[Methylated SDC2 testing in stool DNA for early screening of colorectal cancer in Shipai Town, Dongguan City].

Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ2=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.

Effect of different types of sugar on gut physiology and microbiota in overfed goose.

To explored the difference of goose fatty liver formation induced-by different types of sugar from the intestinal physiology and the gut microflora, an integrated analysis of intestinal physiology and gut microbiota metagenomes was performed using samples collected from the geese including the normal-feeding geese and the overfed geese which were overfed with maize flour or overfeeding dietary supplementation with 10% sugar (glucose, fructose or sucrose, respectively), respectively. The results showed that the foie gras weight of the fructose group and the sucrose group was heavier (P < 0.05) than other groups. Compared with the control group, the ileum weight was significantly higher (P < 0.01), and the cecum weight was significantly lower in the sugar treatment groups (P < 0.001). Compared with the control group, the ratio of villi height to crypt depth in the fructose group was the highest in jejunum (P < 0.05); the trypsin activity of the ileum was higher in the fructose group and the sucrose group (P < 0.05). At the phylum level, Firmicutes, Proteobacteria and Bacteroidetes were the main intestinal flora of geese; and the abundance of Firmicutes in the jejunum was higher in the sugar treatment groups than that of the maize flour group. At the genus level, the abundance of Lactobacillus in the jejunum was higher (P < 0.05) in the sugar treatment groups than that of the maize flour group. In conclusion, forced-feeding diet supplementation with sugar induced stronger digestion and absorption capacity, increased the abundance of Firmicutes and Bacteroidetes and the abundance of Lactobacillus (especially fructose and sucrose) in the gut. So, the fructose and sucrose had higher induction on hepatic steatosis in goose fatty liver formation.

Tissue expression of neu differentiation factor/heregulin and its receptor complex in prostate cancer and its biologic effects on prostate cancer cells in vitro.

BACKGROUND: Prostate cancer is the most common cancer in American men and the second leading cause of cancer death. All clinical observations correlate poorly differentiated high-grade prostate cancer with disease-specific mortality. The HER2 cell membrane tyrosine kinase, a member of the epidermal growth factor receptor family that is the transcription product of the erbB2neu oncogene, and HER3, a receptor protein of the same family, are overexpressed in prostate cancer and prostatic intraepithelial neoplasia. The ligand for these receptors and another related family member, HER4, has recently been identified by independent investigator groups and called neu differentiation factor (NDF) or heregulin. In vitro treatment of HER2- and HER3- or HER2- and HER4-expressing breast cancer cells stimulates tyrosine phosphorylation of HER2 and produces changes in the rate of proliferation, degree of cellular differentiation, and synthesis of physiologic secretion products. There are no published reports on the expression of NDF and HER4 in prostate cancer or the in vitro effects of NDF in prostate cancer cells. METHODS: Expression of NDF, HER2, HER3, and HER4 was studied in 24 frozen prostatectomy specimens by immunohistochemistry. The biologic effect of human recombinant NDF was studied in vitro, using the LNCaP, PC3, and DU145 human prostate cancer cell lines. HER and NDF protein expression was studied by immunohistochemistry. NDF mRNA was analyzed using reverse transcriptase polymerase chain reaction from whole RNA. The biologic effects of NDF on prostate cancer cells in vitro included cell proliferation, thymidine synthesis, induction of prostate-specific antigen mRNA, anchorage-dependent and anchorage-independent cell growth, and ploidy analysis. Data analysis was performed using Student's t test. RESULTS: Observations in clinical prostatectomy specimens: Immunohistochemistry studies in clinical prostatectomy specimens demonstrate absence of significant NDF expression in prostate cancer, whereas it is expressed in 100% of the stroma, 100% of basal epithelial cells, and 58% of luminal cells in normal and benign hyperplastic prostatic tissue. The HER4 receptor protein is strongly expressed by normal prostate luminal cells, but not prostate cancer. Benign prostate tissue exhibits strong expression of HER2, HER3, and HER4 by basal cells, but only luminal cells significantly express HER4. Only 23% of prostate cancer specimens express HER4, while 95% express HER3 and 82% HER2. Prostatic intraepithelial neoplasia stained similarly to cancer for all proteins studied. Observations in prostate cancer cell lines: In vitro treatment with NDF significantly reduces aneuploidy and proliferation and growth of androgen-sensitive prostate cancer cells. Incubation with NDF also induces prostate-specific antigen mRNA in prostate cancer cells. In spite of displaying NDF mRNA, prostate cancer cells do not produce detectable NDF protein, but express HER2 and HER3 proteins. DISCUSSION: These data suggest that NDF may be a paracrine differentiation factor involved in normal adult prostate physiology and that functional loss of the NDF/HER ligand/ receptor loop may be an early event associated with prostate tumorigenesis.

Significance of anti-nuclear matrix antibodies in patients with in vivo speckled antinuclear antibody staining.

OBJECTIVE: Evidence suggests that patients with in vivo speckled antinuclear antibody (ANA) patterns have high titers of circulating ANA, specifically anti-U1 RNP antibody. A small percentage of patients with high titers of anti-U1 RNP antibody have anti-nuclear matrix antibodies, and some also demonstrate in vivo ANA. This study was designed to screen for the presence of anti-nuclear matrix antibodies in patients with in vivo ANA. METHODS: Anti-nuclear matrix antibodies were detected by indirect immunofluorescence on HCI-extracted HEp-2 cell substrate, by enzyme-linked immunosorbent assay, and by immunoblot analysis. RESULTS: All 10 patients with in vivo ANA were found to have anti-nuclear matrix antibody demonstrated using HCI-extracted HEp-2 cell substrate, and all exhibited antibody activity to a 36-kd protein from nuclear matrix antigen. CONCLUSION: These results suggest that anti-nuclear matrix antibodies are a major factor in the development of in vivo ANA.

Antigen retrieval in immunofluorescent testing of bullous pemphigoid.

Direct immunofluorescence is an immunopathological technique frequently utilized for diagnosis of vesiculobullous disease such as bullous pemphigoid. Fresh-frozen tissue is required for immunofluorescent testing, making retrospective analysis difficult. In this study, we compared two methods of antigen retrieval in formalin-fixed, paraffin-embedded skin tissue from patients with bullous pemphigoid to determine if archival tissue, after use of an unmasking antigen, can be substituted for fresh-frozen tissue in the immunopathological study of skin. Paraffin-embedded tissue blocks from patients with bullous pemphigoid and patients with eosinophilic spongiotic dermatitis as the prodromal stage of bullous pemphigoid were obtained. Sections were mounted on poly-L-lysine-coated slides and the slides were deparaffinized. The methods of antigen retrieval included incubation with trypsin (0.1%) and microwave irradiation in urea (6 M). Antigen retrieval was followed by indirect immunofluorescence. Microwave irradiation was more effective in antigen retrieval than was incubation with trypsin (0.1%). Microwave irradiation in urea (6 M) produced more intense immunofluorescent staining than did trypsinization. Overall, positive basement membrane zone immunofluorescent staining was found in 60% of patients with a diagnosis of classical bullous pemphigoid and in 50% of patients with eosinophilic spongiotic dermatitis as the prodromal stage of bullous pemphigoid. Although the frozen-tissue method appeared more effective than the antigen-retrieval method in immunofluorescent testing of skin, the antigen-retrieval method can certainly be considered an option in retrospective studies. Antigen retrieval may be particularly advantageous in patients with eosinophilic spongiotic dermatitis in whom the diagnosis of bullous pemphigoid may not be suspected initially.