Objective: To evaluate the relationship between contrast-enhanced ultrasonography (CEUS) of carotid intraplaque neovascularization and ischemic stroke in transient ischemic attack (TIA) patients. Methods: A total of 112 TIA patients were selected for the study. Routine carotid ultrasonic examination was performed for all the patients. CEUS was carried out for consecutive patients with plaque thicker than 2.5 mm in carotid bifurcation and follow-up for at least 24 months. The number of patients with incurrence of ischemic stroke or recurrence of TIA was obtained during the follow-up period. To detect the risk factors for incurrence of ischemic stroke or recurrence of TIA in 24 months, multivariate logistic regression analyses were performed for all the risk factors in all the selected patients. Results: Ninety-one patients underwent CEUS and were followed up at least 24 months. There were statistical differences between recurrent and non-recurrent groups about hypertension, diabetes, hyperlipemia, smoking history, family history of stroke, medication compliance, two-dimensional ultrasound, and CEUS ( P < 0.05). The higher CEUS intensity in the carotid plaque was, the higher was the possibility of ischemic stroke or recurrent TIA. Multivariate logistic regression analysis showed that the CEUS characteristics of carotid plaque such as linear enhancement or diffuse enhancement were independent risk factors for ischemic stroke or recurrent TIA in TIA patients ( P < 0.05). Conclusion: For carotid plaques, CEUS could evaluate the infusion mode, which could reflect the neovascularization in plaques. CEUS could predict the incurrence of ischemic stroke or recurrence of TIA in TIA patients, which is useful information when making a clinical decision.

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Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla , in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

The seven-amino acid truncated (7ND) protein is an N-terminal deletion mutant of monocyte chemoattractant protein-1 (MCP-1) and it functions as a dominant-negative inhibitor. 7ND and wild-type MCP-1 form a heterodimer, which binds to MCP-1 receptors and inhibits monocyte chemotaxis. In the present study, the 7ND protein was cloned, expressed and purified. An MTT assay revealed that the proliferation of oral squamous cell carcinoma (OSCC) SCC25 cells was not affected following 3 days of treatment with synthetic 7ND protein. Serial dilutions of the 7ND protein were tested for monocyte migration and osteoclast differentiation, and tartrate-resistant acid phosphatase staining demonstrated that significantly fewer osteoclasts were differentiated from cluster of differentiation 14+ (CD14+) monocytes using magnetic activated cell sorting. Immunofluorescence confirmed these results and significantly less F-actin staining was observed in 7ND-treated osteoclasts. Furthermore, bone invasion was examined by subcutaneously injecting SCC25 cells into the area overlaying the calvariae of nude mice. The results demonstrated that the average tumor volume of SCC25 cells with 7ND protein was similar to the average volume of tumors formed by untreated SCC25 cells. Flow cytometric analysis suggested that the CD14+ subpopulation in the bone marrow of 7ND-treated mice was reduced compared with that of untreated mice. Micro-computed tomography imaging revealed significantly less bone resorption in the calvariae injected with SCC25 cells plus the 7ND protein. Taken together, the results of the present study demonstrated the potential therapeutic value of the 7ND protein. The 7ND MCP-1 variant not only functions in vitro to inhibit osteoclast differentiation, but also reduces the progression of bone invasion by OSCC cells in vivo.

Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.