Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

Long non-coding RNA LINC01347 suppresses trophoblast cell migration, invasion and EMT by regulating miR-101-3p/PTEN/AKT axis.

Recurrent miscarriage (RM) is one of the common complications of pregnancy, which is closely related to gene mutation. The profiling of non-coding RNAs showed that the expression level of long non-coding RNA LINC01347 (LINC01347) in the serum of patients with recurrent abortion was significantly increased, which could serve as a potential marker for early diagnosis. However, the biological functions of LINC01347 in the miscarriage remain to be elucidated. In this study, LINC01347 expression levels in HTR-8/SVneo cells and placenta samples were measured by RT-qPCR. The migration ability of HTR-8/SVneo cells was detected by wound-healing assay. Western blotting (WB) assay was conducted to measure E-cadherin, Vimentin, N-cadherin, PTEN, phospho-AKT(S473), phospho-AKT(T308) and AKT levels. Dual luciferase reporter assay and RNA pull-down analysis were performed to validate the molecular interactions. The results showed an upregulation of LINC01347 in the placenta samples of RM patients and HTR-8/SVneo cells. LINC01347 overexpression impaired the invasion and migration of trophoblast cells, while LINC01347 silencing promoted cell migration and invasion. LINC01347 level was also negatively correlated with the changes of epithelial-mesenchymal transition (EMT) markers in trophoblasts. We further demonstrated that miR-101-3p/PTEN/AKT axis played an important role in mediating the biological roles of LINC01347 in the invasion and migration of trophoblasts. In conclusion, our results revealed that LINC01347 suppresses the migratory ability and regulates the EMT processes in trophoblasts by regulating miR-101-3p/PTEN/AKT axis, suggesting that targeting LINC01347 may serve as a strategy to ameliorate RM.

Knockdown of lncRNA ACTA2-AS1 reverses cisplatin resistance of ovarian cancer cells via inhibition of miR-378a-3p-regulated Wnt5a.

Cisplatin (DDP) resistance is a principal cause leading to poor prognosis in females suffering from ovarian cancer (OC). Long non-coding RNA (lncRNA) has been shown to have an involvement in regulating cellular processes; chemoresistance being one of them the precise object of this work was to probe into the role of lncRNA ACTA2-AS1 in OC cells that have developed DDP resistance. We developed DDP-resistant OC cell lines (A2780/DDP and SKOV3/DDP). The influence of the ACTA2-AS1/miR-378a-3p/Wnt5a axis on DDP chemoresistance of DDP-resistant OC cells was ascertained using real-time PCR, Elisa, and CCK-8, and dual-luciferase reporter assay. In DDP-resistant cells and tissues, ACTA2-AS1 was increased, while a substantial downregulation in miR-378a-3p was noticed. In cells manifesting DDP-resistance, knocking down ACTA2-AS1 boosted the expression of miR-378a-3p. Further research into the mechanism of ACTA2-AS1 revealed that it acted as a 'sponge' by getting involved in a competition against miR-378a-3p binding to modify its target Wnt5a. The suppression of DDP-resistance in OC cells caused by ACTA2-AS1 downregulation was reversed by silencing miR-378a-3p. Furthermore, via inhibition of Wnt5a, miR-378a-3p alleviated DDP resistance in OC cells. These findings show that for miR-378a-3p, ACTA2-AS1 works like a sponge thus preventing it from binding to Wnt5a and boosting OC cell DDP resistance. Our research will aid the expansion of plausible therapeutic options for treating OC.

circ_ZFR Is Linked to Paclitaxel Resistance in Cervical Cancer via miR-944 Sponging and IL-10 Upregulation.

OBJECTIVE: Cervical cancer (CC) has an elevated rate of invasion and death despite surgical treatment, radiotherapy, and chemotherapy. Several studies revealed that circRNAs have a key contribution to the resistance of drugs against different types of carcinomas. The goal of the existing study was to figure out what role circ_ZFR plays in paclitaxel (PTX) resistance in cervical cancer (CC) patients. MATERIALS AND METHODS: Herein, two types of CC cells (SiHa/PTX and Hela/PTX) were utilized. The levels of IL-10 mRNA, miR-944, and circ_ZFR were measured using qRT-PCR analyses. The CCK-8 assay was used to determine PTX resistance. The IL-10 expression was measured via the ELISA technique. The combination of miR-944 and circ_ZFR or IL-10 was validated using a dual-luciferase reporter (DLR) assay. RESULTS: The amount of circ_ZFR was increased in PTX-resistant CC cells and tissues. In PTX-resistant CC cells, knocking down circ_ZFR expression decreased PTX resistance. circ_ZFR knockdown significantly reduced IL-10 expression via sponging miR-944, increasing PTX sensitivity in PTX-resistant CC cells. CONCLUSION: circ_ZFR knockdown has a considerable role in overwhelming CC-associated PTX resistance by modifying the axis of miR-944/IL-10 axis, suggesting that developing a circRNA target-based treatment could be considered prevent CC progression.

ZBTB24 (Zinc Finger and BTB Domain Containing 24) prevents recurrent spontaneous abortion by promoting trophoblast proliferation, differentiation and migration.

Recurrent spontaneous abortion (RSA) is a common complication during early gestation, which is associated with aberrant DNA methylation. Zinc Finger and BTB Domain Containing 24 (ZBTB24) plays a critical role in facilitating DNA methylation and cell proliferation. However, the regulatory role of ZBTB24 on trophoblast development in RSA remains unclear. In this study, ZBTB24 expression was compared between decidua tissues of RSA patients and induced abortion controls from a published dataset, which was further validated in placental villi tissues by RT-qPCR and Western blot. The roles of ZBTB24 in trophoblast proliferation, differentiation, and migration were investigated by functional assays after ZBTB24 knockdown or overexpression in HTR-8/SVneo cells. Our results showed that ZBTB24 expression was significantly decreased in RSA patients, and ZBTB24 expression level positively regulated cell viability, differentiation, and migration in HTR-8/SVneo cells. We further demonstrated that ZBTB24 modulated the expression of E-cadherin by altering the DNA methylation at the promoter region. Overall, the downregulation of ZBTB24 is implicated in RSA by inhibiting trophoblast proliferation, differentiation, and migration. Therefore, ZBTB24 may serve as a promising therapeutic target and diagnostic marker for RSA.

Impact of 9-Minute Withdrawal Time on the Adenoma Detection Rate: A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Although current quality indicators of colonoscopy recommend 6 minutes as the minimum standard for withdrawal time (WT), the impact of a WT longer than 6 minutes on neoplasia detection is unclear. METHODS: A multicenter randomized controlled trial involving 1027 patients was conducted from January 2018 to July 2019. Participants were randomly divided into a 9-minute (n = 514) and 6-minute (n = 513) WT group, and a timer was used to adjust the withdrawal speed. The primary outcome was the adenoma detection rate (ADR). RESULTS: Intention-to-treat analysis showed a significantly higher ADR in the 9-minute versus 6-minute WT group (36.6% vs. 27.1%, P = .001). Prolonging WT from 6 to 9 minutes significantly increased ADR of the proximal colon (21.4% vs. 11.9%, P < .001) as well as of the less experienced colonoscopists (36.8% vs. 23.5%, P = .001). Improvements were also observed in the polyp detection rate (58.0% vs. 47.8%, P < .001), and mean number of polyps and adenomas detected per colonoscopy (1.1 vs. 0.9, P = .002; 0.5 vs. 0.4, P = .008, respectively). The higher ADRs in 9-minute WT were also confirmed by the per-protocol (PP) analysis and subgroup analyses, with an increased rate of sessile serrated lesion detection in the 9-minute WT by PP analysis (4.0% vs. 1.3%, P = .04). Multivariate logistic regression demonstrated that the 9-minute WT was independently associated with increased ADR (P = .005). CONCLUSIONS: Prolonging WT from 6 to 9 minutes significantly improved ADR, especially in the proximal colon and for less experienced colonoscopists. A 9-minute WT benchmark should be considered as one of the quality indicators of colonoscopy. ClinicalTrials.gov (identifier, NCT03399045).

Magnetically Controlled Capsule Endoscopy for Assessment of Antiplatelet Therapy-Induced Gastrointestinal Injury.

BACKGROUND: Gastrointestinal bleeding is the most frequent major complication of antiplatelet therapy. In patients at low bleeding risk, however, clinically overt gastrointestinal bleeding is relatively uncommon. OBJECTIVES: The authors sought to assess the effects of different antiplatelet regimens on gastrointestinal mucosal injury by means of a novel magnetically controlled capsule endoscopy system in patients at low bleeding risk. METHODS: Patients (n = 505) undergoing percutaneous coronary intervention in whom capsule endoscopy demonstrated no ulcerations or bleeding (although erosions were permitted) after 6 months of dual antiplatelet therapy (DAPT) were randomly assigned to aspirin plus placebo (n = 168), clopidogrel plus placebo (n = 169), or aspirin plus clopidogrel (n = 168) for an additional 6 months. The primary endpoint was the incidence of gastrointestinal mucosal injury (erosions, ulceration, or bleeding) at 6-month or 12-month capsule endoscopy. RESULTS: Gastrointestinal mucosal injury through 12 months was less with single antiplatelet therapy (SAPT) than with DAPT (94.3% vs 99.2%; P = 0.02). Aspirin and clopidogrel monotherapy had similar effects. Among 68 patients without any gastrointestinal injury at randomization (including no erosions), SAPT compared with DAPT caused less gastrointestinal injury (68.1% vs 95.2%; P = 0.006), including fewer new ulcers (8.5% vs 38.1%; P = 0.009). Clinical gastrointestinal bleeding from 6 to 12 months was less with SAPT than with DAPT (0.6% vs 5.4%; P = 0.001). CONCLUSIONS: Despite being at low risk of bleeding, nearly all patients receiving antiplatelet therapy developed gastrointestinal injury, although overt bleeding was infrequent. DAPT for 6 months followed by SAPT with aspirin or clopidogrel from 6 to 12 months resulted in less gastrointestinal mucosal injury and clinical bleeding compared with DAPT through 12 months. (OPT-PEACE [Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by Ankon Magnetically Controlled Capsule Endoscopy]; NCT03198741).

Glucagon-like peptide (GLP) -2 improved colonizing bacteria and reduced severity of ulcerative colitis by enhancing the diversity and abundance of intestinal mucosa.

The global incidence of ulcerative colitis (UC) continues to increase while it's clinical cure rate remains low. Intestinal mucosal ulcers have segmental distribution and variable severity. Intestinal bacteria are closely related to intestinal immunity and metabolism; however, the relationship between intestinal microbiome profile and the occurrence of UC, as well as the contribution of glucose metabolism, are not well understood. This was investigated in the present study using mucosal biopsies from patients with UC and healthy control subjects. We performed high throughput 16S rRNA gene sequencing to estimate microbiota composition and abundance as well as their association with clinical indices such as lesion severity. The results showed that the diversity and abundance of intestinal microbiota were significantly lower in patients with UC than in healthy subjects; however, these were unrelated to ulcer severity. Serum glucagon-like peptide 2 (GLP-2) level was associated with reduced microbiota diversity and abundance in UC. These results indicate that colonization by specific microbiota is not the main determinant of pathologic status in UC. Additionally, therapeutic strategies that increase GLP-2 levels in intestinal mucosa may be effective in the treatment of UC.

Comparison of Water Immersion Versus Air Insufflation Colonoscopy Under Various Bowel Preparation Conditions.

BACKGROUND: To investigate the differences between water immersion (WI) and air insufflation (AI) for colonoscopy under various bowel preparation conditions. METHODS: In this study, 526 outpatients were randomly assigned to two groups, namely a WI group (n = 263) and an AI group (n = 263). During the procedure, the quality of bowel preparation, abdominal pain score, cecal intubation rate (CIR), adenoma detection rate (ADR), the intubation times, and other indicators were recorded. After reaching the cecum, each group of patients was subdivided into one of four grades (excellent, good, fair, and poor) according to the quality of bowel preparation. RESULTS: Under various bowel preparation conditions, the pain scores of the AI group were higher than those of the WI group (P < .05), but there was no significant difference between the two groups in CIR (P > .05). For the WI group compared with the AI group, the cecal intubation time (CIT) was prolonged under good bowel preparation (P = .045) and fair bowel preparation (P < .001). No significant differences were observed between the two groups on ADR in all patients (P = .476). CONCLUSION: Compared with AI colonoscopy, WI colonoscopy can decrease colonoscopy-related pain in patients for unsedated colonoscopy under various bowel preparation conditions, but there is no significant difference in CIR. WI colonoscopy requires longer CIT in patients with good and fair bowel preparation conditions. WI colonoscopy does not significantly increase ADR.

Transfer of dechlorane plus between human breast milk and adipose tissue and comparison with legacy lipophilic compounds.

In this study, levels of dechlorane plus (DP) in breast milk and matched adipose tissue samples were measured from 54 women living in Wenling, China. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured simultaneously for comparison. The levels of ∑DPs/∑PBDEs varied from less than one to several dozens of ng g-1 lipid weight (lw) in matrices and the levels of ∑PCBs varied between several to hundreds of ng g-1 lw. In the same matrix, ∑DPs and ∑PCBs/∑PBDEs showed a significant relationship (p < 0.05), indicating that they shared common sources. Accordingly, there was a strong association of lipid-adjusted concentrations of individual compounds (BDE-209 excluded) between matrices (p < 0.001), suggesting that breast milk could be a proxy for adipose tissue in human bioburden monitoring of these compounds. The predicted lipid-adjusted milk/adipose ratios varied from 0.62 to 1.5 but showed significant differences (p<0.001) between compounds, suggesting a compound-specific transfer between milk lipids and adipose tissue lipids. Specifically, the milk/adipose ratios for syn-DP and anti-DP (-1.40 and 1.3, respectively) were significantly higher than those of CB congeners and hexa/hepta-BDE congeners (p < 0.05). In addition, unlike PCBs/PBDEs (excluding BDE-209), DP's hydrophobicity might not be responsible for its preferable distribution in milk lipids. Instead, the interaction with nonlipid factors played a key role. The fraction of anti-DP between the two kinds of matrices was not significantly different, suggesting that the biochemical transfer processes may not be efficient enough to distinguish DP isomers. Nevertheless, the congener patterns of PCBs/PBDEs gave a clue about the compound-specific transfer between milk and adipose tissue. To our knowledge, this is the first to report the relationships of DP between adipose tissue and breast milk. These results could provide useful and in-depth information on biomonitoring of DP and facilitate the understanding of the accumulation and excretion potentials of DP and its distribution-related mechanism in humans.

Bioaccumulation and transfer characteristics of dechlorane plus in human adipose tissue and blood stream and the underlying mechanisms.

In this study, bioaccumulation and transfer characteristics of dechlorane plus (DP) were examined between human adipose tissue and matched maternal serum, and the possible transfer mechanism between tissues was further discussed. The median level of total DP was 971 pg g-1 wet weight (ww) and 1.22 ng g-1 lipid weight (lw) in adipose tissue, respectively, and was 34.7 pg g-1 ww and 3.98 ng g-1 lw for serum, respectively. DP wet levels' positive association with fat contents of five types of human tissues indicated that DP distribution might be related to lipid-driven mechanism. However, the lipid-adjusted adipose-serum partitioning ratios were estimated to be 0.35 for syn-DP and 0.35 for anti-DP, accordingly, which implied that the DP distribution between serum and adipose tissues, was not only regulated by the tissue lipid contents. Both the internal mono-dechlorination of anti-DP, and stereo-selective behavior of DP isomers were not found in DP transfer from blood to adipose tissue. The marginal positive relationship was observed between serum levels and apolipoprotein A concentrations (p = 0.095 for total DP and 0.045 for syn-DP), and neither association was found between serum levels and thyroid hormone concentrations (THs). To our best knowledge, this is the first report about the accumulation relationship of DP between human adipose tissue and blood stream with the corresponding distribution-related mechanism.

Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions.

BACKGROUND AND AIM: Linaclotide is a guanylate cyclase-C agonist approved in multiple countries to treat irritable bowel syndrome with constipation (IBS-C). China has unmet need for well-tolerated therapy that is effective in treating both bowel and abdominal symptoms of IBS-C. This trial evaluated linaclotide's efficacy and safety in IBS-C patients in China and other regions. METHODS: This Phase 3, double-blind trial randomized IBS-C patients to once-daily oral 290-µg linaclotide or placebo at centers in China, North America, and Oceania. Patients reported bowel and abdominal symptoms daily; adverse events were monitored. Co-primary and secondary endpoints were tested using a predefined three-step serial gatekeeping multiple comparisons procedure. RESULTS: The intent-to-treat population included 839 patients (mean age = 41 years; 82% female; 81% Asian). The trial met all co-primary and secondary endpoints. Co-primary responder criteria were met by 60.0% of linaclotide patients versus 48.8% of placebo patients for abdominal pain/discomfort (≥ 30% decrease for ≥ 6/12 weeks; P < 0.05), and 31.7% of linaclotide versus 15.4% of placebo patients for IBS degree of relief (score ≤ 2 for ≥ 6/12 weeks; P < 0.0001). Secondary 12-week change-from-baseline endpoints (spontaneous bowel movement/complete spontaneous bowel movement frequency, stool consistency, straining, abdominal pain, abdominal discomfort, and abdominal bloating) were significantly improved with linaclotide versus placebo (all P < 0.0001). Diarrhea was the most common adverse event (9.4% linaclotide, 1.2% placebo). Discontinuation rates due to diarrhea were low (0.7% linaclotide, 0.2% placebo). CONCLUSIONS: Once-daily 290-µg linaclotide improved bowel habits, abdominal symptoms, and global measures in a predominantly Chinese IBS-C population.

Partitioning of polybrominated biphenyl ethers from mother to fetus and potential health-related implications.

Presently, knowledge on the partitioning of polybrominated biphenyl ethers (PBDEs) from mother to fetus and the relationship between PBDE exposure and the levels of thyroid hormones (THs) needs to be extended further. In the present study, we investigated the concentrations of PBDEs in paired mother-fetus samples from 72 pregnant women in Wenling, China. The detection of PBDE concentration suggested that the expectant women living in Wenling for over 20 years might be highly exposed to PBDEs, which is largely ascribed to e-waste recycling activities in the local environment. The median concentration ratios between paired cord serum and maternal serum for higher-brominated BDEs were smaller than those for lower-brominated BDEs (p < 0.05). This result indicated that the placenta could hinder the transfer of PBDEs from mother to fetus, and the hindrance effect increased with higher-brominated congeners. Median ratios of paired placenta vs. maternal serum concentrations varied in a narrow range (0.15-0.25), with significantly lower value for BDE-209 than that for BDE-28 (p < 0.01). The extent of transplacental transfer was larger than that of placental retention for eight BDE congeners (p < 0.01). The concentration of BDE congeners among the paired samples could be fitted by equations, implying that their distribution could be predicted for each other (p < 0.001). There was a significant association between BDE-153 and TT4 levels in maternal serum from Wenling local residents (p < 0.05), suggesting potential implications for fetal development and their mothers' health in e-waste recycling environment. In addition, it was found that the relationship between BDEs and TH levels was likely affected by the exposure duration of the population to PBDEs.

EphB6 overexpression and Apc mutation together promote colorectal cancer.

The erythropoietin-producing hepatocyte (Eph) family tyrosine kinases play important roles in tumorigenesis and cancer aggression. In this study, we investigated the role of EphB6 in oncogenic transformation of colorectal epithelial cells in vitro and in vivo. EphB6 is upregulated in human colorectal cancer (CRC) tissues as compared to normal tissues, and its overexpression promotes proliferation, migration and invasion by IMCE colorectal adenoma cells, in which one Apc allele is mutated. EphB6 overexpression together with Apc mutation leads to the development of colorectal tumors in vivo. Expression microarrays using mRNAs and lncRNAs isolated from EphB6-overexpresssing IMCE and control cells revealed a large number of dysregulated genes involved in cancer-related functions and pathways. The present study is the first to demonstrate that EphB6 overexpression together with Apc gene mutations may enhance proliferation, invasion and metastasis by colorectal epithelial cells. Microarray data and pathway analysis of differentially expressed genes provided insight into possible EphB6-regulated mechanisms promoting tumorigenesis and cancer progression. EphB6 overexpression may represent a novel, effective biomarker predictive of cell proliferation, invasion and metastasis patterns in CRC tumors.

Colorectal cancer risk genes are functionally enriched in regulatory pathways.

Colorectal cancer (CRC) is a common complex disease caused by the combination of genetic variants and environmental factors. Genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. However, the potential genetic mechanisms for newly identified CRC susceptibility variants are still unclear. Here, we selected 85 CRC susceptibility variants with suggestive association P < 1.00E-05 from the National Human Genome Research Institute GWAS catalog. To investigate the underlying genetic pathways where these newly identified CRC susceptibility genes are significantly enriched, we conducted a functional annotation. Using two kinds of SNP to gene mapping methods including the nearest upstream and downstream gene method and the ProxyGeneLD, we got 128 unique CRC susceptibility genes. We then conducted a pathway analysis in GO database using the corresponding 128 genes. We identified 44 GO categories, 17 of which are regulatory pathways. We believe that our results may provide further insight into the underlying genetic mechanisms for these newly identified CRC susceptibility variants.

Arsenic trioxide induces apoptosis of human gastrointestinal cancer cells.

AIM: To investigate the changes in apoptosis in gastrointestinal cancer cells from patients with gastrointestinal cancers treated with arsenic trioxide (As2O3); and to study the possible molecular mechanisms of such changes by detecting the expression levels of p53 and Bcl-2. METHODS: Twenty patients with gastrointestinal adenocarcinoma based on endoscopic and biopsy findings (ten patients with gastric cancer and ten patients with colorectal cancer) who received treatment in our hospital between August 2007 and December 2008 were included in this study. None of the patients had received anti-tumour agents prior to As2O3 treatment. As2O3 was administered intravenously at a dose of 0.01 g/d diluted with 5% glucose in normal saline for 2-3 h for 3 consecutive days before surgery. Morphological changes associated with apoptosis of gastrointestinal cancer cells were observed by light microscopy. Changes in the apoptotic index induced by As2O3 were investigated using the terminal deoxynucleotidyl transferase dUTP nick end labelling method. Expression levels of p53 and Bcl-2 proteins in gastrointestinal cancer tissues were determined by immunohistochemistry. RESULTS: The apoptotic index of human gastrointestinal cancer cells was higher in cells from patients treated with As2O3 than in those not treated (P < 0.05). p53 protein expression in gastrointestinal tissues was unchanged by As2O3 (P > 0.05). However, Bcl-2 protein expression in gastrointestinal tissues was down-regulated by As2O3 (P < 0.01). CONCLUSION: These results demonstrate that As2O3 treatment in patients with gastrointestinal cancers can induce apoptosis in gastrointestinal cancer cells and down-regulate Bcl-2 protein expression.

Placental transfer of dechlorane plus in mother-infant pairs in an e-waste recycling area (Wenling, China).

It has been reported that breastfeeding can expose newborns to dechlorane plus (DP), but transplacental transfer of DP has not been documented. We measured DP and its dechlorinated analogs in matched maternal blood-placenta-cord blood samples from 72 residents of the e-waste recycling area of Wenling, China. DP was detected in cord sera, indicating the occurrence of prenatal DP exposure and the transfer of DP across the placenta. The concentration ratio in the cord serum and maternal serum was estimated to be 0.45 for syn-DP and 0.35 for anti-DP, indicating the placenta partially limited DP transfer with a greater extent for anti-DP. The DP concentrations in the maternal serum, placenta, and cord serum strongly correlated, indicating that DP could transfer between the tissues. The DP concentrations in the matched samples could be predicted from each other. The anti-DP/total DP concentration ratios in the placentas and cord sera were significantly different from those in the maternal sera, suggesting that DP stereoselectively bioaccumulates in human tissues. When the congener concentrations of polybrominated diphenyl ethers (PBDEs) were used as control variables, DP and total triiodothyronine concentrations were associated in the sera from mothers who had lived in Wenling for over 20 years.

[Ethmoid sinus foreign body long-term residence in one case].

Ethmoid sinus foreign body can be divided into endogenous and exogenous, the clinically referred mostly belonging to the exogenous foreign body. The exogenous ethmoid sinus foreign body generally has a history of facial trauma, its clinical manifestations are associated with the foreign body size, nature, residence time and location. Using X-ray, CT scan can further confirm the diagnosis. Removing the ethmoid sinus foreign body may have a better therapeutic effect by endoscopic sinus surgery. Here we report a rare case of foreign body in the ethmoid sinus.

Dechlorane Plus and its dechlorinated analogs from an e-waste recycling center in maternal serum and breast milk of women in Wenling, China.

We measured Dechlorane Plus (DP) and its dechlorinated analogs in the blood and milk from women living in e-waste recycling sites in Wenling of Taizhou region, China (n = 49). Both syn-DP and anti-DP were detected in all samples. Another compound, Cl(11)-DP, was detected in 45% and 84% of milk and serum samples, respectively. DP levels in blood and milk from residents living in the local environment >20 yrs (R(20) group) were significantly higher than those living in Taizhou <3 yrs (R(3) group) (p < 0.05). The milk/serum partition coefficient from the same women was approximately 0.43 and 0.47 for syn-DP and anti-DP, respectively. A similar value in milk compared with anti-DP/∑DPs (f(anti)) in serum suggested that stereoselective DP bio-accumulation did not occur during the DP transport from blood to milk. This result indicate that DP can bio-accumulate in blood and milk with the low milk/serum partition coefficient and similar blood and milk stereoselective bio-accumulation profiles.