ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

OBJECTIVE: To develop and compare risk prediction models for in-hospital post-cardiac arrest brain injury (PCABI) in critically ill patients using nomograms and random forest algorithms, aiming to identify the optimal model for early identification of high-risk PCABI patients and providing evidence for precise treatment. METHODS: A retrospective cohort study was used to collect the first-time in-hospital cardiac arrest (IHCA) patients admitted to the intensive care unit (ICU) from 2008 to 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) as the study population, and the patients' age, gender, body mass, health insurance utilization, first vital signs and laboratory tests within 24 hours of ICU admission, mechanical ventilation, and critical care scores were extracted. Independent influencing factors of PCABI were identified through univariate and multivariate Logistic regression analyses. The included patients were randomly divided into a training cohort and an internal validation cohort in a 7:3 ratio, and the PCABI risk prediction model was constructed by the nomogram and random forest algorithm, respectively, and the model was evaluated by receiver operator characteristic curve (ROC curve), the calibration curve, and the decision curve analysis (DCA), and after the better model was selected, 179 patients admitted to Tianjin Medical University General Hospital as the external validation cohort for external evaluation were collected by using the same inclusion and exclusion criteria. RESULTS: A total of 1 419 patients with without traumatic brain injury who had their first-time IHCA were enrolled, including 995 in the training cohort (including 176 PCABI and 819 non-PCABI) and 424 in the internal validation cohort (including 74 PCABI and 350 non-PCABI). Univariate and multivariate analysis showed that age, potassium, urea nitrogen, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation III (APACHE III), and mechanical ventilation were independent influences on the occurrence of PCABI in patients with IHCA (all P < 0.05). Combining the above variables, we constructed a nomogram model and a random forest model for comparison, and the results show that the nomogram model has better predictive efficacy than the random forest model [nomogram model: area under the ROC curve (AUC) of the training cohort = 0.776, with a 95% credible interval (95%CI) of 0.741-0.811; internal validation cohort AUC = 0.776, with a 95%CI of 0.718-0.833; random forest model: AUC = 0.720, with a 95%CI of 0.653-0.787], and they performed similarly in terms of calibration curves, but the nomogram performed better in terms of decision curve analysis (DCA); at the same time, the nomogram model was robust in terms of external validation cohort (external validation cohort AUC = 0.784, 95%CI was 0.692-0.876). CONCLUSIONS A nomogram risk prediction model for the occurrence of PCABI in critically ill patients was successfully constructed, which performs better than the random forest model, helps clinicians to identify the risk of PCABI in critically ill patients at an early stage and provides a theoretical basis for early intervention.
Humans ; Critical Illness ; Retrospective Studies ; Heart Arrest/complications* ; Nomograms ; Brain Injuries/etiology* ; Intensive Care Units ; Algorithms ; Male ; Female ; Middle Aged ; ROC Curve ; Risk Factors ; Risk Assessment ; Logistic Models ; Aged

This study aims to understand the biological characteristics of Streptococcus dysgalacti-ae of yak origin.Bacterial isolation and identification,drug susceptibility test,virulence gene test and pathogenicity test were carried out on milk samples of yaks from Naqu City to evaluate the bi-ological characteristics of the isolated strains.Meanwhile,molecular biological information such as virulence factors and drug resistance genes were analyzed by whole genome sequencing,and viru-lence genes were verified by PCR.The results showed that a strain of Streptococcus dysgalactiae was isolated from the milk of yak,and its colony morphology was pinpoint size,smooth edge and milky white.This strain is sensitive to many antibiotics(penicillin G,cephalosporin,ciprofloxacin,tetracycline,erythromycin,etc.).Virulence gene test results showed that the strain carries six key virulence genes(cyl,eno,scpB,bca,bac and napr),which may be closely related to its pathoge-nicity.In the pathogenicity test,the mice were listless and less active after infection,but no death occurred during the observation period.The pathological changes of spleen,kidney,liver and lung tissue were found,suggesting that the strain had certain pathogenic potential but not high lethali-ty.Whole genome sequencing data showed that the gene length of this strain was 4 079 280 bp,the GC content was 39.41％,3 964 coding genes were predicted,604 of which were annotated as viru-lence factors,and another 28 gene mutations may enhance its pathogenic ability.Through annota-tion of CARD database,two Pat A resistance genes and two lmrp resistance genes were found,re-vealing their potential resistance mechanism.Through whole genome sequencing technology and bioinformatics analysis method,this study revealed the genomic characteristics,drug resistance and pathogenicity mechanism of Streptococcus dysgalactiae of yak origin.The findings provide impor-tant scientific evidence for further exploration of the pathogenicity,drug resistance mechanisms,and molecular evolution of yak-derived Streptococcus agalactiae.

This study aims to understand the biological characteristics of Streptococcus dysgalacti-ae of yak origin.Bacterial isolation and identification,drug susceptibility test,virulence gene test and pathogenicity test were carried out on milk samples of yaks from Naqu City to evaluate the bi-ological characteristics of the isolated strains.Meanwhile,molecular biological information such as virulence factors and drug resistance genes were analyzed by whole genome sequencing,and viru-lence genes were verified by PCR.The results showed that a strain of Streptococcus dysgalactiae was isolated from the milk of yak,and its colony morphology was pinpoint size,smooth edge and milky white.This strain is sensitive to many antibiotics(penicillin G,cephalosporin,ciprofloxacin,tetracycline,erythromycin,etc.).Virulence gene test results showed that the strain carries six key virulence genes(cyl,eno,scpB,bca,bac and napr),which may be closely related to its pathoge-nicity.In the pathogenicity test,the mice were listless and less active after infection,but no death occurred during the observation period.The pathological changes of spleen,kidney,liver and lung tissue were found,suggesting that the strain had certain pathogenic potential but not high lethali-ty.Whole genome sequencing data showed that the gene length of this strain was 4 079 280 bp,the GC content was 39.41％,3 964 coding genes were predicted,604 of which were annotated as viru-lence factors,and another 28 gene mutations may enhance its pathogenic ability.Through annota-tion of CARD database,two Pat A resistance genes and two lmrp resistance genes were found,re-vealing their potential resistance mechanism.Through whole genome sequencing technology and bioinformatics analysis method,this study revealed the genomic characteristics,drug resistance and pathogenicity mechanism of Streptococcus dysgalactiae of yak origin.The findings provide impor-tant scientific evidence for further exploration of the pathogenicity,drug resistance mechanisms,and molecular evolution of yak-derived Streptococcus agalactiae.

Objective To determine the optimal conditions for CXCR4 upregulation by comparing the expression levels of chemokine(C-X-C motif)receptor 4(CXCR4)in MSCs cultured with varying concentrations of oxygen and hydrogen peroxide(H2O2).Methods MSCs were cultured with 0.1％,1％,or 3％O2 and 50 μmol/L H2O2 for different lengths of time(3,6,12,and 24 h).The mRNA and protein expressions of CXCR4 in MSCs were measured by real-time quantitative PCR(qPCR),Western blotting,and immunofluorescence staining.The viability and chemotactic ability of MSCs were measured using CCK-8,wound-healing and Transwell migration assays.Results Both hypoxia and H2O2 treatment were found to upregulate MSC expressions of CXCR4 to some extent.The mRNA and protein levels of CXCR4 were higher after 6-12 h of culture of MSCs with 3％O2,and significantly higher when treated with H2O2 for 6 h.Cell viability was significantly increased after culture with 3％O2 compared with the control group and both 3％O2 and H2O2 pretreatment could enhance chemotactic migration in MSCs.Conclusion Culture with 3％O2 and H2O2 pretreatment can upregulate CXCR4 expressions in MSCs and enhance migration in cells,with superior effects observed with 3％O2.Therefore,treatment with 3％O2 represents the best choice for upregulating the chemotactic ability of MSCs.

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

Background Previous studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet. Objective To evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers. Methods A total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q₁-Q₄) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models. Results The workers' medians (P₂₅, P₇₅) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L^-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q₁ group, blood aluminum in the Q₂, Q₃, or Q₄ group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, P_trend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, P_trend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, P_trend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (P_trend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (P_trend>0.05). Conclusion Occupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.

Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.