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Background To investigate lncRNA/circRNA-associated competing endogenous RNA (ceRNA)-gene regulation underlying leukocyte functions and characteristics, especially the potential ceRNA biomarkers, implicated in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). Methods Based on RNA-sequencing approach, comparing with healthy control population, we identified the PDHS- or PQDS-specific lncRNAs/circRNAs in leukocytes, especially the Zheng (syndrome)-specific ceRNAs and their corresponding ceRNA regulatory networks, further decoding their potential functions and pathways. Results Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific lncRNAs/circRNAs in leukocytes were not same in PQDS and PDHS. There were the Zheng-specific lncRNA/circRNA-associated ceRNAs identified in the leukocytes, and their corresponding ceRNA regulatory networks were generated, including the ceRNA-gene binary relationship networks and the miRNA-centered ceRNA-miRNA-gene triple relationship networks. In the generated Zheng-specific ceRNA networks, the PQDS-specific ceRNA-governed genes in leukocytes, keeping more complex interactions with each other, were enriched in pathways related to MAPK signaling, receptor tyrosine kinases signaling as well as complement and coagulation cascades. Notably, the enriched pathways associated with adherens junction, focal adhesion, ECM-receptor interaction, ECM-organization and cell surface interactions, were implicated in cell-to-cell adhesion/junction and communication, probably contributing to the characteristics and functions of leukocytes. The PDHS-specific ceRNA-regulated genes, seemed to have no more interactions with each other, were enriched in the biological processes related to regulation of cell morphogenesis, neutrophil activation and degranulation, and lymphocyte mediated immunity such as B-cell receptor signaling, complement and coagulation cascades, and regulation of NK/T-cell mediated cytotoxicity. Importantly, the five exosome-encapsuled ceRNAs, containing ZFAS1 (NR_036658.2), AL353719.1 (ENST00000566847), LOH12CR2 (NR_024061.1) and two new lncRNAs (TCONS_00038035 and TCONS_00027600), particularly higher expression in the leukocytes in PQDS rather than PDHS, could be the potential ceRNA biomarkers for differentiation of the TCM-defined PQDS and PDHS among CAG patients. Conclusions These results may provide new insights into the characteristic and functional changes of leukocytes in the two TCM Zhengs, especially the Zheng-specific ceRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte biomarkers for future application in integrative medicine.

A variety of podocyte antigens have been identified in human membranous nephropathy (MN), which is divided into various antigen-dominated subtypes, confirming the concept that MN is the common pattern of glomerular injury in multiple autoimmune responses. The detection of autoantibodies has been widely used, which promoted the clinical practice of MN toward personalized precision medicine. However, given the potential risks of immunosuppressive therapy, more autoantibodies and biomarkers need to be identified to predict the prognosis and therapeutic response of MN more accurately. In this review, we attempted to summarize the autoantigens/autoantibodies and autoimmune mechanisms that can predict disease states based on the current understanding of MN pathogenesis, especially the podocyte injury manifestations. In conclusion, both the autoimmune response and podocyte injury require multidimensional attention in the disease course of MN.

Rheumatoid arthritis (RA) is a chronic, systemic, synovitis-based inflammatory disease with unknown etiology. Neutrophils play important roles in the pathogenesis of RA. Apoptosis and NETosis of neutrophils are two major mechanisms of programmed cell death that differ in their morphological characteristics and effects on the immune system. In rheumatoid arthritis, delayed neutrophil apoptosis amplifies the inflammatory response; and massive release of NETs and their components may cause tissue damage and provide self-antigens. Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs. In this study, we evaluated the effect of emodin on a murine adjuvant-induced arthritis (AA) model of RA in vivo and on neutrophil apoptosis and NETosis in vitro. Our results show that emodin alleviated AA by reducing neutrophil infiltration and proinflammatory cytokine (interleukin-6, interferon-gamma and tumor necrosis factor-α) release. Emodin promoted apoptosis and inhibited autophagy and NETosis in neutrophils. These findings indicate that emodin represents a potential therapeutic agent for RA.

Objective: Propionibacterium acnes (P. acnes) plays an important role in the development of acne, an inflammatory skin disease with a high-incidence. In this study, we used high-throughput RNA sequencing (RNA-seq) to reveal the anti-inflammatory mechanism of baicalin on P. acnes-induced acne in rabbits. Methods: The Kligman method was used to induce acne in the ears of New Zealand rabbits. The effect of baicalin on the acne model was evaluated by the number of acne lesions and hematoxylin and eosin (H&E) staining of acne tissues. Enzyme-linked immunoabsorbent assay was used to measure the protein expression levels of tumor necrosis factor α (TNFA), interleukin-1 β (IL1B), IL6, and IL8 in the serum of rabbits. RNA-seq was performed to investigate the mechanism of anti-inflammatory activities of baicalin on acne. Immunohistochemical analysis and Western blot were used to validate the expression levels of related proteins in acne tissues. Results: Baicalin treatment significantly reduced the number of acne lesions and lesions of the ear as well as levels of serum inflammatory cytokines. RNA-seq data showed that baicalin treatment globally suppressed inflammation, especially the TNF signaling pathway and Staphylococcus aureus infection pathway, in the rabbit acne model. Conclusion: Baicalin effectively ameliorates P. acnes-induced acne in rabbits by suppressing the inflammatory response in rabbits. Keywords: Acne, Baicalin, P. acnes, TNF signaling pathway, Complement pathway

Background Liver diseases and related complications are major sources of morbidity and mortality, which places a huge financial burden on patients and lead to nonnegligible social problems. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently required. Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are frequently used herbal medicines in traditional Chinese medicine (TCM) formulas for the treatment of diverse ailments. A variety of bioactive ingredients have been isolated and identified from AFI and AF, including alkaloids, flavonoids, coumarins and volatile oils. Main body Emerging evidence suggests that flavonoids, especially hesperidin (HD), naringenin (NIN), nobiletin (NOB), naringin (NRG), tangeretin (TN), hesperetin (HT) and eriodictyol (ED) are major representative bioactive ingredients that alleviate diseases through multi-targeting mechanisms, including anti-oxidative stress, anti-cytotoxicity, anti-inflammation, anti-fibrosis and anti-tumor mechanisms. In the current review, we summarize the recent progress in the research of hepatoprotective effects of HD, NIN, NOB, NRG, TN, HT and ED and highlight the potential underlying molecular mechanisms. We also point out the limitations of the current studies and shed light on further in-depth pharmacological and pharmacokinetic studies of these bioactive flavonoids. Conclusion This review outlines the recent advances in the literature and highlights the potential of these flavonoids isolated from AFI and AF as therapeutic agents for the treatment of liver diseases. Further pharmacological studies will accelerate the development of natural products in AFI and AF and their derivatives as medicines with tantalizing prospects in the clinical application.

BACKGROUND Fibrinogen-like protein 2 (FGL2) is a member of the fibrinogen-like protein family and possesses important regulatory functions in both innate and adaptive immune responses. FGL2 is overexpressed in glioma, and its expression level is negatively associated with the prognosis of glioma patients. However, the diagnostic value of FGL2 is unknown in breast carcinoma. MATERIAL AND METHODS We comprehensively analyzed the expression pattern of FGL2 in breast cancer. Several online databases - TCGA, Oncomine, GEPIA, Kaplan-Meier plotter, and PrognoScan - were used in this study. RESULTS Based on the TCGA dataset and Oncomine database, we found that the expression level of FGL2 was remarkably lower in breast cancer compared with adjacent normal tissues. Clinical data showed that the expression level of FGL2 was significantly associated with radiation therapy, PR status, and tumor stage. Bioinformatics analysis of the GEPIA, Kaplan-Meier plotter, and PrognoScan databases showed that lower FGL2 expression levels were associated with a worse prognosis in breast cancer patients. Furthermore, the expression level of FGL2 was positively correlated with the immune cell infiltrations in breast cancer, especially those cells with high antitumor activities. GO, KEGG, and GSEA analyses also validated that FGL2 was closely related to genes involved in the immune response, signal transduction, and T cell receptor signaling pathway in breast cancer. CONCLUSIONS The results demonstrated that high expression of FGL2 is a useful marker for breast cancer treatment and appears to be correlated with enhanced antitumor activities in breast cancer patients.

Chronic gastritis is characterized by inflammation in the gastric mucosa with a vicious circle in inflammatory cells and inflammatory mediators. Stomach adenocarcinoma would occur in the metaplastic gastric mucosa of chronic gastritis. Sijunzi decoction is a famous classical formula for the treatment of chronic gastritis. Although previous studies revealed some functions of Sijunzi decoction in treating chronic gastritis, the underlying mechanisms have not been illustrated clearly. In this study, we used network pharmacology to investigate the mechanism of Sijunzi decoction in treating chronic gastritis. Firstly, online datasets TCMSP, SWISS, and DisGeNET were used to investigate the functional mechanism of Sijunzi decoction against chronic gastritis and 18 genes were identified as targets of Sijunzi decoction in chronic gastritis. These 18 genes can be categorized into immunologically related genes and cancer-related genes. GO analysis showed that the 18 target genes were mainly enriched in angiogenesis, nitric oxide biosynthetic process, ERK1 and ERK2 cascade, cellular response to drug, and MAPK cascade. So, Sijunzi decoction alleviated chronic gastritis by inhibiting the local inflammatory response. Furthermore, we also investigated the impact of Sijunzi decoction on the peripheral blood leukocytes with our own RNA sequencing (RNA-seq) data of 11 chronic superficial gastritis patients. 102 differentially expressed genes (DEGs) were identified by comparing RNA-seq data of chronic superficial gastritis patients with healthy control groups. After performing a functional analysis on 102 DEGs and Sijunzi decoction potential targets and taking the intersection of these pathways, we found that platelet activation, angiogenesis, and pathways in cancer were candidate target pathways regulated by Sijunzi decoction. Thus, Sijunzi decoction also alleviates chronic gastritis by suppressing inflammatory response of peripheral blood leukocytes. Our results showed that Sijunzi decoction can ameliorate the local gastric inflammation and inflammations in peripheral blood leukocytes and might also reduce the incidence of stomach cancer in chronic gastritis.

Lung cancer is the most common malignant tumor, accounting for 25% of cancer-related deaths and 14% of new cancers worldwide. Lung adenocarcinoma is the most common type of pulmonary cancer. Although there have been some improvements in the traditional therapy of lung cancer, the outcome and prognosis of patients remain poor. Lung cancer is the leading cause of cancer-related deaths worldwide, with 1.8 million new cases being diagnosed each year. Precision medicine based on genetic alterations is considered a new strategy of lung cancer treatment that requires highly specific biomarkers for precision diagnosis and treatment. Fibrinogen-like protein 2 (FGL2) plays important roles in both innate and adaptive immunity. However, the diagnostic value of FGL2 in lung cancer is largely unknown. In this study, we systematically investigated the expression profile and potential functions of FGL2 in lung adenocarcinoma. We used the TCGA and Oncomine datasets to compare the FGL2 expression levels between lung adenocarcinoma and adjacent normal tissues. We utilized the GEPIA, PrognoScan and Kaplan-Meier plotter databases to analyze the relationship between FGL2 expression and the survival of lung adenocarcinoma patients. Then, we investigated the potential roles of FGL2 in lung adenocarcinoma with the TIMER database and functional enrichment analyses. We found that FGL2 expression was significantly lower in lung adenocarcinoma tissue compared with adjacent normal tissue. A high expression level of FGL2 was correlated with better prognostic outcomes of lung adenocarcinoma patients, including overall survival and progression-free survival. FGL2 was positively correlated with the infiltration of immune cells, including dendritic cells, CD8+ T cells, macrophages, B cells, and CD4+ T cells, in lung adenocarcinoma. Functional enrichment analyses also showed that a high expression level of FGL2 was positively correlated with enhanced T cell activities, especially CD8+ T cell activation. Thus, we propose that high FGL2 expression, which is positively associated with enhanced antitumor activities mediated by T cells, is a beneficial marker for lung adenocarcinoma treatment outcomes.

SAPHO syndrome is an inflammatory disease invading the skin and bones, whose diagnosis has been difficult due to its low incidence and diversified manifestation. We investigated the serum proteomic profile of SAPHO patients to identify key proteins associated with SAPHO syndrome, trying to find clinical biomarkers or functional molecules for this rare disease. Blood samples from 8 SAPHO patients and 8 healthy controls were detected and analyzed using data independent acquisition (DIA) method to identify differentially expressed proteins (DEPs) specific to SAPHO. A total of 57 differentially expressed proteins were identified (p 0.05, fold change1.2), in which 27 proteins were upregulated and 30 downregulated. DEPs may participate in GO terms such as "lipid particle" and "Notch signaling pathway", as well as KEGG pathways including "complement and coagulation cascades" and "mTOR signaling pathway". The overexpression of inhibitors of the complement system (CFH and C4BP), were verified in a larger cohort (16 SAPHO patients, 8 AS patients and 24 healthy controls) with ELISA, and the combined diagnostic ability of CFH and C4BP was predicted by ROC curve with an AUC of 0.91, which may be molecular candidates for further study on diagnosis and pathology of this rare disease. SIGNIFICANCE: Our research provided the first insight into plasma proteomic profile for SAPHO patients，offering potential biomarkers for disease diagnosis. We found that inhibitors of complement system such as CFH and C4BP were up-regulated in SAPHO syndrome, which may play important roles in the pathogenesis of SAPHO syndrome.

Objective: To screen for blood leukocyte microRNA (miRNA) biomarkers responsible for the association between the traditional Chinese medicine (TCM) qi deficiency constitution (QDC) and the Pi-qi-deficiency syndrome (PQDS) of chronic superficial gastritis (CSG). Methods: Peripheral blood leukocytes were separated from people of two TCM constitutions (balance and qi deficiency) and from CSG patients with PQDS. Total RNA was isolated from the leukocytes and subjected to subsequent high-throughput miRNA sequencing to identify the miRNAs that are specifically and highly expressed in persons of QDC and CSG patients with PQDS. In addition, the target genes of the associated miRNAs were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based enrichment analyses of these target genes were performed to further evaluate the associated miRNA candidates as potential biomarkers responsible for the association between QDC and PQDS of CSG. Results: Compared with the control group with a balance constitution (P 1.5 or

Aim To evaluate the technical feasibility and treatment results of ultrasound (US)-guided percutaneous radiofrequency ablation (RFA) combined with ethanol ablation (EA) for hepatocellular carcinoma (HCC) in the caudate lobe. Materials and methods The institutional review board approved this retrospective study and the requirement for informed consent was waived. From October 2009 to June 2016, there were 49 patients with HCC in the caudate lobe underwent ablation. Among them, 14 patients (12 men and two women, mean age: 49.9±14.9 years) with 16 caudate lobe HCCs (mean size: 3±1.1 cm) who underwent US-guided RFA-EA were identified. These patients were compared with patients who underwent RFA alone (n=17) and EA alone (n=18). Results HCCs in the RFA-EA group were larger than those in the EA-alone group (3±1.1 versus 2.1±0.7 cm, p=0.028). In the RFA-EA group, all the patients achieved treatment success (14/14) and entered follow-up. After a follow-up period of 17.1±10.6 months (range, 5–36 months), local tumour progression (LTP) was detected in four tumours. The 1- and 2-year LTP rates after RFA-EA were 18.8% and 27.8%, respectively. The 1- and 2-year disease-free survival (DFS) rates were 35.7% and 13.4%. Six patients died, with the 1-, 2-, and 3-year overall survival (OS) rates of 85.1%, 63.1%, and 21%, respectively. There were no significant differences in the LTP, DFS, and OS rates between the RFA-EA group and RFA-alone or EA groups (p=0.363–0.733). Conclusion US-guided percutaneous RFA-EA appears to be a feasible and effective treatment for HCC in the caudate lobe.

Background Norovirus is a contagious disease. The transmission of norovirus spreads quickly and easily in various ways. Because effective methods to prevent or treat norovirus have not been discovered, it is important to rapidly recognize and report norovirus outbreaks in the early phase. Internet search has been a useful method for people to access information immediately. With the precise record of internet search trends, internet search has been a useful tool to manifest infectious disease outbreaks. Objective In this study, we tried to discover the correlation between internet search terms and norovirus infection. Methods The internet search trend data of norovirus were obtained from Google Trends. We used cross-correlation analysis to discover the temporal correlation between norovirus and other terms. We also used multiple linear regression with the stepwise method to recognize the most important predictors of internet search trends and norovirus. In addition, we evaluated the temporal correlation between actual norovirus cases and internet search terms in New York, California, and the United States as a whole. Results Some Google search terms such as gastroenteritis, watery diarrhea, and stomach bug coincided with norovirus Google Trends. Some Google search terms such as contagious, travel, and party presented earlier than norovirus Google Trends. Some Google search terms such as dehydration, bar, and coronavirus presented several months later than norovirus Google Trends. We found that fever, gastroenteritis, poison, cruise, wedding, and watery diarrhea were important factors correlated with norovirus Google Trends. In actual norovirus cases from New York, California, and the United States as a whole, some Google search terms presented with, earlier, or later than actual norovirus cases. Conclusions Our study provides novel strategy-based internet search evidence regarding the epidemiology of norovirus.

Objective Neutrophils play an important role in the pathogenesis of rheumatoid arthritis (RA). In this study, we used the adjuvant-induced arthritis murine model to evaluate the efficacy of celastrol on neutrophil-mediated inflammation in RA. Methods Freund's complete adjuvant-induced arthritis was used as the murine model of RA. Celastrol was intraperitoneally administrated daily after onset of the disease. The joint diameter and inflammatory score were evaluated daily during the treatment period. Myeloperoxidase (MPO) and neutrophil elastase (NE) activities were evaluated by immunohistochemical analyses. Quantitative PCR and enzyme-linked immunoabsorbent assay were used to quantify the expression of cytokines. The expression of apoptosis-related proteins Bcl-2, Bax and caspase-3 were evaluated by western blot. Results Celastrol suppressed inflammation in joints of arthritic mice and diminished the expression of MPO and NE in the joint tissue. Celastrol significantly inhibited the expression of TNFα and IL-6 induced by LPS in neutrophils in a dose-dependent manner in vitro . Moreover, celastrol induced apoptosis of LPS-stimulated neutrophils by increasing the expression of Bax and cleaved caspase-3 while decreasing Bcl-2 expression. Conclusion Our findings show that celastrol significantly alleviates murine arthritis by modulating the inflammatory activities of neutrophils. These results indicate that celastrol could serve as an alternative or adjunct modality for the treatment of RA.

Bioactive compounds from medicinal plants with anti-inflammatory and immunosuppressive effects have been emerging as important sources of drugs for the treatment of inflammatory disorders. Triptolide, a diterpene triepoxide, is a pharmacologically active compound isolated from Tripterygium wilfordii Hook F (TwHF) that is used as a remedy for inflammatory and autoimmune diseases. As the most promising bioactive compound obtained from TwHF, triptolide has attracted considerable interest recently, especially for its potent anti-inflammatory and immunosuppressive activities. Over the past few years, an increasing number of studies have been published emphasizing the value of triptolide in the treatment of diverse inflammatory disorders. Here, we systematically review the mechanism of action and the therapeutic properties of triptolide in various inflammatory diseases according to different systematic organs, including lupus nephritis, inflammatory bowel disease, asthma, and rheumatoid arthritis with pubmed and Embase. Based on this review, potential research strategies might contribute to the clinical application of triptolide in the future.

The purpose of this study was to retrospectively compare the imaging features of hepatic epithelioid angiomyolipoma (HEAML) to those of hepatocellular carcinoma negative for hepatitis B surface antigen and hepatitis C antibody (NBNC-HCC) on contrast-enhanced ultrasound (CEUS) with sulphur hexafluoride microbubbles.Twenty-two patients (4 men, 18 women) with a mean age of 42.6±10.2 (SD) years (range: 22-63 years) with histopathologically confirmed HEMAL were included in the study. Forty-four patients (30 men, 14 women) with a mean age of 57.3±15.9 years (range: 19-85 years) with histopathologically confirmed NBNC-HCC were randomly selected from our institution's database as a control group. The CEUS characteristics of the two groups were compared.On conventional ultrasound, significant differences in tumor diameter were found between HEAML (4.0±2.0 [SD] cm; range: 1.3-8.9cm) and NBNC-HCC (8.4±4.4 [SD] cm; range: 1.6-18cm) (P0.001) as well as in degrees of enhancement during the portal (P=0.001) and late phases (P=0.003), contrast distribution (P0.001) and absence of pseudocaspule (P0.001). On CEUS, hyperenhancement during the arterial phase was observed in 21/22 (95.5%) HEAMLs and in 43/44 (97.7%) NBNC-HCCs (P0.999). Homogeneous enhancement was more frequent in HEAMLs (20/22; 90.9%) than in NBNC-HCCs (13/44; 29.6%) (P0.001). Pseudocapsule was observed in 0/22 HEAMLs (0.0%) and in 36/44 NBNC-HCCs (81.8%) (P=0.017). A prolonged enhancement was observed in 5/22 HEAMLs (22.7%) and in 0/44 NBNC-HCCs (0.0%) (P0.001) during the late phase.CEUS with sulphur hexafluoride microbubbles is helpful in discriminating between HEAML and NBNC-HCC. Homogeneous enhancement and lack of pseudocapsule are suggestive features for the diagnosis of HEAML.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis with swelling and pain at synovial joints. In RA patients, delayed neutrophil apoptosis amplifies the inflammatory response and massively released neutrophil extracellular traps (NETs) induce tissue damage and provide self-antigens. Andrographolide (AD) is the major active labdane diterpenoid derived from Andrographis paniculata, which has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. In the present study, we investigated the effect of AD on an adjuvant-induced arthritis (AA) murine model of RA and found that AD alleviated murine arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieved the systematic inflammation. In vitro experiments showed that AD accelerated the apoptosis of lipopolysaccharide-activated neutrophils and inhibited autophagy-dependent extracellular traps formation of neutrophils. These findings suggest that AD has considerable potential for RA therapy.

Ethnopharmacological relevance Fructus gardenia is widely used for treatment of stroke and infectious diseases in Chinese medicine. Geniposide is the key bioactive compound related to the pharmacodynamic actions of gardenia on ischemic stroke. The molecular mechanism by which geniposide improves the ischemic brain injury was observed in the study. Aim of the study Recent studies showed that geniposide had protective activities against the inflammatory response in ischemic stroke. However, the molecular mechanism of geniposide anti-inflammatory role has not yet been fully elucidated. In this study, we investigated the effect of geniposide on the expression of P2Y14 receptor and downstream signaling pathway in brain microvascular endothelial cells (BMECs). Materials and methods An in vitro model of cerebral ischemia in BMECs was established by oxygen-glucose-deprivation (OGD). To further confirm the specific effect of geniposide on P2Y14 receptor and downstream signaling pathways, we set up a UDP-glucose (an agonist of the P2Y14 receptor) stimulated model. After administration of geniposide, the expression of P2Y14 receptor, phosphorylation of RAF-1, mitogen activated protein kinase kinase1/2 (MEK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2), level of interleukin-8 (IL-8), interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1) in BMECs were determined. Results The mRNA and protein expression of P2Y14 in the rat BMECs were up-regulated in OGD-induced injury. After administration of Geniposide, the expression of P2Y14 receptor was significantly down-regulated, the phosphorylation of RAF-1, MEK1/2, ERK1/2 were suppressed. Similar data were obtained in UDP-glc stimulated model. We also observed that geniposide markedly declined the production of IL-8, IL-1β and MCP-1 in OGD-induced BMECs. Conclusion Geniposide exerted anti-inflammatory effects by interfering with the expression of P2Y14 receptor, which subsequently inhibits the downstream ERK1/2 signaling pathways and the release of the pro-inflammatory cytokines IL-8, MCP-1, IL-1β. Therefore, this study provides the evidence for gardenia's clinical application in cerebral ischemia.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by cellular infiltration into the joints and cartilage destruction. Neutrophils play a crucial role in the pathogenesis of RA. Triptolide (TP) is a bioactive compound derived from Tripterygium wilfordii Hook F, which has been used in folk medicine as a treatment for a variety of inflammatory disorders, including RA, for many centuries. Previous studies have shown that TP possesses anti-arthritic activity. However, the anti-arthritic mechanism of TP remains to be fully defined. In the present study, we used the adjuvant-induced arthritis (AA) murine model of RA to investigate the impact of TP on RA and neutrophil function. TP alleviated AA by reducing neutrophil recruitment and suppressing the expression of interleukin-6 and tumour necrosis factor-α in vivo. TP also suppressed the expression of pro-inflammatory cytokines in neutrophils, promoted neutrophil apoptosis and inhibited the migration, NETosis and autophagy of neutrophils in vitro. Based on our findings, TP effectively ameliorates RA by down-regulating neutrophil inflammatory functions, indicating that TP represents a potential therapeutic agent for RA.

Aim To evaluate the relationship between the imaging features of combined hepatocellular–cholangiocarcinoma (CHC) on contrast-enhanced ultrasound (CEUS) and clinicopathological findings. Materials and methods From August 2004 to August 2016, 40 patients (29 males, 11 females; mean age 52.8±11.2 years) with histopathologically proven CHC were investigated. The CEUS imaging features and clinicopathological findings of CHC were analysed and compared retrospectively. Results On CEUS, peripheral irregular rim-like enhancement, diffuse heterogeneous enhancement, and diffuse homogeneous enhancement was illustrated in 13 (32.5%), 21 (52.5%), and six (15%) lesions, respectively. Histopathological findings showed hepatocellular carcinoma (HCC) predominance and cholangiocarcinoma (CC) predominance throughout the tumour were illustrated in 21 (52.5%) and 19 (47.5%) cases, respectively. HCC-predominant CHCs displayed diffuse heterogeneous enhancement more frequently than peripheral irregular rim-like enhancement (p=0.005), whereas CC-predominant CHCs displayed peripheral irregular rim-like enhancement more frequently than diffuse heterogeneous enhancement and homogeneous enhancement (p=0.005 and p=0.01, respectively). CHCs >5 cm displayed diffuse heterogeneous enhancement more frequently than diffuse homogeneous enhancement, whereas CHCs ≤5 cm displayed diffuse homogeneous enhancement more frequently than diffuse heterogeneous enhancement (p=0.004). Conclusion The enhancement pattern of CHC on CEUS depended on the relative proportions of the HCC and CC components and showed size-dependent characteristics.