Development and validation of a novel scoring system based on a nomogram for predicting inadequate bowel preparation.

BACKGROUND AND AIMS: Adequate bowel preparation (BP) is crucial for the diagnosis of colorectal diseases. Identifying patients at risk of inadequate BP allows for targeted interventions and improved outcomes. We aimed to develop a model for predicting inadequate BP based on preparation-related factors. METHODS: Adult outpatients scheduled for colonoscopy between May 2022 and October 2022 were enrolled. One set (N = 913) was used to develop and internally validate the predictive model. The primary predictive model was displayed as a nomogram and then modified into a novel scoring system, which was externally validated in an independent set (N = 177). Inadequate BP was defined as a Boston Bowel Preparedness Scale (BBPS) score of less than 2 for any colonic segment. The model was evaluated by the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). RESULTS: Independent factors included in the prediction model were stool frequency ≤ 5 (15 points), preparation-to-colonoscopy interval ≥ 5 h (15 points), incomplete dosage (100 points), non-split dose (90 points), unrestricted diet (88 points), no additional water intake (15 points), and last stool appearance as an opaque liquid (0-80 points). The training set exhibited the following performance metrics for identifying BP failure: area under the curve (AUC) of 0.818, accuracy (ACC) of 0.818, positive likelihood ratio (PLR) of 2.397, negative likelihood ratio (NLR) of 0.162, positive predictive value (PPV) of 0.850, and negative predictive value (NPV) of 0.723. In the internal validation set, these metrics were 0.747, 0.776, 2.099, 0.278, 0.866, and 0.538, respectively. The external validation set showed values of 0.728, 0.757, 2.10, 0.247, 0.782, and 0.704, respectively, indicating strong discriminative ability. Calibration curves demonstrated close agreement, and DCA indicated superior clinical benefits at a threshold probability of 0.73 in the training cohort and 0.75 in the validation cohort for this model. CONCLUSIONS: This novel scoring system was developed from a prospective study and externally validated in an independent set based on 7 easily accessible variables, demonstrating robust performance in predicting inadequate BP.

Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease.

Foot-and-mouth disease (FMD) has caused severe economic losses to millions of farmers worldwide. In this work, the coding genes of 141-160 epitope peptide (EP141-160) of VP1 were inserted into the coat protein (CP) genes of MS2 in prokaryotic expression vector, and the recombinant protein self-assembled into virus-like particles (VLP). Results showed that the CP-EP141-160 VLP had a strong immunoreaction with the FMD virus (FMDV) antigen in vitro, and also had an effective immune response in mice. Further virus challenge tests were carried out on guinea pigs and swine, high-titer neutralizing antibodies were produced and the CP-EP141-160 VLP vaccine could protect most of the animals against FMDV.

Isocoumarins from American cockroach (Periplaneta americana) and their cytotoxic activities.

Four new isocoumarins (1-4), along with three known ones (5-7), were isolated from the 70% ethanol extract of the whole body of the traditional Chinese insect medicine, American cockroach (Periplaneta americana). The structures with absolute configurations of new compounds were elucidated by extensive spectroscopic methods in combination with X-ray diffraction experiment and CD analyses. Compounds 3-5 showed significant cytotoxic activities in HepG2 and MCF-7 cells with IC50 values in the ranges 6.41-23.91 µM and 6.67-39.07 µM, respectively.

The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal.

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be investigated. In the present study, we generated two truncated AIFs, AIFDelta1-480-FLAG, which is a FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360-480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to demonstrate that both the truncated proteins are expressed and located in the cytoplasm of transfected cells. AIFDelta1-480 but not AIF360-480 induces apoptosis in transfected cells. We also found that the expression of AIFDelta1-480 could initiate the release of cytochrome c from the mitochondria. The suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFDelta1-480. Therefore, AIFDelta1-480 is sufficient for inducing caspase-9-dependent apoptotic signaling, probably by promoting the release of cytochrome c. At last, we generated a chimeric immuno-AIFDelta1-480 protein, which comprised an HER2 antibody, a Pseudomonas exotoxin A translocation domain and AIFDelta1-480. Human Jurkat cells transfected with the immuno-AIFDeltal-480 gene could express and secrete the chimeric protein, which selectively recognize and kill HER2-overexpressing tumor cells. Our study demonstrates the feasibility of the immuno-AIFDeltal-480 gene as a novel approach to treating HER2-overexpressing cancers.

The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be investigated. In the present study, we generated two truncated AIFs, AIFΔ1-480-FLAG, which is a FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360-480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to demonstrate that both the truncated proteins are expressed and located in the cytoplasm of transfected cells. AIFΔ1-480 but not AIF360-480 induces apoptosis in transfected cells. We also found that the expression of AIFΔ1-480 could initiate the release of cytochrome c from the mitochondria. The suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFΔ1-480. Therefore, AIFΔ 1-480 is sufficient for inducing caspase-9-dependent apoptotic signaling, probably by promoting the release of cytochrome c. At last, we generated a chimeric immuno-AIFΔ 1-480 protein, which comprised an HER2 antibody, a Pseudomonas exotoxin A translocation domain and AIFΔ 1-480. Human Jurkat cells transfected with the immuno-AIFΔl-480 gene could express and secrete the chimeric protein, which selectively recognize and kill HER2-overexpressing tumor cells. Our study demonstrates the feasibility of the immuno-AIFΔl-480 gene as a novel approach to treating HER2-overexpressing cancers.