Diabetic nephropathy is a major complication facing patients with diabetes mellitus. The renal protective effects of the phosphodiesterase III inhibitor, cilostazol, were investigated in rats with streptozotocin-induced diabetes. Expression of thrombospondin-1 (TSP-1) and transforming growth factor-b (TGF-b) in the kidney was measured by immunohistochemistry and real-time reverse transcription-quantitative polymerase chain reaction analysis in diabetic rats, cilostazol-treated diabetic rats and control rats. Ultrastructural changes in the kidney were also analysed using microscopy. Four weeks after the induction of diabetes, TSP-1 and TGF-b expression was significantly increased in the kidneys of diabetic rats compared with the control and was significantly lower in cilostazol-treated diabetic rats than in the untreated diabetic rats. Microscopy revealed characteristic renal pathology in the diabetic group, which was rarely seen in the cilostazoltreated diabetic rats. In conclusion, this study indicates that cilostazol treatment of diabetic rats effectively prevents pathological kidney changes, possibly via the down-regulation of TSP-1 and TGF-b expression compared with untreated rats.

Objective Artery calcification, as subclinical atherosclerosis, is attracting attention. The aim of this study was to determine the prevalence and risk factors of artery calcification in patients with systemic lupus erythematosus. Methods 641 patients with systemic lupus erythematosus were enrolled in the study. Demographic, clinical, and laboratory characteristics were collected. Calcification score was quantified from the multi-detector computed tomography scan image using the Agatston Score method. Results The total incidence of artery calcification was 25.9% (166/641), of which the percentages of aorta calcium and coronary artery calcification were 23.1% (148/641) and 8.4% (54/641), respectively. In multivariate models, systemic lupus erythematosus patients with artery calcification had longer disease duration than patients without artery calcification ( p < 0.05). Presence of serositis (OR 2.559, 95%CI 1.414–4.632), pneumonia (OR 2.022, 95%CI 1.102–3.711) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (OR 1.049, 95%CI 1.004–1.095) were independently associated with increased risk of aorta calcium, while the duration of corticosteroids use (OR 1.039, 95%CI 1.002–1.078) and cyclophosphamide therapy (OR 8.251, 95%CI 2.496–27.279) were independently associated with increased risk of coronary artery calcification in systemic lupus erythematosus patients. In systemic lupus erythematosus patients, aorta calcium was prone to occur at a younger age compared to coronary artery calcification, and aorta calcium score was positively correlated with age. Conclusions Systemic lupus erythematosus patients had a much earlier onset and higher incidences of aorta calcium than coronary artery calcification. Presence of serositis, pneumonia, and higher SLEDAI score may predict increased risk of aorta calcium.

Background Crohn’s disease (CD) is a heterogeneous and complicated condition that often has delayed diagnoses and poor outcomes. Disease location and site-specific mechanisms have received increasing attention in recent studies. Suboptimal classification adds complexity to clinical management for CD and the interpretation of its characteristics. This study aims to clarify the clinicopathological characteristics of CD patients through a prospective cohort. Methods The clinical data from 1173 patients with definite CD diagnoses and a simplified location classification based on anatomical traits (G1: esophagus+stomach+duodenum; G2: jejunum+ileum; G3: ileocecum; G4: colon+rectum) were used to clarify the feature patterns (Figure 1). Results Of the enrolled patients, 437 were newly diagnosed, and 736 were prevalent patients. A higher proportion of L4 involvement (45.8%) and a lower proportion of L2 (6.8%) patients were observed under the Montreal location classification. Single G2 (17.8%), G2+G3 (22.2%), G3+G4 (12.5%) and G2+G3+G4 (27.8%) were the four major types in the simplified location classification (Figure 2A-2B). The patients with G4 presented with higher C-reactive protein, G2 patients had more stricturing/penetrating behavior, and single G2 patients had the oldest age at diagnosis (Table 1). A clinicomic study with machine learning methods including principal component analysis, cluster analysis and partial least squares discriminant analysis, identified hemoglobin, platelet count and C-reactive protein as the three key indicators. A decision tree based on the three indicators and disease behavior stratified all patients into six feature patterns (simply/complicatedly active, simply/complicatedly anemia and simply/complicatedly stable), which formed a two-twisted-cycle model for natural disease history (Figure 2C). Most patients started their cycles at the active phase, and the “simply” cycle was mainly advanced by medications, while most patients in the “complicatedly” cycle needed multidisciplinary care. Comparisons among the six subgroups showed that age at diagnosis had the same rise-and-fall pattern as the G2+G4- proportion, while the G2-G4+ proportion showed the opposite trend (Table 2, Figure 2D-2E). An external validation group (n=301) confirmed the above results. The role of disease location could be interpreted as an important factor determining its start point and site-specific trajectory in the two-twisted-cycle model. Conclusion Site-specific clinical characteristics clarified by the simplified location classification, the new feature patterns profiled by the clinicomic study may provide new insights into CD phenotyping, risk stratification and precision treatment.

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