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ObjectivesTo mitigate the incidence of misdiagnosis and distinguish between gastric fundic tumors (GFTs) and thickened diaphragmatic crura (TDC).Materials and methodsComputed tomographic enterography (CTE) data from 3844 cases and computed tomographic gastrography (CTG) data from 4351 cases were retrospectively analyzed. A total of 105 cases were selected and categorized into three groups: 47 cases with TDC examined via CTE, 31 with adenocarcinoma, and 27 with gastrointestinal stromal tumors (GIST) examined via CTG. Inter-group differences in age, sex distribution, mass dimensions, mass-stomach interface (MSI), chief complaints, gastric underlying diseases, and enhancement patterns were analyzed.ResultsThe misdiagnosis rate of TDC as a tumor by radiologists is approximately 1.2% (47/3844). Age (p

Introduction: Tumor-associated calcium signal transducer 2 (Trop2) has been used as a transport gate for cytotoxic agents into cells in antibody–drug conjugate designs because of its expression in a wide range of solid tumors. However, the specific role of Trop2 itself in breast cancer progression remains unclear and small molecules targeting Trop2 have not yet been reported. Objectives: To screen small molecules targeting Trop2, and to reveal its pharmacological effects and the molecular mechanisms of action. Methods: Small molecule targeting Trop2 was identified by cell membrane chromatography, and validated by cellular thermal shift assay and point mutation analyses. We investigated the pharmacological effects of Trop2 inhibitor using RNA-seq, human foreskin fibroblast (HFF)-derived extracellular matrix (ECM), Matrigel drop invasion assays, colony-forming assay, xenograft tumor model, 4T1 orthotopic metastasis model and 4T1 experimental metastasis model. The molecular mechanism was determined using immunoprecipitation, mass spectrometry, immunofluorescence, immunohistochemistry and Western blotting. Results: Here we identified Bruceine D (BD) as the inhibitor of Trop2, and demonstrated anti-metastasis effects of BD in breast cancer. Notably, Lys307 and Glu310 residues of Trop2 acted as critical sites for BD binding. Mechanistically, BD suppressed Trop2-induced cancer metastasis by blocking the formation of Trop2/β-catenin positive loop, in which the Trop2/β-catenin complex prevented β-catenin from being degraded via the ubiquitin-proteosome pathway. Destabilized β-catenin caused by BD reduced nucleus translocation, leading to the reduction of transcription of Trop2, the reversal of epithelial-mesenchymal transition (EMT) process, and the inhibition of ECM remodeling, further inhibiting cancer metastasis. Additionally, the inhibitory effects of BD on lung metastatic colonization and the beneficial effects of BD on prolongation of survival were validated in 4T1 experimental metastasis model. Conclusions: These results support the tumor-promoting role of Trop2 in breast cancer by stabilizing β-catenin in Trop2/β-catenin positive loop, and suggest Bruceine D as a promising candidate for Trop2 inhibition.

CDC42 controls intestinal epithelial (IEC) stem cell (IESC) division. How aberrant CDC42 initiates intestinal inflammation or neoplasia is unclear. We utilized models of inflammatory bowel diseases (IBD), colorectal cancer, aging, and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and neoplasia. Intestinal specimens were collected to determine the levels of CDC42 in IBD or colorectal cancer. Cdc42 floxed mice were crossed with Villin-Cre, Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2, or Bmi1-CreERT2 mice to generate Cdc42 deficient mice. Irradiation, colitis, aging, and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation, IESC/progenitor regenerative capacity, and IEC repair. Our studies revealed that increased CDC42 in colorectal cancer correlated with lower survival; in contrast, lower levels of CDC42 were found in the inflamed IBD colon. Colonic Cdc42 depletion significantly reduced Lgr5+ IESCs, increased progenitors' hyperplasia, and induced mucosal inflammation, which led to crypt dysplasia. Colonic Cdc42 depletion markedly enhanced irradiation- or chemical-induced colitis. Depletion or inhibition of Cdc42 reduced colonic Lgr5+ IESC regeneration. In conclusion, depletion of Cdc42 reduces the IESC regeneration and IEC repair, leading to prolonged mucosal inflammation. Constitutive monogenic loss of Cdc42 induces mucosal inflammation, which could result in intestinal neoplasia in the context of aging.

Infrared small-target detection is now commonly used in maritime surveillance, flight guidance, and other fields. However, extracting small targets from complex backgrounds remains a challenging task due to the small-target scale and complex imaging environment. Many studies are based on designing model structures to enhance the precision of target detection, and the number of Params and FLOPs has been significantly augmented. In this work, a knowledge distillation-based detection method (KDD) is proposed to overcome this challenge. KDD employs the small-target labeling information provided by a large-scale teacher model to refine the training process of students, thereby improving the performance and becoming lightweight. Specifically, we added efficient local attention (ELA), which can accurately identify areas of interest while avoiding dimensionality reduction. In addition, we also added the group aggregation bridge (GAB) module to connect low-level and high-level features for the fusion of different feature scales. Furthermore, a feature fusion loss was introduced to enhance the precision of target detection. Extensive evaluations have demonstrated that KDD performs better compared to several methods, achieving extremely low Params and FLOPs, as well as higher FPS.

Abstract Background The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will be over the long term. As a result, we looked at the efficacy, safety, and consequences of adding COX-2 inhibitors to the treatment plan afterward. Methods In patients with advanced colorectal cancer, we compared the efficacy of celecoxib at two different doses (200 mg twice day and 400 mg twice daily) with placebo. To evaluate the impacts of post-treatment, several datasets from inception to June 2022 were searched. Response rate, illness control rate, and 3-year survival were the main results. And evaluated several safety outcomes, particularly those that were susceptible to adverse events. Results The study comprised a total of 9 randomized controlled trials (3206 participants). Celecoxib and rofecoxib doidn’t significantly improved the 1–3 year remission rate (OR, 1.57 [95% CI: 0.95–2.57]) and disease control rate (OR, 1.08 [95% CI: 0.99–1.17]). Subgroup analysis of different doses showed that 400 mg of celecoxib significantly improved the response rate (OR, 2.82 [95%CI: 1.20–6.61]). 200 mg celecoxib was not significant (OR, 1.28 [95% CI: 0.66–2.49]). Rofecoxib also did not fully improve disease response rates. Celecoxib at any dose improved 3-year survival (OR, 1.21 [95% CI: 1.02–1.45]). It is important to note that COX-2 inhibitors did not significantly enhance the likelihood of adverse events including gastrointestinal or cardiovascular side effects at any dose. Conclusions For patients with advanced colorectal cancer, a reasonable chemoprevention regimen can include celecoxib 400 mg twice daily.

Summary: Background: Voiding cystourethrography (VCUG) is the gold standard for the diagnosis and grading of vesicoureteral reflux (VUR). However, VUR grading from voiding cystourethrograms is highly subjective with low reliability. This study aimed to develop a deep learning model to improve reliability for VUR grading on VCUG and compare its performance to that of clinicians. Methods: In this retrospective study in China, VCUG images were collected between January 2019 and September 2022 from our institution as an internal dataset for training and 4 external data sets as external testing set for validation. Samples were divided into training (N = 1000) and validation sets (N = 500), internal testing set (N = 168), and external testing set (N = 280). An ensemble learning-based model, Deep-VCUG, using Res-Net 101 and the voting methods was developed to predict VUR grade. The grading performance was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and F1 score in the internal and external testing set. The performances of four clinicians (2 pediatric urologists and 2 radiologists) with and without the Deep-VCUG assisted to predict VUR grade were explored in external testing sets. Findings: A total of 1948 VCUG images were collected (Internal dataset = 1668; multi-center external dataset = 280). For assessing unilateral VUR grading, the Deep-VCUG achieved AUCs of 0.962 (95% confidence interval [CI]: 0.943–0.978) and 0.944 (95% [CI]: 0.921–0.964) in the internal and external testing sets, respectively, for bilateral VUR grading, the Deep-VCUG also achieved high AUCs of 0.960 (95% [CI]: 0.922–0.983) and 0.924 (95% [CI]: 0.887–0.957). The Deep-VCUG model using voting method outperformed single model and clinician in terms of classification based on VCUG image. Moreover, Under the Dee-VCUG assisted, the classification ability of junior and senior clinicians was significantly improved. Interpretation: The Deep-VCUG model is a generalizable, objective, and accurate tool for vesicoureteral reflux grading based on VCUG imaging and had good assistance with clinicians to VUR grading applicability. Funding: This study was supported by Natural Science Foundation of China, “Fuqing Scholar” Student Scientific Research Program of Shanghai Medical College, Fudan University, and the Program of Greater Bay Area Institute of Precision Medicine (Guangzhou).

Objective This study aimed to investigate the clinical significance of serum S100 calcium-binding protein A12 (S100A12) concentrations in patients with community-acquired pneumonia (CAP). Methods This was a case–control study. We selected 120 patients with CAP treated in Xichang People’s Hospital from January to June 2022 as the case group. Sixty healthy adults without a history of basic diseases were selected as the control group. The patients in the case group were divided into the low S100A12 and high S100A12 subgroups. Serum S100A12, C-reactive protein (CRP), and procalcitonin (PCT) concentrations, the leukocyte count, and other study parameters were compared. Results Serum S100A12, CRP, and PCT concentrations and the leukocyte count were higher in the case group than in the control group. The baseline confusion, urea, respiratory rate, blood pressure, and age ≥ 65 score, baseline pneumonia severity index score, and 30-day mortality rate were higher in the high S100A12 subgroup than in the low S100A12 subgroup. Serum CRP and PCT concentrations and the leukocyte count were higher in the high S100A12 subgroup than in the low S100A12 subgroup. Conclusion Patients with high serum S100A12 concentrations have more severe CAP, a more serious inflammatory reaction, and higher 30-day mortality.

Abstract Background Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion has been previously associated with developmental delay, mental retardation, epilepsy, autism, schizophrenia and congenital heart defects. The literature on this microdeletion is extensive and confusing, which is a challenge for genetic counselling. Case presentation We have performed prenatal diagnosis and genetic counseling of a paternally inherited 15q11.2 microdeletion. In this family, father with normal phenotype and fetus with abnormal phenotype have the same microdeletion. Conclusion Chromosomal microdeletions and microduplications are difficult to detect by conventional cytogenetics, combination of prenatal ultrasound, karyotype analysis, CMA and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

Abstract Background Epilepsy is one of the most common chronic neurological diseases that adversely impact the quality of life of patients and their families. The “Quality of Life of Childhood Epilepsy Questionnaire” (hereinafter referred to as “QOLCE-16”) is a 16-item measure that was designed to assess health-related quality of life (HRQOL) among children with epilepsy. The purpose of the study was to translate and evaluate the psychometric properties of the QOLCE-16. Methods The 10 steps of Principles of Good Practices for translation and cultural adaptation of measures were adopted to translate the QOLCE-16 into Chinese. After that, item analysis, floor effect and ceiling effect, internal consistency, test–retest reliabilities, content validity and construct validity were conducted to test its applicability in children with epilepsy in China. A total of 435 native Chinese-speaking parents with children who had epilepsy from one children’s hospital were invited to take part in the study, including a cognitive interview sample of 5 and a validation sample of 430. Results A total of 414 objects were enrolled in our study for psychometric testing. The results of the item analysis revealed QOLCE-16-C to have good discrimination, the floor effect and ceiling effect were 0.2% and 1.0% respectively, and each item was significantly related to the total scale (P

Abstract Background The role of sexually transmitted infections (STIs) in semen parameters and male infertility is still a controversial area. Previous studies have found bacterial infection in a minority of infertile leukocytospermic males. This study aims to investigate the prevalence of STIs in semen from subfertile men with leukocytospermia (LCS) and without leukocytospermia (non-LCS) and their associations with sperm quality. Methods Semen samples were collected from 195 men who asked for a fertility evaluation. Infection with the above 6 pathogens was assessed in each sample. Sperm quality was compared in subfertile men with and without LCS. Results The LCS group had significantly decreased semen volume, sperm concentration, progressive motility, total motility and normal morphology. The infection rates of Ureaplasma urealyticum (Uuu), Ureaplasma parvum (Uup), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), herpes simplex virus-2 (HSV-2) and Neisseria gonorrhoeae (NG) were 8.7 %, 21.0 %, 8.2 %, 2.1 %, 3.6 %, 1.0 and 0 %, respectively. The STI detection rates of patients with LCS were higher than those of the non-LCS group (52.3 % vs. 39.3 %), although there was no statistically significant difference between the two groups (P = 0.07). All semen parameters were not significantly different between LCS with STIs and without STIs, except the semen volume in the MG-infected patients with LCS was significantly lower than that in the noninfected group. Conclusions LCS was associated with a reduction in semen quality, but was not associated with STIs.

Abstract Objective The objective of this study was to determine fetal foramen ovale blood flow utilizing pulsed Doppler combined with spatiotemporal image correlation. Methods A cross-sectional study was performed in 440 normal fetuses between 20 and 40 weeks of gestation. In order to calculate foramen ovale blood flow, the foramen ovale flow velocity–time integral was obtained by pulsed Doppler ultrasonography, and the foramen ovale area was measured by using spatiotemporal image correlation rendering mode. Foramen ovale blood flow was calculated as the product of the foramen ovale area and the velocity–time integral. Results Gestational age-specific reference ranges are given for the absolute blood flow (ml/min) of foramen ovale, showing an exponential increase from 20 to 30 weeks of gestation, and a flat growth trend during the last trimester, while the weight-indexed flow (ml/min/kg) of foramen ovale decreased significantly. The median weight-indexed foramen ovale blood flow was 320.82 ml/min/kg (mean 319.1 ml/min/kg; SD 106.33 ml/min/kg). Conclusions The reference range for fetal foramen ovale blood flow was determined from 20 to 40 weeks of gestation. The present data show that the volume of foramen ovale blood flow might have a limited capacity to increase during the last trimester.

AimsTo explore the predictors of mucosal healing (MH) for short- and long-term after exclusive enteral nutrition (EEN) in pediatric Crohn’s disease (CD) patients.MethodsA retrospective analysis was performed for newly diagnosed active CD patients admitted to our center from January 2017 to 30 December 2020, who were treated with EEN for induction therapy with a minimum of 12 months of follow-up post-EEN. According to the simple endoscopic score for CD (SES-CD), at 1-year post-EEN, 17 patients with an SES-CD < 3 were classified into the sustained MH group (sMH), and 33 patients with an SES-CD ≥ 3 were classified into the sustained non-MH group (sNMH). Statistical methods were used to compare the differences between the two groups and explore the predictors of MH at the end of EEN and 1-year post-EEN.ResultsThe SES-CD in the sMH group was lower than that in the sNMH group both at baseline and the end of EEN [sMH vs. sNMH: 8.7 ± 1.2 vs. 16.2 ± 1.0, respectively, p < 0.001 at baseline; 1.0 (3.5) vs. 4.0 (2.0), respectively, p < 0.01 at the end of EEN]. The weighted Pediatric Crohn’s Disease Activity Index and erythrocyte sedimentation rate in the sMH group were lower than those in the sNMH group at baseline (both p < 0.05), but showed no difference at the end of EEN. From baseline to 1-year post-EEN, compared with patients in the sNMH group, there were more patients classified with L1 in the sMH group at each time point (all p < 0.001) and fewer patients classified with L3 in the sMH group at baseline and 1-year post-EEN. After EEN, fewer patients received infliximab and had a longer exposure time to infliximab in the sMH group than in the sNMH group. Only the SES-CD at baseline was negatively associated with MH at the end of EEN (OR = 1.40 95% CI = 1.12–1.67, p = 0.00) and 1-year post-EEN (OR = 1.33, 95% CI = 1.12–1.58, p = 0.001), and the cut off value was 11.5.ConclusionThe SES-CD could predict both short- and long-term MH for EEN. Patients with an SES-CD < 11.5 had a high probability of reaching MH by EEN-inducing therapy and maintaining sustained MH at 1-year post-EEN. Patients with an SES-CD greater than 11.5 at baseline should be treated more aggressively with biologics.

Abstract Background The fetal adrenal gland is a highly vascularized organs and develops two recognizable distinct zones in uetro, inner fetal zone (FZ) and outer definitive zone (DZ). Based on the region supplied, middle adrenal artery (MAA) mainly contribute to FZ while inferior adrenal artery (IAA) mainly to the inferior part of DZ. The purpose of this study was to establish reference ranges of adrenal artery Doppler indices of IAA and MAA, and assess zonal difference of blood supply to fetal adrenal gland. Methods The pulsatility index (PI), resistance index (RI), and systolic:diastolic ratio (S/D) of the IAA and MAA were obtained serially at 4-week intervals in normal fetuses. The MAA and IAA were referred based on the course and location in the gland: IAA referring the artery that mainly branches from the renal artery and walks along the renal upper pole, distributing the inferoposterior part of DZ in the adrenal gland while MAA as arterial blood flowing along the single central adrenal vein in the medial part of the gland. Multilevel modeling was performed to establish the gestational age-associated reference ranges for IAA and MAA. Differences in Doppler indices between the IAA and MAA were assessed. Results One hundred sixty-eight fetuses with 843 observations were included. The IAA had a higher detection rate than the MAA (100% vs 89.2%, p

Abstract Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related deaths worldwide. Overexpression of pleomorphic adenoma gene like‐2 (PLAGL2) is associated with tumorigenesis. However, its function in HCC is unclear, and there are currently no anti‐HCC drugs that target PLAGL2. Drug repositioning may facilitate the development of PLAGL2‐targeted drug candidates. Methods The expression of PLAGL2 in HCC clinical tissue samples and HCC cell lines was analyzed by western blotting. The constructed HCC cell models were used to confirm the underlying function of PLAGL2 as a therapeutic target. Multiple in vitro and in vivo assays were conducted to determine the anti‐proliferative and apoptosis‐inducing effects of selenium sulfide (SeS2), which is clinically used for the treatment of seborrheic dermatitis and tinea versicolor. Results PLAGL2 expression was higher in HCC tumor tissues than in normal adjacent tissues. Its overexpression promoted the resistance of HCC cells of mitochondrial apoptosis through the regulation of the downstream C‐MET/STAT3 signaling axis. SeS2 exerted significant anti‐proliferative and apoptosis‐inducing effects on HCC cells in a PLAGL2‐dependent manner. Mechanistically, SeS2 suppressed C‐MET/STAT3, AKT/mTOR, and MAPK signaling and triggered Bcl‐2/Cyto C/Caspase‐mediated intrinsic mitochondrial apoptosis both in vitro and in vivo. Conclusions Our data reveal an important role of PLAGL2 in apoptosis resistance in HCC and highlight the potential of using SeS2 as a PLAGL2 inhibitor in patients with HCC.

Although the thin endometrium (TE) has been widely recognized as a critical factor in implantation failure, the contribution of miRNA–mRNA regulatory network to the development of disease etiology remains to be further elucidated. This study performed an integrative analysis of the miRNA–mRNA expression profiles in the thin and adjacent normal endometrium of eight patients with intrauterine adhesion to construct the transcriptomic regulatory networks. A total of 1,093 differentially expressed genes (DEGs) and 72 differentially expressed miRNAs (DEMs) were identified in the thin adhesive endometrium of the TE group compared with the control adjacent normal endometrial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs and the target genes of DEM were significantly enriched in angiogenesis, cell growth regulation, and Wnt signaling pathway. Multiple hub genes (CAV1, MET, MAL2, has-mir-138, ARHGAP6, CLIC4, RRAS, AGFG1, has-mir-200, and has-mir-429) were identified by constructing the miRNA–mRNA regulatory networks. Furthermore, a miRNA–mRNA pathway function analysis was conducted, and the hub genes were enriched in the FoxO signaling pathway, cell growth regulation, inflammatory response regulation, and regulation of autophagy pathways. Our study is the first to perform integrated mRNA-seq and miRNA-seq analyses in the thin adhesive endometrium and the control adjacent normal endometrial cells. This study provides new insights into the molecular mechanisms underlying the formation of thin endometrium.