Construction of a preoperative nomogram model for predicting perineural invasion in advanced gastric cancer.

Objective: This study aimed to develop and validate a clinical and imaging-based nomogram for preoperatively predicting perineural invasion (PNI) in advanced gastric cancer. Methods: A retrospective cohort of 351 patients with advanced gastric cancer who underwent surgical resection was included. Multivariable logistic regression analysis was conducted to identify independent risk factors for PNI and to construct the nomogram. The performance of the nomogram was assessed using calibration curves, the concordance index (C-index), the area under the curve (AUC), and decision curve analysis (DCA). The disparity in disease-free survival (DFS) between the nomogram-predicted PNI-positive group and the nomogram-predicted PNI-negative group was evaluated using the Log-Rank test and Kaplan-Meier analysis. Results: Extramural vascular invasion (EMVI), Borrmann classification, tumor thickness, and the systemic inflammation response index (SIRI) emerged as independent risk factors for PNI. The nomogram model demonstrated a commendable AUC value of 0.838. Calibration curves exhibited excellent concordance, with a C-index of 0.814. DCA indicated that the model provided good clinical net benefit. The DFS of the nomogram-predicted PNI-positive group was significantly lower than that of the nomogram-predicted PNI-negative group (p < 0.001). Conclusion: This study successfully developed a preoperative nomogram model that not only effectively predicted PNI in gastric cancer but also facilitated postoperative risk stratification.

Structured Reporting of Computed Tomography Enterography in Crohn's Disease.

BACKGROUND: To compare the integrity, clarity, conciseness, etc., of the structured report (SR) versus free-text report (FTR) for computed tomography enterography of Crohn's disease (CD). METHODS: FTRs and SRs were generated for 30 patients with CD. The integrity, clarity, conciseness etc., of SRs versus FTRs, were compared. In this study, an evidence-based medicine practice model was utilized on 92 CD patients based on SR in order to evaluate its clinical value. Then, the life quality of the patients in two groups was evaluated before and after three months of intervention using an Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: SRs received higher ratings for satisfaction with integrity (median rating 4.27 vs. 3.75, P=0.008), clarity (median rating 4.20 vs. 3.43, P=0.003), conciseness (median rating 4.23 vs. 3.20, P=0.003), the possibility of contacting a radiologist to interpret (median rating 4.17 vs. 3.20, P<0.001), and overall clinical impact (median rating 4.23 vs. 3.27, P<0.001) than FTRs. Besides, research group had higher score of IBDQ intestinal symptom dimension (median score 61.13 vs. 58.02, P=0.003), IBDQ systemic symptom dimension (median score 24.48 vs. 20.67, P<0.001), IBDQ emotional capacity dimension (median score 65.65 vs. 61.74, P<0.001), IBDQ social ability dimension (median score 26.80 vs. 22.37, P<0.001), and total IBDQ score (median score 178.07 vs. 162.80, P<0.001) than control group. CONCLUSION: The SR of CTE in CD patients was conducive to improving the quality and readability of the report, and CD patients' life quality could significantly improve after the intervention of an evidence-based medicine model based on SR.

Hyperglycemia Aggravates the Cerebral Ischemia Injury via Protein O-GlcNAcylation.

BACKGROUND: At least one-third of Alzheimer's disease (AD) patients have cerebrovascular abnormalities, micro- and macro-infarctions, and ischemic white matter alterations. Stroke prognosis impacts AD development due to vascular disease. Hyperglycemia can readily produce vascular lesions and atherosclerosis, increasing the risk of cerebral ischemia. Our previous research has demonstrated that protein O-GlcNAcylation, a dynamic and reversible post-translational modification, provides protection against ischemic stroke. However, the role of O-GlcNAcylation in the exacerbation of cerebral ischemia injury due to hyperglycemia remains to be elucidated. OBJECTIVE: In this study, we explored the role and underlying mechanism of protein O-GlcNAcylation in the exacerbation of cerebral ischemia injury caused by hyperglycemia. METHODS: High glucose-cultured brain microvascular endothelial (bEnd3) cells were injured by oxygen-glucose deprivation. Cell viability was used as the assay result. Stroke outcomes and hemorrhagic transformation incidence were assessed in mice after middle cerebral artery occlusion under high glucose and streptozotocin-induced hyperglycemic conditions. Western blot estimated that O-GlcNAcylation influenced apoptosis levels in vitro and in vivo. RESULTS: In in vitro analyses showed that Thiamet-G induces upregulation of protein O-GlcNAcylation, which attenuates oxygen-glucose deprivation/R-induce injury in bEnd3 cells cultured under normal glucose conditions, while aggravated it under high glucose conditions. In in vivo analyses, Thiamet-G exacerbated cerebral ischemic injury and induced hemorrhagic transformation, accompanied by increased apoptosis. While blocking protein O-GlcNAcylation with 6-diazo-5-oxo-L-norleucine alleviated cerebral injury of ischemic stroke in different hyperglycemic mice. CONCLUSION: Overall, our study highlights the crucial role of O-GlcNAcylation in exacerbating cerebral ischemia injury under conditions of hyperglycemia. O-GlcNAcylation could potentially serve as a therapeutic target for ischemic stroke associated with AD.

A novel variant in NBAS identified from an infant with fever-triggered recurrent acute liver failure disrupts the function of the gene.

Mutations in the neuroblastoma amplified sequence (NBAS) gene correlate with infantile acute liver failure (ALF). Herein, we identified a novel NBAS mutation in a female infant diagnosed with recurrent ALF. Whole-exome and Sanger sequencing revealed that the proband carried a compound heterozygous mutation (c.938_939delGC and c.1342 T > C in NBAS). NBAS c.938_939delGC was presumed to encode a truncated protein without normal function, whereas NBAS c.1342 T > C encoded NBAS harboring the conserved Cys448 residue mutated to Arg448 (p.C448R). The proportion of CD4 + T cells decreased in the patient's peripheral CD45 + cells, whereas that of CD8 + T cells increased. Moreover, upon transfecting the same amount of DNA expression vector (ectopic expression) encoding wild-type NBAS and p.C448R NBAS, the group transfected with the p.C448R NBAS-expressing vector expressed less NBAS mRNA and protein. Furthermore, ectopic expression of the same amount of p.C448R NBAS protein as the wild-type resulted in more intracellular reactive oxygen species and the induction of apoptosis and expression of marker proteins correlating with endoplasmic reticulum stress in more cultured cells. This study indicated that p.C448R NBAS has a function different from that of wild-type NBAS and that the p.C448R NBAS mutation potentially affects T-cell function and correlates with ALF.

Comparison of Contrast-enhanced versus Non-enhanced Helical Computed Tomography in the Diagnosis of Acute Appendicitis: A Meta-analysis.

The aim of this review was to compare the performance of contrast-enhanced versus non-contrast-enhanced helical computed tomography (CT) for acute appendicitis as reported. A systematic search of PubMed and Embase was conducted. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curves (AUC) were evaluated using Meta-DiSc. Quality was assessed using QUADAS 2. Eight articles with 1602 patients were included. For contrast-enhanced CT, the pooled sensitivity was 0.95 (95% CI: 0.93-0.96) with a specificity of 0.94 (95%CI: 0.93-0.96). The PLR, NLR, and DOR were 14.74 (95%CI: 9.06-23.97), 0.06 (95%CI: 0.03-0.11), and 305.31 (95%CI: 107.14-870.08), respectively. For non-contrast-enhanced CT, the pooled sensitivity was 0.85 (95% CI: 0.82-0.87) with a specificity of 0.93 (95%CI: 0.92-0.95). The PLR, NLR, and DOR were 12.22 (95% CI: 9.52-15.69), 0.15 (95%CI: 0.09-0.25), 80.98 (95%CI: 41.65-157.45), respectively. The AUC was not statistically different (Z=0.737, p=0.461). This data suggest that the contrast-enhanced CT has better diagnostic performance for acute appendicitis than non-contrast CT. Key Words: Acute appendicitis, Contrast-enhanced computed tomography' scan, Non-contrast-enhanced computed tomography' scan, Meta-analysis.

Role of clinical data and multidetector computed tomography findings in acute superior mesenteric artery embolism.

BACKGROUND: Superior mesenteric artery embolism (SMAE) has acute onset and fast progression, which seriously threatens the life of patients. Multidetector computed tomography (MDCT) is one of the most important diagnostic methods for SMAE, which plays an important role in the diagnosis and prognosis of SMAE. AIM: To evaluate the value of combined clinical data and MDCT findings in the diagnosis of acute SMAE and predict the risk factors for SMAE-related death. METHODS: Data from 53 SMAE patients who received abdominal MDCT multi-phase enhancement and superior mesenteric artery digital subtraction angiography examinations were collected. Univariate cox regression and multivariate cox model were used to analyze the correlation between death risk and clinical and computed tomography features in SMAE patients. RESULTS: Univariate Cox regression model showed that intestinal wall thinning, intestinal wall pneumatosis, blood lactate > 2.1 mmol/L and blood pH < 7.35 increased the risk of death in patients with SMAE. After adjusting for age, sex, embolic involvement length and embolic distribution region, multivariate Cox regression model I showed that blood lactate > 2.1 mmol/L (HR = 5.26, 95%CI: 1.04-26.69, P = 0.045) and intestinal wall thinning (HR = 9.40, 95%CI: 1.05-83.46, P = 0.044) were significantly increases the risk of death in patients with SMAE. CONCLUSION: For patients with SAME, increased blood lactate and intestinal wall thinning are the risk factors for death; hence, close monitoring may reduce the mortality rate. Clinical observation combined with MDCT signs can significantly improve SMAE diagnosis.

A study on spinal level, length, and branch type of the inferior mesenteric artery and the position relationship between the inferior mesenteric artery, left colic artery, and inferior mesenteric vein.

BACKGROUND: This study was aimed to explore the clinical application of dual-energy computed tomography (DECT) monoenergetic plus (mono+) imaging to evaluate anatomical variations in the inferior mesenteric artery (IMA). METHODS: The clinical and imaging data of 212 patients who had undergone total abdominal DECT were retrospectively analyzed. The post-processing mono+ technique was used to obtain 40-keV single-level images in the arterial phase. Three-dimensional reconstruction was performed to evaluate the relationship between the IMA root position and the spinal level, IMA length, and IMA branch type, as well as the position of the left colic artery (LCA) and inferior mesenteric vein (IMV) at the IMA root level. RESULTS: The IMA root was located at the L3 level in 78.3% of cases and at the L2/L3 level in 3.3%. The highest vertebral level of IMA origin was L2 (4.2%), and the lowest was L4 (7.1%). The distance from the IMA root to the level of the sacral promontory was 99.58 ± 13.07 mm, which increased with the elevation of the IMA root at the spinal level. Of the patients, 53.8% demonstrated Type I IMA, 23.1% Type II, 20.7% Type III, and 2.4% Type IV. The length of the IMA varied from 13.6 to 66.0 mm. 77.3% of the IMAs belonged to Type A, the adjacent type, and 22.7% to Type B, the distant type. CONCLUSION: DECT mono+ can preoperatively evaluate the anatomical characteristics of the IMA and the positional relationship between the LCA and IMV at the IMA root level, which would help clinicians plan individualized surgery for patients.

Efficiency of dual-energy computed tomography enterography in the diagnosis of Crohn's disease.

BACKGROUND: This retrospective study aimed to investigate the usefulness of the optimized kiloelectron volt (keV) for virtual monoenergetic imaging (VMI) combined with iodine map in dual-energy computed tomography enterography (DECTE) in the diagnosis of Crohn's disease (CD). METHODS: Seventy-two patients (mean age: 41.89 ± 17.28 years) with negative computed tomography enterography (CTE) were enrolled for investigating the optimized VMI keV in DECTE by comparing subjective and objective parameters of VMIs that were reconstructed from 40 to 90 keV. Moreover, 68 patients (38.27 ± 15.10 years; 35 normal and 33 CD) were included for evaluating the diagnostic efficacy of DECTE iodine map at the optimized VMI energy level and routine CTE for CD and active CD. Statistical analysis for all data was conducted. RESULTS: Objective and subjective imaging evaluations showed the best results at 60 keV for VMIs. The CT values of the normal group, active subgroup, and CD group during the small intestinal phase at routine 120 kVp or 60 keV VMI had significant differences. The diagnostic efficacy of an iodine map was the best when NIC = 4% or fat value = 45.8% for CD, whereas NIC < 0.35 or the fat value < 0.38 for active CD. The combined routine CTE and optimized VMI improved the diagnostic efficacy (P < 0.001). CONCLUSIONS: VMI at 60 keV provided the best imaging quality on DECTE. NIC and fat value provided important basis for active CD evaluation. Routine CTE combined with VMI at 60 keV improved the diagnostic efficiency for CD.

The prognosis prediction significance of Hounsfield unit value for stroke patients treated by intravenous thrombolysis.

BACKGROUND: Intravenous thrombolysis (IVT) is a rapid and effective treatment in the early stage of ischemic stroke patients and the purpose of this work is to explore the significance of Hounsfield unit (HU) value in Alberta Stroke Program Early CT Score (ASPECTS) for predicting the clinical prognosis of stroke patients with middle cerebral artery occlusion (MCAO) treated by IVT. METHODS: The 84 stroke patients with MCAO treated by IVT were divided into good prognosis group (48 cases) and poor prognosis group (36 cases). HU ratio and HU difference calculated from non-contrast computed tomography between groups were analyzed. RESULTS: The HU ratio of good prognosis group was higher than that in poor prognosis group and the HU difference of good prognosis group was lower than that in poor prognosis group (P < 0.05). The HU ratio and ASPECTS were negatively correlated with the infarct volume, and the HU difference was positively correlated with the infarct volume (P < 0.05). HU difference was an independent risk factor for prognosis of patients with MCAO treated by IVT. The area under the receiver operating characteristic curve of HU ratio and HU difference for prognosis was 0.743 and 0.833 respectively. CONCLUSION: The HU value changes are related to the clinical prognosis of stroke patients with MCAO treated by IVT, HU value may be a prognostic indicator for stroke patients with MCAO treated by IVT.

Protein O-GlcNAcylation alleviates small intestinal injury induced by ischemia-reperfusion and oxygen-glucose deprivation.

Protein O-GlcNAcylation is a dynamic post-translational protein modification that regulates fundamental cellular functions in both normal physiology and diseases. The levels of protein O-GlcNAcylation are determined by flux of the hexosamine biosynthetic pathway (HBP), which is a branch of glycolysis, and are directly controlled by a pair of enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). An increase in protein O-GlcNAcylation has been shown to have protective effects on ischemia-related insults in the heart and brain. To determine whether O-GlcNAcylation plays a beneficial role in ischemia-reperfusion (IR)-induced intestinal injury, we used pharmacological manipulation of O-GlcNAc to induce loss- and gain-of-function conditions and evaluated the viability and apoptosis of intestinal epithelioid cells in an in vitro oxygen-glucose deprivation (OGD) model and tissue injury grade in a small intestinal ischemia-reperfusion (SIIR) mouse model. We found that 1) Upregulation of O-GlcNAcylation induced by glucosamine (GlcN, increase in HBP flux) or thiamet G (an OGA inhibitor) enhanced intestinal cell survival in the OGD model. In contrast, downregulation of O-GlcNAcylation induced by DON (due to a reduction in HBP flux) or OMSI-1 (an OGT inhibitor) made the cells more susceptible to hypoxia injury. 2) Reducing the increase in O-GlcNAcylation levels with a combination of either GlcN with DON or thiamet G with OMSI-1 partly canceled its protective effect on OGD-induced cell injury. 3) In the in vivo SIIR mouse model, GlcN augmented intestinal protein O-GlcNAcylation and significantly alleviated intestinal injury by inhibiting cell apoptosis. These results indicate that acute increases in protein O-GlcNAcylation confer protection against intestinal ischemia insults, suggesting that O-GlcNAcylation, as an endogenous stress sensor, could be a universal protective mechanism and could be a potential therapeutic target for intestinal ischemic disease.

GPR126 regulates colorectal cancer cell proliferation by mediating HDAC2 and GLI2 expression.

The G-protein-coupled receptor 126 (GPR126) may play an important role in tumor development, although its role remains poorly understood. We found that GPR126 had higher expression in most colorectal cancer cell lines than in normal colon epithelial cell lines, and higher expression levels in colorectal cancer tissues than in normal adjacent colon tissues. GPR126 knockdown induced by shRNA inhibited cell viability and colony formation in HT-29, HCT116, and LoVo cells, decreased BrdU incorporation into newly synthesized proliferating HT-29 cells, led to an arrest of cell cycle progression at the G1 phase in HCT-116 and HT-29 cells, and suppressed tumorigenesis of HT-29, HCT116, and LoVo cells in nude mouse xenograft models. GPR126 knockdown engendered decreased transcription and translation of histone deacetylase 2 (HDAC2), previously implicated in the activation of GLI1 and GLI2 in the Hedgehog signaling pathway. Ectopic expression of HDAC2 in GPR126-silenced cells restored cell viability and proliferation, GLI2 luciferase reporter activity, partially recovered GLI2 expression, and reduced the cell cycle arrest. HDAC2 regulated GLI2 expression and, along with GLI2, it bound to the PTCH1 promoter, as evidenced by a chip assay with HT-29 cells. Purmorphamine, a hedgehog agonist, largely restored the cell viability and expression of GLI2 proteins in GPR126-silenced HT-29 cells, whereas GANT61, a hedgehog inhibitor, further enhanced the GPR126 knockdown-induced inhibitory effects. Our findings demonstrate that GPR126 regulates colorectal cancer cell proliferation by mediating the expression of HDAC2 and GLI2, therefore it may represent a suitable therapeutic target for colorectal cancer treatment.

Comparison of the Diagnostic Performance of PI-RADS V1 and PI-RADS V2 for the Detection of Prostate Cancer: A Meta-Analysis.

PURPOSE: In order to comprehensively determine the diagnostic accuracy of the Prostate Imaging Reporting and Data System version 1 (PI-RADS V1) and PI-RADS version 2 (PI-RADS V2) in prostate cancer (PCa) diagnosis. MATERIALS AND METHODS: The literatures were screened from the databases, including the Pubmed, Embase, Web of science and Cochrane Library up to January 20th, 2020. The meta-analysis was conducted by Meta-DiSc and quality assessment was performed by using the QUADAS. Furthermore, the sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), as well as receiver operating curve (ROC) related to diagnostic accuracy were pooled. RESULTS: A total of 6 articles containing 814 participants (379 patients) were included in the study. For PI-RADS V1, the combined sensitivity, specificity, PLR, NLR and DOR were 0.82 (95% CI: 0.77-0.85), 0.81 (95% CI: 0.77- 0.85), 4.58 (95% CI: 2.55-8.22), 0.24 (95% CI: 0.18-0.34) and 24.00 (95% CI: 10.38-55.51). With regard to PIRADS V2, the combined sensitivity, specificity, PLR, NLR and DOR were 0.88 (95% CI: 0.84-0.91), 0.81 (95% CI: 0.77-0.84), 4.34 (95% CI: 1.98-9.49), 0.16 (95% CI: 0.08-0.32) and 33.39 (95% CI: 15.05-74.05), respectively. Furthermore, except that the sensitivity of PI-RADS V2 was significantly greater than that of PI-RADS V1 (P = 0.027), there was no remarkably difference in other indicators for the diagnosis of PCa between the two versions. CONCLUSION: Both PI-RADS V1 and PI-RADS V2 showed good diagnostic performance for PCa diagnosis; moreover, there was no difference in the diagnostic effect between them.

Diagnostic significance of multidetector computed tomography (MDCT) in patients with small bowel obstruction: a meta-analysis.

PURPOSE: To assess the diagnostic value of multidetector computed tomography (MDCT) in small bowel obstruction (SBO) patients. METHODS: Relevant literature was searched from the Cochrane Library, Pubmed and Embase. The extracted effective data was calculated using the Meta-Disc 1.4 software; statistical heterogeneity was evaluated using Cochran's Q test and I2. RESULTS: A total of five articles were selected for the meta-analysis. In addition, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), as well as the diagnostic odds ratio (DOR) were 0.878 (95% CI 0.822-0.921), 0.807 (95% CI 0.753-0.854), 8.137 (95% CI 2.268-29.192), 0.127 (95% CI 0.040-0.4078) and 72.384 (95% CI 10.841-483.31), respectively. Furthermore, the AUC was 0.9648 with the Q of 0.9116. CONCLUSIONS: The data suggest that MDCT is an effective method for diagnosis of SBO.

The Potential Role of Protein Tyrosine Phosphatase, Receptor Type C (CD45) in the Intestinal Ischemia-Reperfusion Injury.

This study was designed to identify several key genes and their functions in preventing or ameliorating intestinal ischemia-reperfusion (IR) injury, which could provide rationale for further exploring the regulatory mechanisms or clinical treatment for intestinal IR injury. The microarray GSE37013 of human intestinal IR injury was downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) with changes of reperfusion time were screened using Short Time-series Expression Miner, followed by function enrichment analysis, protein-protein interaction (PPI) network, and module construction. Subsequently, the key DEGs were identified with VEEN analysis based on the significant results of function enrichment analysis and PPI module. Finally, the gene-drug interactions were predicted using DGIdb 2.0. The DEGs of intestinal IR injury were significantly divided into three clusters with changes of reperfusion time. The genes in the three clusters were mainly enriched in transmembrane transport, defense responses, and cellular component assembly related pathways, respectively. There were 121 nodes and 281 interactions in PPI network, including one significant submodule. Protein tyrosine phosphatase, receptor type C (PTPRC) was a hub code both in PPI network and in submodule. A total of eight key DEGs were identified but only PTPRC was predicted to be interacted with eight drugs, such as infliximab. Totally, eight key genes associated with intestinal IR were identified; PTPRC especially was the most prominent potential drug target. These findings provided several potential therapeutic targets or potential breakthrough area in the study of intestinal IR injury.