ObjectiveTo investigate the regulatory effect of icariin （ICA） on transforming growth factor-β₁ （TGF-β₁）/Smad pathway in bone microvascular endothelial cells （BMECs） and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured， and the cell types were identified by immunofluorescence. Cells were divided into the control group， model group （0.1 g·L^-1 methyl prednisolone）， ICA group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA）， and TGF-β inhibitor group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA +1×10^-5 mol·L^-1 LY2157299）. Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β₁/ Smad pathway. ResultsAfter cell separation culture， platelet endothelial cell adhesion molecule （CD31） and von willebrand factor （vWF） immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged， and the nucleus was pyknotic and broken in the model group. Compared with the model group， the ICA group had complete cell membranes， clear structures， with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes， and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group， in the model group and the LY2157299 group， autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group， the mRNA and protein expressions of autophagy effector protein 1 （Beclin1） and microtubule-associated protein 1 light chain 3B （LC3B） in the model group were significantly decreased （P<0.01）， and those of ubiquitin-binding protein （p62） were significantly increased （P<0.01）. The mRNA expression of TGF-β₁， Smad homolog 2 （Smad2）， and Smad homolog 3 （Smad3） decreased （P<0.05， P<0.01）. The protein expressions of TGF-β₁， p-Smad2， and p-Smad3 were significantly decreased （P<0.01）. Compared with those of the model group， the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased （P<0.01）， and those of p62 significantly reduced （P<0.01）. The mRNA expression of TGF-β₁， Smad2， and Smad3 increased significantly （P<0.01）. The protein expression of TGF-β₁， p-Smad2， and p-Smad3 increased significantly （P<0.01）. Compared with those in the model group， the mRNA and protein expressions of Beclin1， LC3B， and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β₁ pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs， and its mechanism may be related to activating the TGF-β₁/Smad signaling pathway.

This study investigated the therapeutic effects and mechanisms of medical ozone on sepsis- associated kidney injury (S-AKI) induced by lipopolysaccharide in mice. Using enzyme-linked immunosorbent assay, renal histopathological evaluation, detection of renal function biochemical indicators, immunofluorescence staining, and Western blot analysis, the effects of intraperitoneal injection of ozone on inflammation, coagulation, and renal tissue in mice were systematically detected.The results demonstrated that ozone treatment significantly reduced circulating levels of the specific markers (citrullinated histone H3 and myeloperoxidase-DNA complexes) from neutrophil extracellular traps (NETs) in S-AKI mice, with a suppression on inflammatory and tissue factor expression in renal tissue. Furthermore, ozone effectively improved microcirculation dysfunction, reduced tubular damage and interstitial inflammatory infiltration, thereby alleviating pathological changes of kidneys of S-AKI mice. Mechanistic studies revealed that ozone enhances phagocytic clearance of tissue factor-rich microparticles (TF-MPs) by activating the 5'-monophosphate-activated protein kinase (AMPK) / scavenger receptor (SR)-A1 signaling pathway in macrophages. In Sr-a1-/- mice, renoprotective effect of ozone was completely abolished, confirming the critical role of SR-A1 in this mechanism. In summary, this study demonstrates that medical ozone promotes macrophage clearance of TF-NETs complexes through the AMPK/SR-A1 signaling axis, exerting dual protective effects on mice through anti-inflammatory action and microcirculation improvement, which provides novel intervention targets and therapeutic strategies for S-AKI treatment.

The scientific interpretation of the theory of medicinal properties of TCM is a research hotspot in the modernization of TCM. It is of great value to clarify the property and degree of cold and heat in Chinese materia medica for guiding clinical precise medication. In recent years, the research on the cold and heat properties of Chinese materia medica has been carried out at the animal, cell and molecular levels. Based on the objective material basis of medicinal properties, from the perspective of biological effects such as thermodynamics and multiomics; with the help of infrared thermal imaging and other technologies for analysis; forming a variety of research models such as "property-structure relationship". Related research has developed from a single material component or index to a new model that tends to integrate multi-source information and multi-dimensional data. However, how to deal with the problems of large sample size, strong redundancy, high heterogeneity, and how to integrate multi-dimensional information are still research difficulties. With its powerful computing and learning ability, machine learning can show good discrimination and prediction ability in the study of cold and hot properties of Chinese materia medica, and play an important role in the study of cold and hot properties of Chinese materia medica. At present, the most widely used algorithms are linear discriminant analysis, Logistic discriminant analysis, support vector machine, decision tree, random forest and so on. The data dimension of the existing research needs to be enriched, the algorithm has room for further optimization, and a more detailed discriminant model of cold and hot properties of Chinese materia medica needs to be established.

Fungal keratitis is a serious blinding eye disease. The development of fungal infections depends primarily on the interaction of fungal virulence with host immune defense factors. The cornea is considered an immune-privileged organ, and resident macrophages are the main immune cells that respond to the heterogeneity exhibited by the microenvironment with their polarization. In the early stage of infection, macrophages polarize towards M1, which promotes inflammation and facilitates fungal clearance but produces a cellular storm that exacerbates immune damage; in the late stage of infection, macrophages polarize towards M2, which suppresses the inflammatory response and facilitates tissue repair, but may be immunosuppressed or even immune escape to the detriment of pathogen clearance. The balance between pro-inflammatory and anti-inflammatory responses is key to maintaining the functional integrity of the cornea. Current antifungal drug therapy is limited, so it is particularly important to find a therapeutic target for the inflammatory response triggered by the immune response in addition to antifungal therapy. In this review, the functional and phenotypic characterization of macrophage subsets associated with fungal keratitis was reviewed, more in-depth research is needed to explore the specific mechanisms by which macrophage polarization and their impact on fungal keratitis. Targeted regulation of macrophage differentiation based on their phenotype and function could be an effective approach to treat and manage fungal keratitis in the future.

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Objective To explore the value of plaque-to-aorta CT value ratio(standardized CT value)in differentiating coronary lipid and fibrous plaques,and to preliminarily analyze the stability of the cutoff.Methods Patients who underwent coronary computed tomography angiography(CCTA)and intravascular ultrasound(IVUS)within 1 week were included.The plaque CT value was obtained by measuring the all,four and two short-axis planes,respectively.The CT value of the ascending aorta was measured and standardized(plaque-to-aorta CT value ratio).The receiver operating characteristic(ROC)curves of the standardized and the traditional CT values were drawn.Results A total of 60 patients with 74 plaques were included,35 lipid and 39 fibrous plaques were diagnosed by IVUS.The aorta CT value was significantly correlated with the plaque(r=0.420,P<0.01);the cutoffs for the CT value of all,four and two plaque slices were 55 HU,48 HU and 52 HU,respectively,and all there of the cutoffs of standardized CT value were 0.149;the sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of four-slice traditional and standardized CT values to differentiate lipid and fibrous plaques were 69%,87%,83%,76%and 91%,82%,82%,91%,respectively.Conclusion Compared with traditional CT value,the standardized CT value can greatly improve the sensitivity and NPV in differentiating coronary lipid and fibrous plaques,while maintaining modest to high specificity and PPV.Furthermore,the cutoff is stable.

Background and purpose:Esophageal carcinoma(ESCA)is one of the malignant tumors with high mortality rate,and the underlying mechanism of its development is largely unknown.CDC20 plays an important role in tumorigenesis,and its dysregulated expression is closely related to tumor occurrence and development.The expression of CDC20 is increased in a variety of tumors,and knocking down CDC20 can inhibit tumor cell proliferation.NLRP3 is the main component of the inflammasome,and inflammasome is also closely related to tumor occurrence and development.Here,our study aimed to investigate whether CDC20 promotes the proliferation of ESCA cells through NLRP3 and its regulatory mechanism.Methods:The expression levels of CDC20 and NLRP3 genes in ESCA patients were analyzed using The Cancer Genome Atlas(TCGA)detabase and GTEx public database.We collected clinical and pathological data and tissues from 80 ESCA patients at the First Affiliated Hospital of Xinxiang Medical College,and detected the protein expression of NLRP3 in ESCA patients through immunohistochemistry staining.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).We studied the effects of knocking down CDC20 and NLRP3 gene on the proliferation ability of esophageal squamous cell carcinoma cells EC9706 and KYSE150 using short hairpin RNA(shRNA)technology.Co-immunoprecipitation(Co-IP),proteasome inhibitors and ubiquitination experiments were used to detect whether CDC20 interacts with NLRP3,and to elucidate whether CDC20 regulates NLRP3 expression through the ubiquitination pathway.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).Results:The TCGA database analysis showed that the expression levels of CDC20 and NLRP3 mRNA were significantly higher in the cancer tissues of ESCA patients than in the adjacent tissues.The immunohistochemistry results further showed that compared with adjacent tissues,the protein expression levels of CDC20 and NLRP3 were increased in ESCA tissues.Knocking down CDC20 and NLRP3 genes inhibited the proliferation of ESCA cells.Co-IP,proteasome inhibitors and ubiquitination experiments confirmed that CDC20 interacted with NLRP3 through its leucine-rich repeat(LRR),and CDC20 stabilized its expression by promoting NLRP3 ubiquitination.Conclusion:CDC20 and NLRP3 are upregulated in ESCA tissues,and CDC20 stabilizes their expression through ubiquitination of NLRP3,promoting ESCA cell proliferation.This suggests that CDC20 and NLRP3 may be potential diagnostic targets for ESCA.

The cardiovascular diseases, which have the increasing incidence and high mortality rate, have brought a great impact on people′s lives and health.Being lipid inclusions with 30~150 nm in diameter, exosomes can be secreted by most cells in the body, and proteins, lipids, nucleic acids and other substances derived from those cells are wrapped inside.Exosomes play a variety of biological roles in the communication between cells, such as mediating immune response, inflammatory response, cell migration and differentiation.Research on exosomes has made significant progress, and the roles of exosomes in cardiovascular diseases have consequently attracted more and more attention in recent years.The communication of exosomes between cardiomyocytes and between heart and peripheral tissues has provided new strategies for the diagnosis and treatment of cardiovascular diseases.Application of exosomes in the diagnosis and treatment of cardiovascular diseases such as heart failure, viral myocarditis, Kawasaki disease and dilated cardiomyopathy is summarized in this review.

OBJECTIVE：To establish UPLC fin gerprint of 32 compatible herb pairs with Polygonum multiflorum as the core ， and to conduct multivariate statistical analysis. METHODS ：UPLC method was adopted. Using P. multiflorum and single decoction pieces of compatible herb as reference ，UPLC fingerprints of 32 compatible herb pairs of P. multiflorum were drawn. Common peaks were confirmed by relative retention time and UV absorption spectrum. Non-supervised PCA and supervised OPLS-DA were conducted by using SPSS 19.0 software and SIMCA 13.0 software. RESULTS ：There were totally 12 common peaks in UPLC fingerprints of 32 compatible herb pairs of P. multiflorum . The results of non-supervised PCA showed that the accumulative variance contribution rate of primary 6 principal components was 84.633％. The results of cluster analysis of PCA comprehensive score showed that single decoction piece of P. multiflorum ，compatible herb pairs of P. multiflorum with Lycium barbarum ，Rehmannia glutinosa，Paeonia lactiflora ，Codonopsis pilosula ，Eclipta prostrate ，Angelica sinensis ，Glycyrrhiza uralensis ，Astragalus membranaceus and Ophiopogon japonicus were clustered into one category ；others were clustered into one category. Results of supervised OPLS-DA analysis showed that eigen values of 4 principal components were 2.32，2.61，1.58 and 0.90，respectively. There were differences in the contents of 12 common components in the compatibility of P. multiflorum with tonic medicine and non-tonic medicine. The changes of the content of the components after compatibility with tonic medicine were similar. Common peak 7，4，6，3 were main reasons for the differences （variable importance projection value were all higher than 1）. CONCLUSIONS：Established fingerprint is simple in operation ，and can be combined with multivariate statistical analysis to evaluate the content changes of common components of 32 compatible herb pairs with P. multiflorum as the core.

Objective: To investigate the clinical efficacy of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein combined with sodium hyaluronate in the treatment of rheumatoid arthritis (RA). Methods: Forty adult RA patients (12 males, 28 females) aged from 36 to 79 were selected in Department of Rheumatology of the Second People′s hospital of Datong from February 2016 to February 2018.The patients were randomly divided into the observation group and the control group according to the digital table, with 20 cases in each group.The observation group was treated by intra-articular injection of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein and sodium hyaluronate, and the control group was only treated with recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein.The joint swelling, joint pain, joint mobility, morning stiffness, X-ray grade and total effective rate of the two groups were statistically analyzed before and after treatment. Results: Before treatment, there were no statistically significant differences in joint swelling, joint pain, joint mobility, morning stiffness, clinical score and X-ray grade between the two groups (all P>0.05). After treatment, the symptoms and signs of the two groups were obviously improved.The joint pain, joint pressure pain, joint activity, morning stiffness and clinical score in the observation group were (1.2±1.2)points, (0.8±0.7)points, (0.5±0.4)points, (0.7±0.7)points and (4.5±2.6)points, respetively, which were significantly better than those in the control group [(2.2±1.4)points, (1.5±0.9)points, (1.5±0.9)points, (1.5±0.6)points and (8.6±4.6)points, U=125, 111, 68, 89 and 97, all P<0.05]. The total effective rate of the observation group was 100% (20/20), while that of the control group was 75% (15/20), there was statistically significant difference between the two groups (χ²=14.10, P<0.01). Conclusion The injection of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein combined with sodium hyaluronate in the treatment of RA can effectively improve the clinical symptoms of RA patients, and it is more effective than single use.It is worthy of popularizing in clinic.