ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Chronic heart failure(CHF) is a comprehensive clinical syndrome caused by multiple factors that result in structural and/or functional abnormalities of the heart, leading to impaired ventricular contraction and/or relaxation functions. This medical condition represents the final stage of various cardiovascular diseases. In the treatment of CHF, multiple clinical studies have demonstrated the benefits of using traditional Chinese medicine(TCM) to control oxidative stress, inflammation, and apoptosis, thereby delaying ventricular remodeling and reducing myocardial fibrosis. In this study, common TCM syndromes in the diagnosis and treatment of CHF in recent years were reviewed and summarized. Five common treatment methods including benefiting Qi and activating blood circulation, enhancing Qi and nourishing Yin, warming Yang for diuresis, eliminating phlegm and dampness, rescuing from collapse by restoring Yang, and corresponding classic prescriptions in prevention and treatment of CHF were concluded under the guidance of TCM syndrome differentiation thinking. Meanwhile, research progress on the modern pharmacological effects of these classic prescriptions was systematically discussed, so as to establish a unique treatment system for CHF by classic prescriptions under the guidance of TCM syndrome differentiation theory and provide innovative diagnosis and treatment strategies for clinical CHF.
Humans ; Medicine, Chinese Traditional ; Heart Failure/drug therapy* ; Chronic Disease ; Syndrome

OBJECTIVE: To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA. METHODS: Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1β (IL-1β)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs. RESULTS: The 10 μM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1β, and reduced the effect of IL-1β on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs. CONCLUSION Salvianolic acid A attenuated the IL-1β-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.
Humans ; Apoptosis ; Cartilage/metabolism* ; Chondrocytes/metabolism* ; Interleukin-1beta/metabolism* ; Matrix Metalloproteinase 3/metabolism* ; MicroRNAs/metabolism*

Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; Etoposide ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma/therapy* ; Melphalan ; Transplantation Conditioning ; Transplantation, Autologous

Objective:To explore the reoperation rate and risk factors of adjacent segment disease (ASDis) in patients with lumbar degenerative diseases after transforaminal lumbar interbody fusion (TLIF).Methods:The clinical data of 460 patients who underwent TLIF for lumbar degenerative diseases in our hospital from January 2011 to December 2013 were retrospectively analyzed. There were 204 males and 256 females with an age of 54.6±12.6 years (range, 20-85 years). Divided into ASDis group and None ASDis (N-ASDis) group according to the occurrence of ASDis and received surgical treatment. The age of ASDis group was 57.9±12.2 years, with 14 males and 12 females, while the age of N-ASDis group was 54.4±12.5 years, with 188 males and 246 females. Count the reoperation rate of ASDis. Compare the age, body mass index (BMI), comorbidities, surgery-related parameters, length of stay, imaging parameters before and after surgery between the two groups, and use univariate analysis and logistic regression analysis to explore risk factors for ASDis.Results:Among 460 patients who underwent TLIF due to lumbar degenerative diseases, 26 patients developed ASDis and received surgical treatment, the reoperation rate was about 5.7%. Among them, the reoperation rate of ASDis with above Pfirrmann grade III in the adjacent intervertebral disc was about 53.1% (17/32). The average onset time of adjacent segment disease was 76.3±25.0 months (range, 30-111 months). Univariate analysis showed that BMI ( t=3.86, P<0.001), history of hypertension (χ 2=5.30, P=0.021), preoperative adjacent vertebral disc degeneration (χ 2=85.90, P<0.001), preoperative adjacent spinal canal stenosis (χ 2=25.35, P<0.001), and preoperative intervertebral space height of adjacent segments ( t=4.33, P<0.001) were statistically different among patients with or without ASDis. Incorporating the above indicators into the logistic regression model, the analysis results showed that body mass index (BMI) >24.9 kg/m 2 and preoperative adjacent intervertebral disc degeneration ≥III degree were risk factors for ASDis after TLIF. Conclusion:The reoperation rate of ASDis after TLIF in patients with lumbar degenerative disease is about 5.7%. BMI>24.9 kg/m 2 and preoperative adjacent intervertebral disc degeneration ≥III degree are risk factors for ASDis and received surgical treatment after TLIF.

OBJECTIVE: To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia. METHODS: Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively. RESULTS: In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G^-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G⁺) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G⁺ bacteria (39.2%) and 45 strains of G^- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G^- bacteria accounted for 47.4% and G⁺ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G⁺ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum β-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G^- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G⁺ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G^- bacteria infection was (11.02±20.282) ng/ml, while in G⁺ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G^- infection was (76.33±69.946) mg/L, and that in G⁺ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae. CONCLUSION G^- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G^- bacteria dominates in ALL, while G⁺ bacteria and G^- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G⁺ bacteria. The mean value of PCT and CRP are significantly higher in G^- bacteria infection than in G⁺ bacteria.
Acute Disease ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/microbiology* ; Bacteria ; Child ; Drug Resistance, Bacterial ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Microbial Sensitivity Tests ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Procalcitonin ; Retrospective Studies ; Sepsis/drug therapy*