (1)the Sham group, receiving sham operation group(n=6); (2)the IR group, receiving ligation of coronary artery to induce myocardial ischemia for 45 min and reperfusion for 120 min(n=13); (3)the NES group, IR model receiving NES from 15 min before IR to the end of reperfusion(n=13). Infarct size was detected by staining with 2, 3, 5-triphenyltetrazolium chloride.The level of serum cTnI and expression of myocardial CGRP were measured by enzyme linked immunosorbent assay and quantitative real time polymerase chain reaction.Results:Compared with the IR group, the infarct sizes were significantly lower in NES group[(38.17±4.36)% vs.(45.33±5.68)%, P<0.05]. Besides, the IR and NES groups were associated with significantly increased levels of serum cTnI[(10.89±2.14)μg/L, (7.03±1.79)μg/L vs.(3.92±0.47)μg/L, P<0.001], myocardial CGRP protein[(26.33±4.55)μg/kg, (19.67±5.79)μg/kg vs.(17.00±2.90)μg/kg, P<0.01], CGRP mRNA[(1.40±0.20), (2.20±0.75) vs.(1.05±0.10), P<0.01]compared with the Sham group.Furthermore, the NES group was associated with markedly decreased levels of serum cTnI and myocardial CGRP protein, and increased level of CGRP mRNA compared with the IR group(all P<0.05). Conclusion:NES may protect myocardium IR injury by regulating endogenous CGRP expression in aged mice.

Objective:To evaluate the effect of sevoflurane postconditioning on early inflammatory responses during intestinal ischemia-reperfusion (I/R) in rats.Methods:Sixty clean-grade Sprague-Dawley rats, aged 8-10 weeks, weighing 200-230 g, were divided into 3 groups ( n=20 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), and sevoflurane postconditioning group (Sevo group). Intestinal I/R was produced by occlusion of the superior mesenteric artery for 60 min followed by reperfusion for 2 h in anesthetized rats in I/R group and Sevo group.Laparotomy was performed, and the superior mesenteric artery was only isolated in Sham group.The rats inhaled 1.15% sevoflurane for 30 min for postconditioning in Sevo group.Blood samples were collected by cardiac puncture at 2 h of reperfusion, and then the rats were sacrificed.Samples of intestine were obtained for examination of the pathological changes of intestinal tissues (with a light microscope) which were scored according to Chiu and for determination of the neutrophil L-selectin levels in blood (by flow cytometry), tumor necrosis factor-alpha (TNF-a) expression (by Western blot), myeloperoxidase (MPO) activity (by spectrophotometry). Results:Compared with group Sham, the neutropil L-selectin level in blood was significantly increased in group I/R and decreased in group Sevo, and Chiu′s score, TNF-a expression and MPO activity were significantly increased in I/R and Sevo groups ( P<0.05). Compared with group I/R, the neutropil L-selectin level in blood, Chiu′s score, TNF-a expression, TNF-a expression and MPO activity were significantly decreased ( P<0.05), and the pathological changes were significantly attenuated in group Sevo. Conclusion:The mechanism by which sevoflurane postconditioning reduces intestinal I/R injury may be related to inhibiting early inflammatory responses in rats.