Federated attention consistent learning models for prostate cancer diagnosis and Gleason grading.

Artificial intelligence (AI) holds significant promise in transforming medical imaging, enhancing diagnostics, and refining treatment strategies. However, the reliance on extensive multicenter datasets for training AI models poses challenges due to privacy concerns. Federated learning provides a solution by facilitating collaborative model training across multiple centers without sharing raw data. This study introduces a federated attention-consistent learning (FACL) framework to address challenges associated with large-scale pathological images and data heterogeneity. FACL enhances model generalization by maximizing attention consistency between local clients and the server model. To ensure privacy and validate robustness, we incorporated differential privacy by introducing noise during parameter transfer. We assessed the effectiveness of FACL in cancer diagnosis and Gleason grading tasks using 19,461 whole-slide images of prostate cancer from multiple centers. In the diagnosis task, FACL achieved an area under the curve (AUC) of 0.9718, outperforming seven centers with an average AUC of 0.9499 when categories are relatively balanced. For the Gleason grading task, FACL attained a Kappa score of 0.8463, surpassing the average Kappa score of 0.7379 from six centers. In conclusion, FACL offers a robust, accurate, and cost-effective AI training model for prostate cancer pathology while maintaining effective data safeguards.

Concordance of assessments of four PD-L1 immunohistochemical assays in esophageal squamous cell carcinoma (ESCC).

OBJECTIVE: Given real-world limitations in programmed death-ligand 1 (PD-L1) testing, concordance studies between PD-L1 assays are needed. We undertook comparisons of PD-L1 assays (DAKO22C3, Ventana SP263, Ventana SP142, E1L3N) among observers in esophageal squamous cell carcinoma (ESCC) to provide information on the analytical and clinical comparability of four PD-L1 IHC assays. METHODS: Paraffin embedded samples of 50 cases of esophageal squamous cell carcinoma were obtained, satined with all four PD-L1 assays. PD-L1 was evaluated by 68 pathologists from 19 different hospitals. PD-L1 expression was assessed for combined positive score (CPS). RESULTS: The expression sensitivity of SP263 was the highest in ESCC, followed by 22C3, E1L3N and SP142. Taking CPS 10 as the critical value, inter-observer concordance for CPS scores among 68 physicians was assessed for the 22C3, SP263, SP142, and E1L3N assays, yielding values of 0.777, 0.790, 0.758, and 0.782, respectively. In the comparison between assays, the overall CPS scores concordance rates between 22C3 and SP263, SP142, and E1L3N were 0.896, 0.833, and 0.853, respectively. 22C3 and SP263 have high concordance, with OPA of 0.896, while E1L3N and SP142 have the highest concordance, with OPA of 0.908. CONCLUSION: In ESCC, the concordance of PD-L1 evaluation among observers is good, and the immune cell score is still an important factor affecting the concordance of interpretation among observers. Cases near the specific threshold are still the difficult problem of interpretation. SP263 had the highest CPS score of the four assays. SP263 cannot identify all 22C3 positive cases, but had good concordance with 22C3.E1L3N and SP142 showed high concordance.

Computed tomography radiomics identification of T1-2 and T3-4 stages of esophageal squamous cell carcinoma: two-dimensional or three-dimensional?

BACKGROUND: To evaluate two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) radiomics analysis for the T stage of esophageal squamous cell carcinoma (ESCC). METHODS: 398 patients with pathologically confirmed ESCC were divided into training and testing sets. All patients underwent chest CT scans preoperatively. For each tumor, based on CT images, a 2D region of interest (ROI) was outlined on the largest cross-sectional area, and a 3D ROI was outlined layer by layer on each section of the tumor. The radiomics platform was used for feature extraction. For feature selection, stepwise logistic regression was used. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the 2D radiomics model versus the 3D radiomics model. The differences were compared using the DeLong test. The value of the clinical utility of the two radiomics models was evaluated. RESULTS: 1595 radiomics features were extracted. After screening, two radiomics models were constructed. In the training set, the difference between the area under the curve (AUC) of the 2D radiomics model (AUC = 0.831) and the 3D radiomics model (AUC = 0.830) was not statistically significant (p = 0.973). In the testing set, the difference between the AUC of the 2D radiomics model (AUC = 0.807) and the 3D radiomics model (AUC = 0.797) was also not statistically significant (p = 0.748). A 2D model was equally useful as a 3D model in clinical situations. CONCLUSION: The performance of 2D radiomics model is comparable to that of 3D radiomics model in distinguishing between the T1-2 and T3-4 stages of ESCC. In addition, 2D radiomics model may be a more feasible option due to the shorter time required for segmenting the ROI.

Clinicopathological features and prognostic analysis of HER2 low and fibrotic focus in HER2-negative breast cancer.

OBJECTIVE: The aim of this study is to evaluate the clinicopathological features and prognostic significance of HER2 low, fibrotic focus (FF), and tumor-infiltrating lymphocytes (TILs) in patients with HER2-negative breast cancer. METHODS: We retrospectively reviewed the data of 293 patients with HER2-negative, stage I-II, invasive breast cancer of non-specific types. The HER2-negative cases were classified into HER2 low and HER2 0. Digital analysis of hematoxylin-eosin stained whole slide images was used to evaluate the FF expression. TILs were also evaluated using the Whole Slide Image. Furthermore, the association between HER2 low, FF, and TILs as well as their prognostic significance were analyzed. RESULTS: The study cohort included 178 cases (60.8%) with HER2 low and 115 cases (39.2%) with HER2 0. Older age, lower Nottingham histological grade (NHG), estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, and hormone receptor (HR) positivity were all associated with HER2 low. FF was correlated with older age, intermediate and low NHG, vascular invasion, HR positivity, HER2 low status, high Ki67 expression, and low TILs. Univariate survival analysis showed that FF was significantly associated with shorter progression-free survival (PFS). Stratified analysis indicated that in the HR-negative and HR-positive groups, HER2 status and TILs did not affect PFS. DFS was longer in patients without FF compared to those with FF in the HR-positive (hazard ratio [HR] = 0.313) and HER2 low (HR = 0.272) groups. DFS was also significantly longer in patients without FF compared to those with FF in the HR-negative (HR = 0.069) and HER2 0 groups (HR = 0.129). CONCLUSION: The results indicated that the HER2 low status and the TILs expression did not impact prognosis. However, patients with FF exhibited distinct biological characteristics and prognostic significance, particularly in the HR-negative and HER2 0 groups. This provides a rationale for accurate diagnosis and treatment of HER2-negative breast cancer.

[Mechanism of protective effect of resveratrol on poor ovarian response in mice].

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS.

OBJECTIVES: To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples. METHODS: The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode. RESULTS: The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%. CONCLUSIONS: The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

Multi-center study on predicting breast cancer lymph node status from core needle biopsy specimens using multi-modal and multi-instance deep learning.

The objective of our study is to develop a deep learning model based on clinicopathological data and digital pathological image of core needle biopsy specimens for predicting breast cancer lymph node metastasis. We collected 3701 patients from the Fourth Hospital of Hebei Medical University and 190 patients from four medical centers in Hebei Province. Integrating clinicopathological data and image features build multi-modal and multi-instance (MMMI) deep learning model to obtain the final prediction. For predicting with or without lymph node metastasis, the AUC was 0.770, 0.709, 0.809 based on the clinicopathological features, WSI and MMMI, respectively. For predicting four classification of lymph node status (no metastasis, isolated tumor cells (ITCs), micrometastasis, and macrometastasis), the prediction based on clinicopathological features, WSI and MMMI were compared. The AUC for no metastasis was 0.770, 0.709, 0.809, respectively; ITCs were 0.619, 0.531, 0.634, respectively; micrometastasis were 0.636, 0.617, 0.691, respectively; and macrometastasis were 0.748, 0.691, 0.758, respectively. The MMMI model achieved the highest prediction accuracy. For prediction of different molecular types of breast cancer, MMMI demonstrated a better prediction accuracy for any type of lymph node status, especially in the molecular type of triple negative breast cancer (TNBC). In the external validation sets, MMMI also showed better prediction accuracy in the four classification, with AUC of 0.725, 0.757, 0.525, and 0.708, respectively. Finally, we developed a breast cancer lymph node metastasis prediction model based on a MMMI model. Through all cases tests, the results showed that the overall prediction ability was high.

RT-qPCR is helpful to distinguish the clinicopathological features of HER2 immunohistochemistry 0 and 1.

The most commonly applied techniques to assess human epidermal growth factor receptor 2 (HER2) expression in breast cancer are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 detection by reverse transcription quantitative polymerase chain reaction (RT-qPCR) can provide standardized, objective and automated assessment and reflect the HER2 expression continuity. Currently, there is lack of sufficient evidence to validate whether RT­qPCR technique is more appropriate for the detection of HER2 low expression, especially ultra-low expression. Here, we primarily utilized RT-qPCR to differentiate HER2 true negative, ultra-low and 1 +, and compare the clinicopathological features and prognosis between RT-qPCR and IHC. 136 breast cancer cases with HER2 0 or 1 + were collected, also included 21 cases with HER2 2 + FISH negative as well as 25 cases with HER2 positive during the same period for comparative analysis. Compared the mRNA levels based on IHC/FISH scores. The receiver operating characteristic (ROC) curve was utilized to determine the threshold for reclassification, and the clinicopathological characteristics and prognosis differences among IHC true negative, ultra-low and 1 + after re-classification by RT-qPCR were analyzed. The mRNA level significantly differed between the IHC 0 and 1 + groups (p < 0.001). The IHC 0 group was further divided into true negative and ultra-low, there was no statistically significant difference in mRNA levels between true negative and ultra-low groups, while the difference between ultra-low and 1 + mRNA levels was statistically significant (p < 0.001). After reclassification of IHC true negative, ultra-low and 1 + by RT-qPCR, there were statistically significant differences in histological grade, ER, PR and TILs expression. There was no significant difference between DFS and OS in the two classification methods. RT-qPCR classification aids in distinguishing clinicopathological characteristics and can serve as a supplementary technique for detecting HER2-low by IHC.

Effect of extracapsular lymph node involvement on the prognosis of patients with esophageal squamous cell carcinoma.

BACKGROUND: According to the eighth edition of the tumor node metastasis (TNM) staging system for esophageal cancer, it is recommended that extracapsular lymph node involvement (EC-LNI) is included as a registered independent variable for the disease. However, its role in the prognosis has not been clearly explained. OBJECTIVE: To study the value of EC-LNI in the prognosis of esophageal cancer and attempt to explore its molecular mechanism via an enrichment analysis. METHODS: A retrospective analysis was performed on 544 patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery in the department of thoracic surgery of our hospital, focusing on the relationship between EC-LNI and clinicopathological characteristics and its effect on prognosis. Additionally, the mechanism of EC-LNI in esophageal cancer was explored. RESULTS: Among the 271 patients with lymph node metastasis, 125 were EC-LNI (+). The degrees of tumor differentiation, location, TNM stage, vascular tumor thrombus, and nerve invasion were related to the occurrence of EC-LNI. The stage of TNM was considered an independent risk factor for the development of EC-LNI. A significant difference was found in terms of overall survival (OS) and disease-free survival (DFS) between the EC-LNI (+) and EC-LNI (-) groups. A univariate analysis showed that the degrees of tumor differentiation, T stage, N stage, TNM stage, EC-LNI, EC-LNI number, and EC-LNI distance were significantly correlated with prognosis. A multivariate survival analysis showed that tumor differentiation, TNM stage, and EC-LNI were independent prognostic factors for OS, while TNM stage and EC-LNI were independent prognostic factors for DFS. The enrichment analysis identified the molecular targets and signaling pathways that can regulate cell proliferation, differentiation, and apoptosis. CONCLUSION: Extracapsular LNI has a high prognostic value in patients with esophageal cancer and is closely related to the stage of tumors. Our preliminary molecular mechanism research indicated that the molecular targets of EC-LNI are expected to become a new direction for the treatment of esophageal cancer.

Improved Alkaline Seawater Splitting of NiS Nanosheets by Iron Doping.

Seawater electrolysis driven by renewable electricity is deemed a promising and sustainable strategy for green hydrogen production, but it is still formidably challenging. Here, we report an iron-doped NiS nanosheet array on Ni foam (Fe-NiS/NF) as a high-performance and stable seawater splitting electrocatalyst. Such Fe-NiS/NF catalyst needs overpotentials of only 420 and 270 mV at 1000 mA cm-2 for the oxygen evolution reaction and hydrogen evolution reaction in alkaline seawater, respectively. Furthermore, its two-electrode electrolyzer needs a cell voltage of 1.88 V for 1000 mA cm-2 with 50 h of long-term electrochemical durability in alkaline seawater. Additionally, in situ electrochemical Raman and infrared spectroscopy were employed to detect the reconstitution process of NiOOH and the generation of oxygen intermediates under reaction conditions.

The Role of Artificial Intelligence in Accurate Interpretation of HER2 Immunohistochemical Scores 0 and 1+ in Breast Cancer.

The new human epidermal growth factor receptor (HER)2-targeting antibody-drug conjugate offers the opportunity to treat patients with HER2-low breast cancer. Distinguishing HER2 immunohistochemical (IHC) scores of 0 and 1+ is not only critical but also challenging owing to HER2 heterogeneity and variability of observers. In this study, we aimed to increase the interpretation accuracy and consistency of HER2 IHC 0 and 1+ evaluation through assistance from an artificial intelligence (AI) algorithm. In addition, we examined the value of our AI algorithm in evaluating HER2 IHC scores in tumors with heterogeneity. AI-assisted interpretation consisted of AI algorithms and an augmenting reality module with a microscope. Fifteen pathologists (5 junior, 5 midlevel, and 5 senior) participated in this multi-institutional 2-round ring study that included 246 infiltrating duct carcinoma cases that were not otherwise specified. In round 1, pathologists analyzed 246 HER2 IHC slides by microscope without AI assistance. After a 2-week washout period, the pathologists read the same slides with AI algorithm assistance and rendered the definitive results by adjusting to the AI algorithm. The accuracy of interpretation accuracy with AI assistance (0.93 vs 0.80), thereby the evaluation precision of HER2 0 and the recall of HER2 1+. In addition, the AI algorithm improved the total consistency (intraclass correlation coefficient = 0.542-0.812), especially in HER2 1+ cases. In cases with heterogeneity, accuracy improved significantly (0.68 to 0.89) and to a similar level as in cases without heterogeneity (accuracy, 0.97). Both accuracy and consistency improved more for junior pathologists than those for the midlevel and senior pathologists. To the best of our knowledge, this is the first study to show that the accuracy and consistency of HER2 IHC 0 and 1+ evaluation and the accuracy of HER2 IHC evaluation in breast cancers with heterogeneity can be significantly improved using AI-assisted interpretation.

Elective Transjugular Intrahepatic Portosystemic Shunt Using Viatorr Stent-Grafts: A Single-Center Experience from China.

Background and Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established approach for the management of variceal bleeding, refractory ascites, hepatic hydrothorax, and preoperative treatment of portal hypertension prior to major abdominal surgery in patients with compensated cirrhosis, and so on. This study aimed to investigate the safety and long-term efficacy of TIPS implantation using Viatorr TIPS stent-grafts. Material and Methods: A cohort of 59 patients undergoing TIPS placement using Viatorr TIPS stent-grafts were included, and the periprocedural events, and long-term mortality, shunt dysfunction, variceal rebleeding and incidence of hepatic encephalopathy (HE) were analyzed. Results: The technical success rate was 100%. The median portosystemic pressure gradient was reduced from 21 mmHg (interquatile range: 19-25) to 13 mmHg (interquatile range: 10-16) before and after TIPS, leading to a hemodynamic success rate of 72.9%. The cumulative rate of overall mortality was 34.2% at five years, and direct bilirubin (hazard ratio [HR] = 1.336, 95% confidence interval [CI]: 1.050-1.700, P = 0.018) and post-TIPS right atrial pressure (HR = 1.238, 95% CI: 1.015-1.510, P = 0.035) were independent predictors for mortality. The cumulative rates of shunt dysfunction and variceal rebleeding were 11.0% and 28.3% at five years, respectively, and portal venous pressure gradient (HR = 2.572, 95% CI: 1.094-6.047, P = 0.030) was the only independent predictor for shunt dysfunction. The cumulative four-year HE-free rate was 48.6%. No severe adverse event was noted during TIPS procedures. Conclusion: Elective TIPS implantation using Viatorr TIPS stent-grafts is generally safe, and the long-term efficacy is favorable for the treatment of cirrhotic patients with recurrent variceal bleeding or refractory ascites.

Can lymphovascular invasion be predicted by contrast-enhanced CT imaging features in patients with esophageal squamous cell carcinoma? A preliminary retrospective study.

BACKGROUND: To investigate the value of contrast-enhanced CT (CECT)-derived imaging features in predicting lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC) patients. METHODS: One hundred and ninety-seven patients with postoperative pathologically confirmed esophageal squamous cell carcinoma treated in our hospital between January 2017 and January 2019 were enrolled in our study, including fifty-nine patients with LVI and one hundred and thirty-eight patients without LVI. The CECT-derived imaging features of all patients were analyzed. The CECT-derived imaging features were divided into quantitative features and qualitative features. The quantitative features consisted of the CT attenuation value of the tumor (CTVTumor), the CT attenuation value of the normal esophageal wall (CTVNormal), the CT attenuation value ratio of the tumor-to-normal esophageal wall (TNR), the CT attenuation value difference between the tumor and normal esophageal wall (ΔTN), the maximum thickness of the tumor measured by CECT (Thickness), the maximum length of the tumor measured by CECT (Length), and the gross tumor volume measured by CECT (GTV). The qualitative features consisted of an enhancement pattern, tumor margin, enlarged blood supply or drainage vessels to the tumor (EVFDT), and tumor necrosis. For the clinicopathological characteristics and CECT-derived imaging feature analysis, the chi-squared test was used for categorical variables, the Mann-Whitney U test was used for continuous variables with a nonnormal distribution, and the independent sample t-test was used for the continuous variables with a normal distribution. The trend test was used for ordinal variables. The association between LVI status and CECT-derived imaging features was analyzed by univariable logistic analysis, followed by multivariable logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: The CTVTumor, TNR, ΔTN, Thickness, Length, and GTV in the group with LVI were higher than those in the group without LVI (P < 0.05). A higher proportion of patients with heterogeneous enhancement pattern, irregular tumor margin, EVFDT, and tumor necrosis were present in the group with LVI (P < 0.05). As revealed by the univariable logistic analysis, the CECT-derived imaging features, including CTVTumor, TNR, ΔTN and enhancement pattern, Thickness, Length, GTV, tumor margin, EVFDT, and tumor necrosis were associated with LVI status (P < 0.05). Only the TNR (OR 8.655; 95% CI 2.125-37.776), Thickness (OR 6.531; 95% CI 2.410-20.608), and tumor margin (OR 4.384; 95% CI 2.004-9.717) were independent risk factors for LVI in the multivariable logistic regression analysis. The ROC curve analysis incorporating the above three CECT-derived imaging features showed that the area under the curve obtained by the multivariable logistic regression model was 0.820 (95% CI 0.754-0.885). CONCLUSION: The CECT-derived imaging features, including TNR, Thickness, tumor margin, and their combination, can be used as predictors of LVI status for patients with ESCC.

Phytoestrogen arctigenin preserves the mucus barrier in inflammatory bowel diseases by inhibiting goblet cell apoptosis via the ERß/TRIM21/PHB1 pathway.

Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway-mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor ß (ERß) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERß knock down in the colons of mice with DSS-induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERß/TRIM21/PHB1 pathway.

Cystathionine ß-synthase expression correlates with tumor development and poor prognosis in patients with adenocarcinoma of the gastroesophageal junction.

OBJECTIVES: To reveal the expression level of cystathionine ß-synthase (CBS) in adenocarcinoma of esophagogastric junction (AEG) and discuss the relationship between CBS expression level and tumor microvascular density (MVD), clinical features and prognosis. METHODS: Paraffin samples from 214 patients with AEG were selected to make pathological microchips. Immunohistochemistry was performed based on the microchips to detect the expression level of CBS and microvascular density (MVD) in cancer tissues and adjacent control tissues. Relationships between expression level of CBS and MVD, clinical characteristics and prognosis were analyzed. RESULTS: In total, 214 AEG cases were classified into three groups: CBS negative staining (n=26), low staining (n=44), and high staining (n=144). Quantitative alterations in CBS and CD31 expression were explored using immunohistochemistry. The 5-year recurrence rate of enrolled patients was followed up and found that CBS expression was significantly increased in tumor tissue compared with adjacent non-tumor tissue (P<0.0001). There were significant differences in microvascular density between the groups with negative and high CBS staining (P<0.0001), and between the groups with low and high CBS staining (P<0.0001). Univariate analysis revealed significant differences in tumor stage (P<0.0001), T stage (P=0.008), N stage (P=0.028), differentiation degree (P=0.037), and 5-year survival (P=0.0034) among the three groups. Multivariate logic regression analysis showed that increased CBS scores were associated with an increased probability of 5-year recurrence (P=0.018). Finally, different CBS expression levels were associated with disease-free survival in AEG patients. CONCLUSIONS: CBS expression level is closely related to microvascular density and tumor stage in AEG. High level of CBS not only accelerates tumor angiogenesis but also affects patient's survival and prognosis.

Relationship between the changes of positivity rate of HER2 expression and the diameter of invasive lesions in early breast cancer and its clinical significance.

BACKGROUND: The expression status of HER2 is an important factor in evaluating the prognosis of breast cancer. We found that the positivity rate of HER2 varied with the diameter of invasive lesions in early breast cancer.We aimed to explore the relationship between the change of HER2 positivity rate of early breast cancer and the diameter of the invasive foci and its clinical significance. METHODS: A total of 217 patients with microinvasive breast cancer and T1a stage breast cancer were enrolled in this study. Machine learning algorithm was used to extract morphological features of invasive lesions in early breast cancer. Using Spearman to analysis the clinicopathological and morphological features related to HER2 expression McNemar test was used to analyze the consistency of HER2 expression between the carcinoma in situ area and the invasive cancer area. RESULTS: In early breast cancer, the diameter of the invasive foci was strongly negatively correlated with the expression status of HER2 (rho=-0.468, p < 0.001). As the diameter of the invasive foci increases, the HER2 positivity rate gradually decreases. When the diameter of the invasive foci> 2 mm, the positivity rate of HER2 was significantly reduced (from 52.6% to 16.1%, p < 0.001), which was close to the positivity rate of HER2 in ordinary invasive breast cancer. Moreover, most of the clinicopathological characteristics of breast cancer with an invasive lesion diameter of 1-2 mm and DCIS-MI were not significantly different (p > 0.05). Among 217 patients, the consistency rate of HER2 expression in carcinoma in situ and invasive foci areas was 97.7% (212/217), and there was no significant difference in HER2 expression status (p = 0.25 and p = 0.50, respectively). CONCLUSIONS: We recommend that breast cancer with an invasive lesion diameter of 1-2 mm should be classified as microinvasive breast cancer. In early breast cancer,the expression status of HER2 in the invasive foci area can refer to the HER2 expression status in carcinoma in situ area. However, it needs further support from a large amount of data and follow-up results.

Clinical Outcomes of Transjugular Intrahepatic Portosystemic Shunt (Tips) Creation Using Fluency Versus Viatorr Stent-Grafts: A Single-Centre Retrospective Study.

PURPOSE: To investigate the effects of transjugular intrahepatic portosystemic shunt (TIPS) creation using Fluency versus Viatorr stent-grafts on the long-term clinical outcomes. MATERIALS AND METHODS: This was a single-center retrospective study from January 2010 to October 2021 in 213 patients receiving TIPS with Fluency (Fluency group, n = 154) versus Viatorr (Viatorr group, n = 59) stent-grafts. Inclusion criteria were: age > 18 years old and TIPS creation for variceal hemorrhage. Exclusion criteria were: age > 80 years old, concomitant chronic heart or lung disease, active tuberculosis or human immunodeficiency virus infection, extrahepatic malignancy, alcohol dependence, TIPS created outside of our hospital, without any follow-up data, or decline to participate. The primary outcome was primary patency rate and its associated risk factors. RESULTS: The 5-year cumulative primary patency rate was significantly higher in Viatorr group than in Fluency group (89.0% vs. 19.6%, p < 0.001), whereas the 5-year cumulative transplant-free survival rate (62.3% vs. 62.2%, p = 0.636) was comparable between two groups. Cox-regression models revealed that group (hazard ratio [HR]4.029, 95% confidence interval [CI] 1.486-10.927, p = 0.006), use of bare stents (HR 3.307, 95% CI 1.903-5.747, p < 0.001), and baseline portal vein thrombosis (HR 0.248, 95% CI 0.149-0.412, p < 0.001) were significantly associated with shunt patency. Incidences of adverse events were not significantly different between two groups (p > 0.05). CONCLUSIONS: TIPS creation using Viatorr stent-grafts is superior to using Fluency stent-grafts in terms of higher long-term primary patency rate but similar transplant-free survival rate.

Circ_0006948 Contributes to Cell Growth, Migration, Invasion and Epithelial-Mesenchymal Transition in Esophageal Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) can act as promoters or inhibitors in cancer progression. Has_circ_0006948 (circ_0006948) was reported to aggravate the malignant behaviors of esophageal carcinoma (EC). AIMS: This study focused on investigating the molecular mechanism of circ_0006948 in EC progression. METHODS: The quantitative real-time polymerase chain reaction was performed to detect the expression of circ_0006948, microRNA-4262 (miR-4262) and fibronectin type III domain containing 3B (FNDC3B). Cell growth analysis was conducted by Cell Counting Kit-8 and colony formation assays. Cell migration and invasion were assessed by transwell assay. Epithelial-mesenchymal transition (EMT)-associated proteins and FNDC3B protein expression were assayed using western blot. Dual-luciferase reporter and RNA pull-down assays were performed to validate the target combination. Xenograft tumor assay was used for investigating the role of circ_0006948 in vivo. RESULTS: Circ_0006948 was upregulated in EC tissues and cells. Downregulating the expression of circ_0006948 or FNDC3B repressed cell growth, migration, invasion and EMT in EC cells. Target analysis indicated that miR-4262 was a target for circ_0006948 and FNDC3B was a downstream gene for miR-4262. Moreover, circ_0006948 could affect the expression of FNDC3B via sponging miR-4262. The effects of si-circ_0006948#1 on EC cells were partly restored by miR-4262 inhibition or FNDC3B overexpression. In addition, circ_0006948 also facilitated EC tumorigenesis in vivo by targeting the miR-4262/FNDC3B axis. CONCLUSION: Taken together, circ_0006948 functioned as an oncogenic factor in EC by the miR-4262-mediated FNDC3B expression regulation.

Reduced expression of microRNA-432-5p by DNA methyltransferase 3B leads to development of colorectal cancer through upregulation of CCND2.

BACKGROUND: The tumor suppressive function of microRNA-432-5p (miR-432-5p) has been reported in several human malignances. This study aimed to probe the expression profile and role of miR-432-5p in colorectal cancer (CRC) and the molecular mechanism. METHODS: Differentially expressed miRNAs between CRC and healthy samples were screened using a miRNA expression dataset GSE136020. The related molecules were identified by integrated bioinformatic analyses. A murine model of primary CRC was established and xenograft tumors were induced in mice. Altered expression of DNMT3B, miR-432-5p and cyclin D2 (CCND2) were introduced in CRC cells to determine their roles in the development of CRC. RESULTS: miR-432-5p was downregulated in CRC according to the GSE136020 dataset. CCND2 mRNA was confirmed as a target of miR-432-5p. miR-432-5p was downregulated, whereas CCND2 was abundantly expressed in CRC tissues and cells. DNA methyltransferase 3B (DNMT3B) induced DNA methylation at the CpG island of miR-432-5p to inhibit its expression. miR-432-5p mimic significantly suppressed tumorigenesis of primary CRC in mice. Downregulation of DNMT3B weakened viability, invasiveness, blocked the cell cycle progression of CRC cells in vitro, and inhibited xenograft tumor growth and metastasis in nude mice. However, additional downregulation of miR-432-5p or upregulation of CCND2 restored the malignant behaviors of CRC cells. CONCLUSION: This study showed that DNMT3B induced DNA methylation and downregulation of miR-432-5p to promote development of CRC by upregulating CCND2.

[Retracted] Downregulation of microRNA­629­5p in colorectal cancer and prevention of the malignant phenotype by direct targeting of low­density lipoprotein receptor­related protein 6.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data featured in Fig. 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 44: 1139­1150, 2019; DOI: 10.3892/ijmm.2019.4245].