Effect of Liver Segments and Hepatic Fibrosis Grade on Repeatability, Reliability, and Diagnostic Efficiency of Intravoxel Incoherent Motion.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is considered a potential marker of hepatic fibrosis (HF). OBJECTIVE: To explore the influencing factors of repeatability and reliability in IVIM-DWI parameters of ROI-based liver segments in participants with HF and healthy volunteers (HV) and to assess the diagnostic efficiency of these parameters in HF. METHODS: Participants with early HF (EHF, n=59) or advanced HF (AHF, n=38) and HV (n=48) were recruited. Two examiners measured IVIM data using mono-, bi-exponential and stretched exponential models. The results and influencing factors of repeatability and reliability of IVIM-DWI, and the diagnostic efficiency were analyzed. RESULTS: The repeatability of D* (CV: 26.62-41.47%) and DDC (CV: 18.01-34.40%) was poor, the repeatability of ADC (CV: 4.95-9.76%), D (CV: 7.09-15.52%), f (CV: 9.35-17.15%), and α (CV: 7.48-13.81%) was better; ordered logistic regression showed statistically significant results of IVIM-derived parameters; the reliability showed no obvious trend, and ordered logistic regression showed statistically significant results of IVIMderived parameters, groups, and partial hepatic segments (all p<0.001). IVIM-derived parameters with relatively good repeatability (CV<20%) and reliability (ICC>0.4) were used to establish regression models for differential diagnosis. The AUC of regression models was 0.744-0.783 (EHF vs. AHF), but no statistically significant parameters were found in the HV vs EHF comparison. CONCLUSION: IVIM-derived parameters were the most important factors affecting the repeatability and reliability, while staging of HF and hepatic segments may be the influencing factors of reliability. IVIM-derived parameters showed medium diagnostic efficiency in distinguishing between EHF and AHF.

Analytical and Clinical Evaluation of a Chemiluminescent Immunoassay to Detect Serum Chitinase-3-like Protein 1 in HBV-Related Liver Diseases.

Serum chitinase-3-like protein 1 (CHI3L1) is a diagnostic marker for liver diseases, such as hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the analytical performance of a chemiluminescent immunoassay (CLIA) for the quantitative detection of CHI3L1 and its application in hepatitis B virus (HBV)-related liver diseases. The CLIA for CHI3L1 detection presented good analytical performance, with a linear range of 1.50-2000.00 ng/mL and a detection limit of 0.98 ng/mL. To evaluate its clinical application, serum CHI3L1 levels were detected in 82 patients with chronic hepatitis B (CHB) and in 21 healthy controls. The patients with CHB and HCC had higher CHI3L1 levels than the healthy controls and the patients with CHB without HCC. However, CHI3L1 levels did not change significantly with the increase in liver fibrosis stages. The area under the receiver operating characteristic curve for the diagnosis of HBV-related HCC was 0.808, representing a moderate diagnostic value. Correlation analysis revealed a significant association between CHI3L1 and alpha-fetoprotein (AFP) levels, the fibrosis-4 (FIB-4) index, and the aspartate aminotransferase-to-platelet ratio index (APRI). In conclusion, compared with currently reported methods for CHI3L1 detection, the CLIA has a high sensitivity, a wide linear range, and an acceptable accuracy, precision, and reference intervals, making it valuable in the diagnosis of HBV-related HCC.

Repurposing sodium stibogluconate as an uracil DNA glycosylase inhibitor against prostate cancer using a time-resolved oligonucleotide-based drug screening platform.

Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties.

Cystic renal mass screening: machine-learning-based radiomics on unenhanced computed tomography

PURPOSE: The present study compares the diagnostic performance of unenhanced computed tomography (CT) radiomics-based machine learning (ML) classifiers and a radiologist in cystic renal masses (CRMs). METHODS: Patients with pathologically diagnosed CRMs from two hospitals were enrolled in the study. Unenhanced CT radiomic features were extracted for ML modeling in the training set (Guangzhou; 162 CRMs, 85 malignant). Total tumor segmentation was performed by two radiologists. Features with intraclass correlation coefficients of >0.75 were screened using univariate analysis, least absolute shrinkage and selection operator, and bidirectional elimination to construct random forest (RF), decision tree (DT), and k-nearest neighbor (KNN) models. External validation was performed in the Zhuhai set (45 CRMs, 30 malignant). All images were assessed by a radiologist. The ML models were evaluated using calibration curves, decision curves, and receiver operating characteristic (ROC) curves. RESULTS: Of the 207 patients (102 women; 59.1 ± 11.5 years), 92 (41 women; 58.0 ± 13.7 years) had benign CRMs, and 115 (61 women; 59.8 ± 11.4 years) had malignant CRMs. The accuracy, sensitivity, and specificity of the radiologist's diagnoses were 85.5%, 84.2%, and 91.1%, respectively [area under the (ROC) curve (AUC), 0.87]. The ML classifiers showed similar sensitivity (94.2%-100%), specificity (94.7%-100%), and accuracy (94.3%-100%) in the training set. In the validation set, KNN showed better sensitivity, accuracy, and AUC than DT and RF but weaker specificity. Calibration and decision curves showed excellent and good results in the training and validation set, respectively. CONCLUSION: Unenhanced CT radiomics-based ML classifiers, especially KNN, may aid in screening CRMs.

Covalent inhibition of epidermal growth factor receptor using a long-lived iridium(III)-afatinib probe.

The overexpression and overactivation of epidermal growth factor receptor (EGFR) are frequently observed in human cancers, including squamous cell carcinoma and adenocarcinoma. In this study, a covalent EGFR probe was developed by conjugating afatinib to an iridium(III) scaffold. Complex 1 showed enhanced luminescence in living epidermoid squamous carcinoma A431 cells compared to other cell lines, via engaging EGFR as confirmed via CETSA and knockdown experiments. Moreover, complex 1 inhibited downstream targets of EGFR in cellulo with repression persisting after removal of the complex, indicating an irreversible mode of inhibition. Finally, complex 1 showed potent antiproliferative activity against A431 cells with comparable potency to afatinib alone. To our knowledge, complex 1 is the first EGFR covalent inhibitor based on an iridium scaffold reported in the literature, with the potential to be further explored as a theranostic agent in the future.

Field-of-view optimized and constrained undistorted single shot intravoxel incoherent motion diffusion-weighted imaging of the cervix during the menstrual cycle: A prospective study.

OBJECTIVE: To provide insight into the biological characteristics of the healthy cervix by defining intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters across the menstrual cycle. METHODS: Forty-three females of reproductive age (18-45 years old) were included in this prospective study. Conventional magnetic resonance imaging (MRI) and IVIM-DWI scans were performed at multiple time-points across the menstrual cycle: T1 (menses), T2 (follicular phase), T3 (luteal phase). Intra- and interobserver repeatability of the IVIM-DWI values were evaluated with intraclass correlation coefficients (ICC), and D* was excluded from the analyses due to poor repeatability. Differences in each IVIM-DWI parameter among T1, T2, and T3 were explored. Subjects were stratified by age and parity for subgroup analyses (younger [18 - < 30 years] vs. older [≥30-45 years]; parity 0 vs. parity 1 and 2). Correlations between subject age and IVIM-DWI parameters were assessed. The overlap for each IVIM-DWI parameter among T1, T2, and T3 was evaluated. RESULTS: ADC and D values of the cervix were significantly lower at T3 compared with T1 (p = 0.02 and 0.03) or T2 (p < 0.01 and < 0.01). In younger subjects (n = 26), ADC and D values were significantly lower at T3 compared with T1 (p < 0.01 and p = 0.02) or T2 (p = 0.03 and p = 0.04). In older subjects (n = 17), ADC values were significantly higher at T2 compared with T1 (p = 0.01) or T3 (p = 0.01). There were significant differences in ADC values at T1 in subgroup analyses stratified by age and parity (both p < 0.01). There was a moderate correlation between age and ADC values at T1. Overlap for IVIM-DWI parameters across the menstrual cycle was >50%. CONCLUSION: ADC and D values of the heathy cervix differed across the menstrual cycle. Age and parity may influence the ADC value.

Enhanced and unenhanced: Radiomics models for discriminating between benign and malignant cystic renal masses on CT images: A multi-center study.

BACKGROUND: Machine learning algorithms used to classify cystic renal masses (CRMs) nave not been applied to unenhanced CT images, and their diagnostic accuracy had not been compared against radiologists. METHOD: This retrospective study aimed to develop radiomics models that discriminate between benign and malignant CRMs in a triple phase computed tomography (CT) protocol and compare the diagnostic accuracy of the radiomics approach with experienced radiologists. Predictive models were established using a training set and validation set of unenhanced and enhanced (arterial phase [AP] and venous phase [VP]) CT images of benign and malignant CRMs. The diagnostic capabilities of the models and experienced radiologists were compared using Receiver Operating Characteristic (ROC) curves. RESULTS: On unenhanced, AP and VP CT images in the validation set, the AUC, specificity, sensitivity and accuracy for discriminating between benign and malignant CRMs were 90.0 (95%CI: 81-98%), 90.0%, 90.5% and 90.2%; 93.0% (95%CI: 86-99%), 86.7%, 95.2% and 88.3%; and 95.0% (95%CI: 90%-100%), 93.3%, 90.5% and 92.1%, respectively, for the radiomics models. Diagnostic accuracy of the radiomics models differed significantly on unenhanced images in the training set vs. each radiologist (p = 0.001 and 0.003) but not in the validation set (p = 0.230 and 0.590); differed significantly on AP images in the validation set vs. each radiologist (p = 0.007 and 0.007) but not in the training set (p = 0.663 and 0.663); and there were no differences on VP images in the training or validation sets vs. each radiologist (training set: p = 0.453 and 0.051, validation set: p = 0.236 and 0.786). CONCLUSIONS: Radiomics models may have clinical utility for discriminating between benign and malignant CRMs on unenhanced and enhanced CT images. The performance of the radiomics model on unenhanced CT images was similar to experienced radiologists, implying it has potential as a screening and diagnostic tool for CRMs.

Field-of-view optimized and constrained undistorted single-shot study of intravoxel incoherent motion and diffusion-weighted imaging of the uterus during the menstrual cycle: a prospective study.

PURPOSE: This study aimed to compare the variability of the uterus during the menses phase (MP), follicular phase (FP), and luteal phase (LP) of the menstrual cycle using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). METHODS: This prospective study was conducted at the Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2022 and January 2023. Women of childbearing age (18-45 years) with appropriate progesterone levels were included in this study. Conventional magnetic resonance imaging and IVIM-DWI scans were performed during the MP, FP, and LP. The differences in IVIM-DWI-derived parameters between these phases were then compared, and the overlap was quantitatively described. RESULTS: The apparent diffusion coefficient (ADC) and pure molecular diffusion coefficient (D) values from the endometrium, uterine junctional zone (UJZ), and myometrium indicated statistical differences between the MP and FP and the MP and LP (ADC: endometrium, both P < 0.001; UJZ, P = 0.008 and P < 0.001, respectively; myometrium, P = 0.033 and P = 0.006, respectively; D: endometrium, both P < 0.001; UJZ, P = 0.008 and P = 0.006, respectively; myometrium, P = 0.041 and P = 0.045, respectively). The perfusion-related diffusion coefficient (D*) values from the myometrium indicated statistical differences between the FP and MP and the FP and LP (D*: myometrium, P = 0.049 and P = 0.009, respectively). The overlapping endometrium ratios between the MP and FP or LP were lower than 50% in the ADC and D values (ADC: overlapping of MP and FP: 33.33%, overlapping of MP and LP: 23.33%; D: overlapping of MP and FP: 40.00%, overlapping of MP and LP: 43.33%). CONCLUSION: The ADC and IVIM-derived parameters indicated differences in the uterus in diverse phases of the menstrual cycle, especially in the endometrium in relation to ADC and D values.

Diagnostic Value of Serum Chitinase-3-Like Protein 1 for Liver Fibrosis: A Meta-analysis.

Background: Serum chitinase-3-like protein 1 (CHI3L1) is a promising marker for diagnosing liver fibrosis. This meta-analysis was carried out to assess the diagnostic performance of serum CHI3L1 for the estimation of liver fibrosis. Methods: Systematic searches were performed on PubMed, Embase, Web of Science, Scopus, the Cochrane Library, Google Scholar, Sinomed, the China National Knowledge Infrastructure (CNKI), the Chinese Medical Journal Database, and the Wanfang databases for available studies. The primary studies were screened strictly according to inclusion and exclusion criteria, and sensitivity, specificity, and other measures of accuracy of serum CHI3L1 for evaluating liver fibrosis were pooled with 95% confidence intervals. I 2 was calculated to assess heterogeneity, and sources of heterogeneity were explored by subgroup analysis. Deeks' test was used to assess for publication bias, and likelihood ratio was used to determine posttest probability. Results: Our research integrated 11 articles, accounting for 1897 patients older than 18 years old. The pooled sensitivity and specificity for significant fibrosis, advanced fibrosis, and cirrhosis were 0.79 and 0.82 with an area under the receiver operating characteristic curve (AUC) of 0.85, 0.81 and 0.83 with an AUC of 0.91, and 0.72 and 0.74 with an AUC of 0.85, respectively. Random-effects models were used to assess for significant heterogeneity, and subgroup analysis showed that age and aetiology of included patients were likely sources of heterogeneity. No potential publication bias was found for serum CHI3L1 in the diagnosis of significant fibrosis, advanced fibrosis, or cirrhosis, and posttest probability was moderate. Conclusion: Measurement of serum CHI3L1 is a feasible diagnostic tool for liver fibrosis.

Clinicopathological characteristics and prognosis of gastrointestinal stromal tumors containing air-fluid levels.

An air-fluid level within a gastrointestinal stromal tumor (GIST) is unusual and indicates the presence of a fistula within the lumen of the GI tract. Until recently, the optimal management of such patients was not clear-cut. This retrospective study investigated the clinicopathological characteristics, surgical procedures, pre-and post-operative management, and prognosis of patients with GIST containing an air-fluid level. Data of GIST patients, spanning 5 years, including 17 GIST patients with air-fluid levels in the experimental group and 34 GIST patients without air-fluid levels in the control group, were retrieved from two hospitals in China. The clinicopathological characteristics, types of surgery, management, and clinical outcomes of GIST patients were compared between the two groups. GISTs containing air-fluid levels were significantly different from GISTs without air-fluid levels regarding tumor morphology, NIH risk category, invasion of adjacent organs, and necrosis or ulceration. Most GIST patients with air-fluid levels (14/17, 82.4%) received open surgery, significantly higher than the 20.6% in the control group. Targeted therapy with Imatinib mesylate (IM) was implemented in all GIST patients in the experimental group (17/17, 100%); markedly higher than those (3/34, 8.8%) in the control group. During follow-up, recurrence and death rates (5.9% and 5.9%) in the experimental group were higher than those (2.9% and 0%) in the control group. Open surgery is commonly performed in GIST patients with air-fluid levels who also require targeted therapy with IM. The Torricelli-Bernoulli sign could be a risk factor, adversely affecting the patient's prognosis.

Metastasis of missed cholangiocarcinoma in the left lobe through abdominal wall laparoscopic port-site and umbilicus after laparoscopic cholecystectomy: Case report and literature review.

Laparoscopic cholecystectomy (LC) has been widely used by surgeons. However, the missed diagnosis of intraperitoneal malignant tumor may occur. If the malignancy exists, the changes of the abdominal environment or the laparoscopic operation might brought the cancer cells to abdominal cavity or wall, to more extreme condition, will be located in the navel, which is known as Sister Mary Joseph's nodule(SMJN). A 63-year-old female who had undergone cholecystectomy and choledocholithotomy ten months ago was hospitalized for upper abdominal pain. Laboratory examination indicated that most of tumor markers were increased. CT revealed a progressively enhanced mass around the left lobe bile duct, multiple enlarged lymph nodes in the abdominal cavity and nodular lesions were found under the costal margin of the right side of abdominal wall and the umbilicus. Biopsy of the nodules under the original surgical scar showed middle differentiated adenocarcinoma. In laparoscopic cholecystectomy, surgeons should not only focus on the local lesions, but also look around other the tissues and organs to avoid missing the abdominal malignant tumor. When atypical symptoms or abnormalities have been found pre-operation, all abdominal organs should be evaluated in detail to avoid missed diagnosis of potential malignant tumors. On the other hand, when there is a nodule in the umbilicus, all organs in abdomen should be examined to find the potential malignant tumor. Finally, multiple cholelithiasis in the left lobe of the liver should be regarded as a high risk factor for cholangiocarcinoma.

Zinner syndrome: an updated pooled analysis based on 214 cases from 1999 to 2020: systematic review.

Zinner syndrome (ZS) is a rare anomaly of the Wolffian duct. We searched for case reports and case series to identify the most effective methods for examination and treatment. The PubMed/Medline, Embase, and Scopus databases were searched. Our searches yielded 160 case reports/case series and included 214 patients. The mean age at diagnosis was 29.35 years. The R:L distribution was 1:1. The most common symptoms were: frequency (24.3%), dysuria (23.1%) and perineal pain (20.2%) in ZS patients with clinical symptoms. The diagnostic investigations used most frequently were magnetic resonance imaging (MRI) (67.8%) and ultrasonography (65.0%). Maximum flow rate on uroflowmetry, semen ejaculate volume, sperm count, and sperm motility were significantly lower in patients with ZS. Among 193 patients with treatment details, 65.8% underwent surgery; 9.8% underwent aspiration; 24.3% were followed with observation. Two patients died after surgery; all other patients remained asymptomatic after surgery. Fifty-two patients had complications and comorbidities. In patients with ZS, the most common symptoms are seminal vesicle cyst enlargement and compression of the bladder, ureter, and reproductive system. The diagnosis mostly depends on radiological examination. Surgery may be effective, but complications may occur.

[CT imaging features and misdiagnosis analysis of occult anterior calcaneal process fracture].

OBJECTIVE: To explore CT imaging features and reason for missed diagnosis of clinical practice of occult anterior calcaneal process fracture. METHODS: From July 2013 to November 2018, the clinical data of 13 patients with occult an anterior calcaneal process fracture were retrospectively analyzed, including 2 males and 11 females, aged from 22 to 54 years old. Classification of fracture, displacement of fracture, direction of fracture line, size of fracture, with or without tarsal coalition, other fractures and misdiagnosis, the time from injury to diagnosis, condition of treatment and fracture healing were observed according to case history, data of X-ray and CT. RESULTS: Thirteen patients were diagnosed as occult anterior calcaneal process fracture after CT examination. According to Degan classification, 9 patients were type I, 4 patients were typeII; 4 patients were occurred displacement, and 9 patients did not occurred displacement. On the horizontally CT, fracture line of 12 patients showed transverse, 1 patient oblique, and the size of fracture ranged from 0.40 to 1.72 cm; while on the sagittal view, fracture line of 12 patients showed vertical, 1 patient oblique, and the size of fracture ranged from 0.10 to 0.59 cm. No patients combined with talocalcaneal and scaphoid bridge. Six patients were simple anterior calcaneal process fracture, 7 patients combined with other fractures. Eight patients were misdiagnosed. The time from injury to diagnose ranged from 0 to 21 days. Nine patients with type Iwere performed conservative treatment, 6 patients healed well and 3 patients with fracture line less than 1 cm on horizontally view occurred fracture nonunion. Four patients with type II did not perform operation, and fracture were not union, regardless of fracture size. CONCLUSIONS: Occult anterior calcaneal process fracture have high rate of missed diagnosis in clinical practice. CT imaging features of fracture showed that most fracture line were transverse on CT horizontal plane while vertical on CT sagittal plane, as well as small side of fragment on CT sagittal plane with differernt sizes of fragment on CT horizontal plane; type Ifracture with fragment less than 1 cm on CT horizontal plane and type II both have high rate of nonunion while treated with conservative treatment.