Objective To investigate the effects of pretreatment with Xuebijing injection on renal tubular injury in rats with contrast-induced acute kidney injury(CI-AKI).Methods Twenty-four Sprague-Dawley(SD)rats were selected and divided into normal group,model group,control group,and treatment group according to the random number table method,with 6 rats in each group.The animal model of CI-AKI was prepared by adopting iohexol,and the normal group was not subjected to any treatment.The rats in the treatment group were injected with Xuebijing injection via the tail vein 15 hours before modeling until 24 hours after modeling.The injection volume was 10 mL/kg for every 6 hours.The control group was injected with normal saline at the same time point.After 24 hours of modeling,the urine of rats in each group was collected to determine the levels of blood urea nitrogen(BUN)and urine N-acetyl-β-D-gluco-aminidase(uNAG),and the blood was collected to determine the levels of serum creatinine(SCr).Then the rats were killed and the kidney tissues were extracted,and then stained with hematoxylin-eosin(HE),and the pathological changes of the kidney tissues were observed under the light microscope.Results BUN,SCr and uNAG were significantly higher in the model group than those in the normal group[BUN(μmol/L):37.29±6.18 vs.6.37±1.19,SCr(mmol/L):30.43±4.44 vs.14.90±1.61,uNAG(U/L):47.77±4.71 vs.11.32±3.62,all P<0.01];BUN,SCr and uNAG levels were obviously decreased in the treatment group compared to the model group[BUN(μmol/L):9.45±3.04 vs.37.29±6.18,SCr(mmol/L):19.83±2.16 vs.30.43±4.44,uNAG(U/L):21.70±6.21 vs.47.77±4.71,all P<0.05],however,BUN and uNAG in the treatment group were still significantly higher than those in the normal group[BUN(μmol/L):9.45±3.04 vs.6.37±1.19,uNAG(U/L):21.70±6.21 vs.11.32±3.62,P<0.05 or P<0.01];SCr in the treatment group was not statistically significant compared to the normal group(μmol/L:19.83±2.16 vs.14.90±1.61,P>0.05).Under the light microscope,the renal tubular epithelial cells at the junction of cortex and dermatomedulla in the kidneys of the model group were obviously vacuolated,accompanied by cell detachment and necrosis,and the tubules were dilated,with no obvious lesions in the glomeruli.The degree of damage in the control group and the treatment group was reduced compared with that in the model group.The degree of renal tubular damage in the model group was higher than that in the normal group;while the degree of renal tubular damage in the control group was significantly lower than that in the model group;and the degree of renal tubular damage in the treatment group was lower than that in the model group.There was no statistically significant difference in the degree of renal tubular damage between the treatment group and the control group.Conclusion Xuebijing injection may exert a protective effect on renal function in rats with CI-AKI by attenuating renal tubular injury.

Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.

Objective To compare the effects of 2 vascular accesses via arteriovenous fistula(AVF)and tunnel-cuffed catheter(TCC)in elderly patients with maintenance hemodialysis(MHD).Methods A total of 103 elderly MHD patients were selected and divided into the AVF group(43 cases)and the TCC group(60 cases)according to different vascular pathways.Laboratory indexes of serum creatinine,uric acid,parathyroid hormone(PTH),serum calcium,blood phosphorus,hemoglobin,triglyceride and total cholesterol were compared between the two groups on dialysis day after receiving regular hemodialysis treatment for 1 year.Blood flow and urea clearance in vascular pathway were also compared between the two groups.The left ventricular end-diastolic diameter(LVEDd),the left ventricular posterior end-diastolic thickness(LVPWT),the ventricular septal end-diastolic thickness(IVSTd),ejection fraction(EF),the maximum flow velocity ratio(E/A)of the left atrial ventricle at the early and late diastolic stages and pulmonary artery pressure were examined by echocardiography after regular hemodialysis treatment for 1 year.The occurrence rates of left ventricular systolic dysfunction and diastolic dysfunction were recorded.Hemodialysis access associated infection,mechanical injury and heart failure during dialysis were also recorded.Results There were no significant differences in laboratory indexes between the two groups(P＞0.05).LVEDd,IVSTd,LVPWT,incidence rates of left ventricular systolic dysfunction,diastolic dysfunction,blood flow through vascular channels,Kt/V and mechanical injury were higher in the AVF group than those in the TCC group,while the ratio of hemodialysis access associated infection,E/A and EF values were lower in the AVF group than those in the TCC group(P＜0.05).There were no significant differences in incidence rates of pulmonary arterial pressure and heart failure between the two groups(P＞0.05).Conclusion For elderly MHD patients,the appropriate dialysis access should be determined after evaluating underlying diseases and vascular conditions.

Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.

RNA methylation modification is a highly dynamic and reversible epigenetic regulatory mechanism, primarily controlled by 3 types of factors: Methyltransferases, demethylases, and methylation reader proteins. N⁶-methyladenosine (m⁶A) methylation is the most common form of RNA methylation, and dysregulation of this process may lead to the development of various diseases. Renal diseases have drawn considerable attention owing to their high incidence, poor prognosis, and substantial socioeconomic burden. Renal resident cell injury plays a crucial role in the onset and progression of various kidney diseases. Understanding the mechanisms underlying renal resident cell injury is essential for advancing the prevention and treatment of kidney diseases. Recent studies have revealed that RNA m⁶A methylation plays a critical role in renal resident cell injury, highlighting its potential as a novel therapeutic target for kidney disease treatment.
Humans ; Methylation ; Adenosine/metabolism* ; Methyltransferases/metabolism* ; Kidney/metabolism* ; Kidney Diseases/pathology* ; Epigenesis, Genetic ; RNA/genetics* ; RNA Methylation

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Objective:To comprehensively understand the operational status and existing problems of the neurosurgery professional training bases for standardized residency training in Guangdong Province.Methods:According to the scoring rules of "Standardized Residency Training Evaluation Indicators—Surgery (Neurosurgery) Professional Base" formulated by the Post-Graduation Medical Education Neurosurgery Professional Committee of the Chinese Medical Doctor Association, 28 training bases were supervised and evaluated. The scoring results of the supervision of 28 neurosurgery training bases were collected, and the training bases were divided into two categories according to the traditional teaching history, 6 affiliated hospitals of traditional medical schools and 22 non-traditional affiliated/teaching hospitals. GraphPad 5.0 software was used for statistical analysis of the 14 core indicators, and t-test, variance analysis and Chi-square test were used for analysis. Results:The results showed that there was a statistically significant difference in the compliance rate of 14 core indicators between traditional teaching hospitals and non-traditional teaching hospitals ( P = 0.003), skill operation and type and number of surgeries ( P = 0.041) and student rotation plan ( P = 0.012). The differences were also statistically significant. Conclusion:This study reveals that the comprehensive management ability of training bases in traditional teaching hospitals is significantly better than that in non-traditional teaching hospitals. Additionally, it's suggested to strengthen the construction of professional bases, enhance the institutionalized management of bases, and thus realize the homogenization training of neurosurgery residents.

The heart and kidney damage is a clinical disease commonly seen, the 2 organs can interact with each other as cause and effect, leading to a series of clinical symptoms which is the cardiorenal syndrome (CRS). In 2008, according to the connection between the heart and kidney, the nephrologists Ronco, etc, completed the definition and classification of CRS, including type Ⅰ and type Ⅲ of CRS being acute cardiorenal syndrome (ACRS). ACRS refers to the fact that when the damage of heart or kidney dysfunction influences each other leading to a clinical syndrome caused by a sharp deterioration of cardiorenal function. At present, no definite diagnostic criteria for ACRS have yet been made. The pathogenesis of ACRS may be related to the renin-angiotensin-aldosterone system (RAAS), nitric oxide-reactive oxygen species (NO-ROS) system, inflammatory reaction, the excessive activation of sympathetic nervous system and so on. Clinically, about 50% of ACRS patients are accompanied by acute decompensated cardiorenal dysfunction or failure, that seriously impact on the patients' clinical prognosis and survival rate, so it is necessary to find an effective therapeutic regimen. At present, the treatments of ACRS have mainly the diuretic, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor inhibitor (ARB), β-receptor blocker, positive inotropic drugs, recombinant human erythropoietin, recombinant human brain natriuretic peptide, continuous blood purification (CBP) etc, and traditional Chinese medicine (TCM) also has a certain effect for improving the clinical symptoms of ACRS patients. Now the pathogenesis, diagnosis, and combined treatment of TCM and western medicine for treatment of ACRS are summarized.

Objective: To explore the correlation between thromboelastography (TEG) parameters and the risk of venous thromboembolism (VTE) and bleeding in patients receiving anticoagulant therapy in surgical intensive care unit (SICU). Methods: 205 patients received low molecular weight heparin (LMWH) anticoagulant therapy admitted to SICU of Tianjin Hospital from December 2016 to December 2017 were consecutively enrolled. TEG detection was performed in all patients at 1 day after anticoagulation therapy, and coagulation reaction time (R value), blood clot generation time (K value), blood clot generation rate (α angle) and maximum width value (MA value) were recorded. At the same time, the traditional coagulation function test was carried out, and prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer levels were also recorded. The incidence of deep venous thrombosis (DVT), pulmonary embolism (PE) and bleeding during hospitalization were observed. Multivariate Logistic regression analysis was used to analyze the risk factors for VTE and bleeding in patients receiving anticoagulant therapy. Results: Of 205 patients, during the anticoagulant treatment, 14 patients developed DVT, and 4 patients with PE (2 of them were combined with DVT) with an incidence of 7.8% (16/205). There were 2 patients suffering from cerebral hemorrhage, 2 patients with gastric bleeding, and 1 patient with intra-tracheal hemorrhage with an incidence of 2.4% (5/205). Compared with the patients without VTE or bleeding, the R value of TEG in patients with VTE was significantly lowered (minutes: 4.6±2.2 vs. 7.4±1.4, P < 0.01), which was significantly increased in patients with hemorrhagic complications (minutes: 12.1±1.1 vs. 7.4±1.4, P < 0.01). There was no significant difference in the K value, α angle, MA value of TEG, or PT, APTT, D-dimer between the patients with and without VTE or bleeding. Multivariate Logistic regression analysis revealed that the R value of TEG was independent risk factor for incidence of VTE and hemorrhagic complication in SICU patients who receiving anticoagulation therapy [VTE: β = 0.386, odds ratio (OR) = 1.096, 95% confidence interval (95%CI) = 1.021-2.361, P = 0.006; hemorrhagic complication: β = -1.213, OR = 1.051, 95%CI = 1.017-3.458, P = 0.045]. Conclusion The R value of TEG is associated with the occurrence of VTE and hemorrhagic complications in patients receiving anticoagulant therapy in SICU.

OBJECTIVE: To explore the correlation between thromboelastography (TEG) parameters and the risk of venous thromboembolism (VTE) and bleeding in patients receiving anticoagulant therapy in surgical intensive care unit (SICU). METHODS: 205 patients received low molecular weight heparin (LMWH) anticoagulant therapy admitted to SICU of Tianjin Hospital from December 2016 to December 2017 were consecutively enrolled. TEG detection was performed in all patients at 1 day after anticoagulation therapy, and coagulation reaction time (R value), blood clot generation time (K value), blood clot generation rate (α angle) and maximum width value (MA value) were recorded. At the same time, the traditional coagulation function test was carried out, and prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer levels were also recorded. The incidence of deep venous thrombosis (DVT), pulmonary embolism (PE) and bleeding during hospitalization were observed. Multivariate Logistic regression analysis was used to analyze the risk factors for VTE and bleeding in patients receiving anticoagulant therapy. RESULTS: Of 205 patients, during the anticoagulant treatment, 14 patients developed DVT, and 4 patients with PE (2 of them were combined with DVT) with an incidence of 7.8% (16/205). There were 2 patients suffering from cerebral hemorrhage, 2 patients with gastric bleeding, and 1 patient with intra-tracheal hemorrhage with an incidence of 2.4% (5/205). Compared with the patients without VTE or bleeding, the R value of TEG in patients with VTE was significantly lowered (minutes: 4.6±2.2 vs. 7.4±1.4, P < 0.01), which was significantly increased in patients with hemorrhagic complications (minutes: 12.1±1.1 vs. 7.4±1.4, P < 0.01). There was no significant difference in the K value, α angle, MA value of TEG, or PT, APTT, D-dimer between the patients with and without VTE or bleeding. Multivariate Logistic regression analysis revealed that the R value of TEG was independent risk factor for incidence of VTE and hemorrhagic complication in SICU patients who receiving anticoagulation therapy [VTE: β = 0.386, odds ratio (OR) = 1.096, 95% confidence interval (95%CI) = 1.021-2.361, P = 0.006; hemorrhagic complication: β = -1.213, OR = 1.051, 95%CI = 1.017-3.458, P = 0.045]. CONCLUSIONS The R value of TEG is associated with the occurrence of VTE and hemorrhagic complications in patients receiving anticoagulant therapy in SICU.
Anticoagulants ; Critical Care ; Heparin, Low-Molecular-Weight ; Humans ; Pulmonary Embolism ; Risk Factors ; Thrombelastography ; Venous Thromboembolism