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Background: Acute pancreatitis is a severe pancreatic disorder that remains associated with high mortality due to a lack of effective drugs and management strategies. This study aimed to investigate the molecular pathogenic mechanisms of acute pancreatitis involving p53 and endoplasmic reticulum (ER) stress pathways. Methods: Expression of PRSS1 and p53 in human acute pancreatitis tissues was detected by immunohistochemistry and western blotting. Acute pancreatitis was induced with caerulein in humanized PRSS1 transgenic mice, and its severity was verified by histological imaging, evaluation of edema, and serum amylase and trypsin activity assays. A transferase mediated d-UTP nick end-labeling assay was performed to evaluate acinar cell apoptosis associated with acute pancreatitis. The expression of ER stress genes was assessed by quantitative RT-PCR (qRT-PCR) and western blotting. Results: PRSS1 and p53 were highly expressed in human acute pancreatitis tissues. Expression of human PRSS1 in caerulein-treated mice induced significant acinar cell apoptosis and acute pancreatitis progression. p53 knockout significantly aggravated acute pancreatitis progression in humanized PRSS1 transgenic mice. The ER stress pathway was activated by PRSS1 and mediated the progression of acute pancreatitis in mouse pancreatic tissues. Application of a p53 inhibitor promoted caerulein-induced acute pancreatitis in PRSS1 transgenic mice, while a p53 activator ameliorated the progression of acute pancreatitis. Conclusion: P53, which was activated by the ER stress pathway, suppresses the progression of acute pancreatitis in mice expressing PRSS1 by inducing acinar cell apoptosis. Funding: The article is supported by Scientific Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (CX2018N012) & Clinical Research Program of Nanfang Hospital, Southern Medical University (2018CR046) & Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2016PY011). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: All experimental procedures performed with mice were approved by the Institutional Animal Care and Use Committee of Southern Medical University.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with an increasing incidence. Aberrant activation of the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is common in human cancers and has been revealed to play an important function in cell proliferation, metabolism and tumorigenesis. In the present study, NVP-BEZ235, a dual PI3K/mTOR inhibitor, was revealed to be effective in inhibiting proliferation and inducing cell cycle arrest in MKL-1 cells. Additional investigations revealed that NVP-BEZ235 attenuated PI3K/Akt/mTOR signaling and upregulated the levels of the cell cycle inhibitors p21 and p27. Overall, the present results possess considerable implications for future development of dual PI3K/mTOR inhibitor as potential agents in the management of MCC.

Concrete-filled L-shaped steel tube columns can be used to save architectural space at room corners, and may have many advantages of structural behavior of common concrete-filled steel tubes as columns. In this paper, the seismic behavior of concrete-filled L-shaped steel tube columns (CFLSTs) was investigated. Six specimens subjected to a constant axial load and cyclically varying lateral loading were tested to study the effects of width to depth ratio of section, depth to thickness ratio of steel tube and axial load level on the strength, as well as stiffness, ductility and energy dissipation of CFLST columns. Experimental results showed that the displacement ductility of CFLST columns decreased significantly with the increase of axial load level, and the strength and stiffness degradations of CFLST columns were more significant with higher axial load level. With the increase of depth-thickness ratio of steel tube and depth-width ratio of section, the ductility and the lateral ultimate load-carrying capacity of CFLST columns also decreased gradually. All CFLST columns exhibited favorable energy dissipation and ductility, even for the columns subjected to high axial load, which indicates that this type of composite columns is adoptable in practical engineering, especially in seismic regions.

Bone morphogenetic proteins (BMPs) play an important role in regulating osteoblast differentiation and subsequent bone formation, mainly evidenced by the induced osteogenic ability of BMP-2 from BMPs. However, BMP-2 alone does not induce the expected efficacy due to its short retention in vivo. In this study, a novel BMP-2-related peptide (designated P24) derived from the “knuckle epitope” of BMP-2 was coupled covalently to type I collagen derived from rat tail and observed under scanning electron microscopy (SEM) in low vacuum mode. The BMP-2-related peptide/collagen composite was implanted in vivo into the pocket of the quadriceps musculature of Sprague-Dawley (SD) rats and then harvested 3 or 6 weeks after surgery. It was found that lyophilized collagen retained a porous network structure with an average inner-diameter of 90 ∼ 160 μm. Based on radiographic evaluation and histological examination, BMP-2-related peptide/collagen induced significant ectopic bone formation compared to that of rat tail collagen alone as a control. Our results indicate collagen served as a good carrier for newly synthesized BMP-2-related peptide and that the BMP-2-related peptide/collagen composite was an effective substitute in bone tissue engineering.

BMP-2 is one of the most important growth factors of bone regeneration. Polylactide-co-glycolic acid (PLGA), which is used as a biodegradable scaffold for delivering therapeutic agents, has been intensively investigated. In previous studies, we synthesized a novel BMP-2-related peptide (designated P24) and found that it could enhance the osteoblastic differentiation of bone marrow stromal cells (BMSCs). The objective of this study was to construct a biomimetic composite by incorporating P24 into a modified PLGA-(PEG-ASP)n copolymer to promote bone formation. In vitro, our results demonstrated that PLGA-(PEG-ASP)n scaffolds were shown to be an efficient system for sustained release of P24. Significantly more BMSCs attached to the P24/PLGA-(PEG-ASP)n and PLGA-(PEG-ASP)n membranes than to PLGA, and the cells in the two groups subsequently proliferated more vigorously than those in the PLGA group. The expression of osteogenic markers in P24/PLGA-(PEG-ASP)n group was stronger than that in the PLGA-(PEG-ASP)n and PLGA groups. Radiographic and histological examination, Western blotting and RT-PCR showed that P24/PLGA-(PEG-ASP)n scaffold could induce more effective ectopic bone formation in vivo, as compared with PLGA-(PEG-ASP)n or gelatin sponge alone. It is concluded that the PLGA-(PEG-ASP)n copolymer is a good P24 carrier and can serve as a good scaffold for controlled release of P24. This novel P24/PLGA-(PEG-ASP)n composite promises to be an excellent biomaterial for inducing bone regeneration.

The factors influencing the incidence of common complications (pneumothorax and pulmonary hemorrhage) of CT-guided percutaneous needle biopsy of lumps near pulmonary hilum were investigated. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum was performed on 48 patients. The complications of pneumothorax and pneumorrhagia as well as the contributing factors were analyzed statistically. The major complications associated with CT-guided needle biopsy included pneumothorax (13 cases, 27.1%) and pulmonary hemorrhage (14 cases, 20.24%). χ(2) test revealed that pneumothorax was associated with the lesion size and depth of needle penetration, and pulmonary hemorrhage with the depth of needle penetration and needle retention time with a significant P value. Pneumothorax was observed in 7 cases (17.5%) out of 40 cases with diameter of mass greater than 3 cm, and in 6 cases (60%) out of 10 cases with depth of needle penetration greater than 4 cm. Additionally, pulmonary hemorrhage was identified in 12 cases (41.4%) out of 29 cases with needle retention time longer than 15 min, and pulmonary hemorrhage in 7 cases (70%) out of 10 cases with depth of needle penetration greater than 4 cm. CT-guided percutaneous needle biopsy of lumps near pulmonary hilum is safe and effective. The key factors to prevent the complications include correct evaluation of lesion size, depth of needle penetration and the needle retention time before the operation.