Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes (T2DM). Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge. Neutral sphingophospholipase 2 (Smpd3) is downregulated in jawbone-derived bone marrow mesenchymal stem cells (BMSCs) from T2DM patients. Here, we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles. The combined loading of Smpd3-overexpressing stem cell-derived exosomes (Exos-Smpd3) and nanosilver ions (Ns) to construct a hydrogel delivery system (Exos-Smpd3@Ns) promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment, ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro. Mechanistically, Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations. These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations, providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.
Exosomes ; Animals ; Bone Regeneration/drug effects* ; Dogs ; Mesenchymal Stem Cells ; Humans ; Blood Glucose ; Cell Differentiation ; Osteogenesis/drug effects* ; Diabetes Mellitus, Type 2/therapy* ; Diabetes Mellitus, Experimental ; Cells, Cultured ; Hydrogels ; Male

Objective To investigate the clinical and pathological features of patients with colorectal lesions, which could be the basis for clinical diagnosis and treatment of early colorectal cancer. Methods The clinical ( including gender, age, size, location, morphology, and number ) and pathological characteristics of colorectal lesions were discussed based on the results of colorectal cancer screening in more than 320000 people of 40-74 years in Haining from 2007 to 2012. Results Screening of 286470 cases were completed with the compliance rate of 88. 96％. Colonoscopy was performed in 29069 cases, and 7408 lesions were detected with detection rate of 25. 48％. The detection rate was 32. 62％ for men and 19. 48％ for women ( P<0. 001 ) , and 18. 30％ in 40-49 age group and 35. 06％ in 70-74 age group. The older the patients, the higher the detection rate ( P<0. 001) . Among the 7408 lesions, left colonic lesions accounted for 69. 40％, multiple lesions accounted for 37. 23％, lesions with diameter>1. 0 cm accounted for 19. 60％. A total of 205 cases of colorectal cancer ( including 161 early carcinoma and 44 advanced carcinoma) , and 1365 cases of advanced adenoma were found. The early diagnosis rate was 97. 20％. Among the 5030 lesions underwent treatment, adenomatous and carcinomatous types accounted for the largest proportion ( 63. 00％) . The canceration rate of lesions with diameter >1. 5 cm was 34. 08％. Conclusion In high-risk populations, men have a higher detection rate of colorectal lesion than female. The older the age, the higher the detection rate. Adenoma account for the highest proportion among different pathologic types.

Objective To investigate the application effects of quantitative and qualitative fecal occult blood (FOB) reagent in colorectal cancer screening.Methods With the platform of colorectal cancer screening for early diagnosis and treatment,the original screening methods and process were not changed,individuals underwent colorectal cancer screening,aged from 40 to 74 years old,from four villages of Haining City in Zhejiang Province were selected as study objects.Initial screening included medical history questionnaire and FOB test.The first stool samples were examined both with quantitative and qualitative FOB test,one week later the second samples were detected with qualitative FOB test.History positive or once of any type of reagent positive was considered as initial screening positive.The individuals with initial screening positive received fine screening (colon endoscope examination).The effects evaluation included the positive rate of FOB,intestinal lesion detection rate,sensitivity,specificity and Youden index.The health economic analysis was calculated.Chi-square test was performed for comparisons between the two groups.Results A total of 8 427 history survey were completed,the positive rate of history was 8.48％(715/8 427) ; 6 644 underwent quantitative detection of FOB and the positive rate was 4.44 ％ (295/6 644) ; qulitative test was conducted in 12 633 samples were conducted and the positive rate was 2.56 ％ (324/12 633),the difference was statistically significant (x2 =49.27,P＜ 0.01).A total of 854 individuals with initial screening positive underwent electronic colonoscopy examination,the total intestinal lesion detection rate was 22.72％ (194/854),of which the intestinal lesion detection rate of quantitative group was 34.55％ (66/191),and that of qualitative group was 17.73％ (36/203),the difference was statistically significant (x2 =14.53,P＜0.01).The detection rate of both quantitative and qualitative test positive was 43.75 ％ (14/32).The colorectal cancer detection rates of quantitative and qualitative FOB test were 3.66％ (7/191) and 0.99％ (2/203),advanced adenoma detection rates were 8.38 ％ (16/191) and 5.91％,there were no significant differences (x2 =2.08 and 0.96,both P＞0.05).The sensitivity of quantitative and qualitative FOB test in advanced adenoma and cancer detection rate was 45.10％ and 27.45％,respectively.The average cost of quantitative and qualitative FOB test in intestinal lesions detection was 5 874.50 and 1 432.14 yuan.Conclusion The effects of quantitative FOB test in colorectal cancer screening was better than that of qualitative reagent,however on the cost of screening,the former was 4.10 times of the latter.