OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

Based on the characteristics of forensic pathology, this paper explains the concept, connotation and advantages of holistic medicine and integrated medicine in the teaching of forensic pathology. Then, through the introduction of the specific teaching process design and effect analysis of the death cause analysis practical cases, it clarifies the necessity and effectiveness of integrated medicine and holistic medicine in the teaching of forensic pathology, and provides new ideas for the reform of the overall teaching of forensic pathology.

Causes analysis of death is the most common work in forensic pathology practice. When designing problem-based learning (PBL) teaching objectives, we should take cause analysis of death as the main line and give consideration to other related issues. The selected cases should be typical ones that solve the target problems, which can fully reflect the basic theoretical knowledge of forensic pathology, and have moderate difficulty, delights and clear conclusions. The PBL course is divided into three steps. The first step focuses on providing students with case information to guide them to find out the problems that need to be solved. The second step focuses on discussing the problems and making pathological diagnoses. The third step focuses on answering the question raised at the beginning of the course. Each lesson can also be divided into several sections by which the lesson plans should be prepared. In the teaching process, performing active interaction with students, controlling the direction of classroom development, balancing student opportunities should be done well in order to make the curriculum smoothly and achieve the purpose of teaching.

AIM: To observe the changes in infiltrating macrophages (M?)and extracellular matrix (ECM) in the kidney in the progressive course of nephrotoxic nephritis (NTN). METHODS: NTN model was established with rabbit-anti-rat nephrotoxic serum. On day 3, 7, 15, 30 and 90, renal biopsies were performed. Renal histology was checked under light microscopy with HE and Masson's trichrome staining sections. M?, fibronectin (FN), type Ⅲ and Ⅳ collagen were examined with immunohistochemistry ABC method. RESULTS: Infiltration of M? appeared on day 3 of NTN and preceded changes of FN and collagen. On day 15 of NTN, all nephritic animals had significant proteinuria, increased serum creatinine, infiltration of M? and deposit of entracellular matrix. On day 90 of NTN, seven nephritic animals improved significantly, while other five developed renal scarring with diffuse infiltration of M? which positively paralleled to renal function and deposit of FN, type Ⅲ and Ⅳ collagen. CONCLUSION: M? infiltrating into renal tissue enhances deposit of ECM and therefore plays important roles in progression or improvement of NTN.

AIM: To observe the expression of transforming growth factor ? 1 (TGF-? 1), MAPK 1/3 and fibronectin (FN) in the development of renal tubulointerstitial disease. METHODS: Wistar male rats were randomly divided into normal control group, diabetic group of 1week, 2 weeks, 4 weeks and 8 weeks. Diabetic model was induced by peritoneal injection of streptozotocin. Immunohistochemistry was employed to detect the expression of TGF-? 1, MAPK 1/3 and FN in the kidney. TGF-? 1 protein in the renal cortex was checked by Western blot. BG, Scr and UP were analysed by biochemical methods, and the morphological changes in renal tubulointerstitium were also examined under microscopy on sections stained with HE and PAS. RESULTS: The expression of MAPK 1/3 and FN was observed, but not the expression of TGF-? 1 in normal renal tissue. Positive staining of TGF-? 1 was observed in the renal tubulo-interstitium in 1-week diabetic group and thereafter it increased in the course of diabetes. A continuous increase in the expression of MAPK 1/3 and FN was also observed in two - week diabetic rats. Chronologically the expression of TGF-? 1,MAPK 1/3 and FN and the ratio of KW/BW were positively correlative with each other in diabetic animals except one -week diabetic rats. There was also a positive correlation between MAPK 1/3 and FN in l -week diabetic rats. CONCLUSION: Our data suggest that TGF-? 1 appears in the renal tubulointerstitium in early period of diabetes and then its signal is mediated by MAPK 1/3 cascades to accelerate production of FN ,and in turn leads to renal hypertrophy and tubulointerstitial fibrosis. [