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Background: Preservation fluid (PF) contamination, especially by multidrug‐resistant (MDR) Gram‐negative bacteria (GNB), poses a high risk of donor‐derived infection (DDI) and severe clinical outcomes. We sought to determine whether the use of colistin sulfate to decontaminate PF in kidney transplantation can decrease the incidence of probable DDI (p‐DDI) caused by MDR GNB. Methods: In a retrospective study of 916 recipients who received deceased donation, 864 PF samples were collected and cultured, and microbiological contaminants were recorded with the recipients' clinical data and outcomes. From March 2016 to May 2019, 624 samples were decontaminated with ceftizoxime, and from June 2019 to March 2021, 240 samples were decontaminated with colistin sulfate. Between‐group comparisons were performed to assess the ability of the two decontamination regimens to decrease the incidence of p‐DDI, especially MDR GNB‐related infection. Results: The overall PF contamination rate was 54.51% (471/864), and 80 samples were positive for MDR GNB contamination. All p‐DDIs occurred in the ceftizoxime group (p < 0.001), and 67.65% of p‐DDIs were MDR GNB‐related. In the ceftizoxime group, 23 of 61 cases of MDR GNB contamination led to related p‐DDIs, while none occurred in the colistin sulfate group (p = 0.002). Among the 23 patients with p‐DDIs, 5 died due to severe infection, and 2 experienced graft loss. Conclusions: The goal of decontamination should be to decrease the risk of MDR GNB‐related p‐DDI, and colistin sulfate could be an effective and feasible option. [ABSTRACT FROM AUTHOR]

Background. The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. Method. Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. Results. X-tile plots identified 3 (P < 0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P < 0.001 , P = 0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P < 0.001). Conclusion. More TD count (TD count ≥ 4) was significantly associated with poor disease-specific survival in CRC patients. [ABSTRACT FROM AUTHOR]

Background and Objective: Hepatocyte nuclear factor 3β (HNF3β) is a key transcription factor in the development of the gastrointestinal tract. However, only few studies have examined its' expression, function and potential clinical significance in colorectal cancer tumorigenesis and progression. Methods: HNF3β expression in colorectal cancer tissue samples of 174 patients was assessed by immunohistochemistry. The results were analyzed with respect to patients' clinicopathological characteristics and survival. Following the in vitro cell transfection, MTT, wound healing, and Transwell assays were used to test cell proliferation, migration, and invasion, respectively. Western blot was used to examine IL6, JAK1, and STAT3 protein expression. The potential for tumor formation was evaluated using a mouse xenograft model. Results: HNF3β expression was lower in colon cancer tissue compared to normal tissue and correlated with UICC clinical stage (P = 0.001), depth of invasion (P = 0.004), regional lymph node metastasis (P = 0.007), distant metastasis (P = 0.048), and poor survival (P < 0.001) in patients with colorectal cancer. Furthermore, HNF3β overexpression impeded proliferation, migration and invasion of SW480 cells via JAK-STAT3 signaling in vitro. Moreso, HNF3β overexpression showed a significant growth inhibition of subcutaneous xenograft tumors in vivo. Conclusions: The results show that HNF3β acts as a suppressor of colorectal cancer progression and decreased HNF3 β expression is closely related to the poor prognosis. Thus, HNF3β may be a potential molecular target for inhibition of colorectal cancer cells and development of new anti-tumor therapies. [ABSTRACT FROM AUTHOR]

Alsterpaullone (Alp) is a small-molecule inhibitor that targets cyclin-dependent kinases to inhibit tumor cell activity. However, to the best of our knowledge, the effect of Alp on hepatoblastoma has not been investigated. Therefore, the function of Alp in apoptotic induction of hepatoblastoma cells and a potential mechanism of action were investigated. Results indicated that low doses of Alp (1 µM) significantly induced apoptosis in the HepG2 hepatoblastoma cell line. In vivo experiments of tumor suppression further indicated that Alp (3 mg/kg) exerted an inhibitory effect on HepG2 ×enograft tumor growth. Following Alp treatment, the expression level of B-cell lymphoma 2 (Bcl-2)-associated X protein, and cleaved caspase-3 and −9 in HepG2 cells was significantly increased; however, the expression of Bcl-2 was significantly decreased. In addition, phosphorylation of p38 mitogen-activated protein kinase (MAPK) significantly decreased Alp-induced caspase-3 and −9 activation. These results suggested that Alp induces apoptosis and inhibited proliferation via the p38MAPK signaling pathway. Therefore, Alp may be a therapeutic agent for treating hepatoblastoma. [ABSTRACT FROM AUTHOR]

Schisantherin A (SchA) is a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera . The role of SchA in liver injury induced by ischemia and reperfusion (I/R) has not yet been elucidated. The present study hypothesized the protective effects of SchA in hepatic I/R model. Either sham laparotomy or hepatic I/R was induced in C57BL/6 male mice after SchA or vehicle administration. Liver function, histological damage, oxidative/nitrosative stress, inflammatory infiltration, cytokine production, cell apoptosis, cell autophagy, and I/R-associated intracellular signaling pathway were assessed to evaluate the impact of SchA pretreatment on I/R-induced liver injury. After liver I/R injury, the mice pretreated with appropriate SchA displayed significantly preserved liver function, less histological damage, ameliorated oxidative/nitrosative stress, attenuated inflammatory state, and reduced cell apoptosis. However, no differences in the autophagic response were detected after SchA pretreatment. The underlying protective mechanism putatively involves the inhibition of mitogen-activated protein kinase (MAPK) signaling pathway. Based on the beneficial effects, SchA pretreatment may serve as a potential prophylactic measure to prevent liver I/R injury related to various clinical conditions. [ABSTRACT FROM AUTHOR]

Objective: To assess the prognostic value of a model based on pre-treatment T2WI-based radiomic features and postoperative pathological staging in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy., Methods: Radiomic features were derived from T2WI, and a radiomic signature (RS) was established and validated for the prediction of distant metastases (DM). Subsequently, we designed and validated a nomogram model that combined the radiomic signature and postoperative pathological staging for enhanced DM prediction. Performance measures such as the concordance index (C-index) and area under the curve (AUC) were computed to assess the predictive accuracy of the models., Results: A total of 260 patients participated in this study, of whom 197 (75.8%) were male, and the mean age was 57.2 years with a standard deviation of 11.2 years. 15 radiomic features were selected to define the radiomic signature. Patients with a high-risk radiomic signature demonstrated significantly shorter distant metastasis-free survival (DMFS) in both the development and validation cohorts. A nomogram, incorporating the radiomic signature, pathological T stage, and N stage, achieved an area under the curve (AUC) value of 0.72 (95% CI, 0.60-0.83) in the development cohort and 0.83 (95% CI, 0.73-0.92) in the validation cohort., Conclusion: A radiomic signature derived from T2WI-based radiomic features can effectively distinguish patients with varying risks of DM. Furthermore, a nomogram integrating the radiomic signature and postoperative pathological stage proves to be a robust predictor of DMFS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Chen, Zheng, Zheng, Zhou, Zhang and Zhang.)

Background: With the elimination of schistosomiasis in China, its role in the pathogenesis of colorectal cancer (CRC) has decreased. However, the trends, clinicopathological features, surgical treatment patterns, and prognosis of schistosomiasis-associated CRC (SACRC) versus non-schistosomiasis-associated CRC (NSACRC) in China remain unclear., Materials and Methods: The percentage trend of SACRC in CRC patients in China was analyzed using data retrieved from the Pathology Registry of Changhai Hospital (2001-2021). Clinicopathological characteristics, surgical treatment patterns, and prognosis-related parameters were compared between the two groups. Multivariate Cox regression analyses were performed for disease-free survival (DFS) and overall survival (OS)., Results: A total of 31 153 CRC cases were included, with 823 (2.6%) cases of SACRC and 30 330 (97.4%) cases of NSACRC. The average percentage of SACRC cases has decreased continuously from 3.8 to 1.7% (from 2001 to 2021). Compared with the NSACRC group, the SACRC group had more men, older age at diagnosis, lower BMI, fewer symptoms; higher rates of rectal cancer, comorbidities, KRAS mutation, multiple primary CRC and concomitant polyps; less lymph node metastasis, distant metastasis, vascular invasion, and tumor budding; less preoperative radiotherapy and preoperative chemotherapy; and more positive resection margins and postoperative targeted therapy. There were no significant differences between the two groups regarding laparoscopic surgery, palliative resection, extended radical resection, or ostomy. Moreover, the SACRC group had adverse DFS and similar OS compared with the NSACRC group. In multivariate analyses, schistosomiasis was not an independent predictor of DFS or OS., Conclusion: The percentage of SACRC in CRC (2.6%) in our hospital was very low, and it decreased continuously over the last two decades, indicating that schistosomiasis is no longer an important risk factor for CRC in Shanghai, China. Patients with SACRC have distinct clinicopathological, molecular, and treatment-related features and survival rates similar to those with NSACRC., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The tumor microenvironment (TME) plays a critical role in shaping tumor progression and determining the outcome of the therapeutic response. In this study, we aimed to generate a comprehensive cellular landscape of the colorectal cancer (CRC) TME., Methods: We generated a comprehensive single-cell atlas by collecting CRC cases that have been uploaded to the online database and conducting an in-depth secondary analysis. We then carried out spatial transcriptomic sequencing and multiple immunohistochemical analyses to verify the results of the single-cell analysis. Moreover, we applied our findings to the TCGA database and used tissue microarray (TMA) on CRC tissue specimens to validate clinical prognosis., Findings: We re-analyzed the transcriptomes of 23785 cells, revealing a pattern of cell heterogeneity in the tumor region, leading-edge region, and non-tumor region. A subtype of COL11A1+INHBA+ tumor-resident cancer-associated fibroblasts (CAFs) was identified, and marker genes, transcription factors, and tissue-specific expression differences were noted and suggested to have potential roles in promoting cancer. We further confirmed that COL11A1+INHBA+ tumor-resident CAFs are mainly located in the hypoxic TME and we propose that they interact with CD44+ CRC cells via INHBA. Elevation of INHBA in CRC is associated with a poor prognosis., Interpretation: Our results demonstrated a single cell landscape of CRC in different regions and identified in hypoxic TME a special subtype of CAFs producing INHBA, which promotes CRC development and correlates with poor prognosis. This special subtype of CAFs is a candidate target for translational research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Simultaneous resection for patients with synchronous colorectal cancer liver metastases (CRLM) remains an optimal option for the sake of curability. However, few studies so far focus on outcome of this subgroup of patients (who receive simultaneous resection for CRLM). Substantial heterogeneity exists among such patients and more precise categorization is needed preoperatively to identify those who may benefit more from surgery. In this study, we formulated this internally validated scoring system as an option., Methods: Clinicopathological and follow-up data of 234 eligible CRLM patients undergoing simultaneous resection from January 2010 to March 2019 in our center were included for analysis. Patients were randomized to either a training or validation cohort. We performed multivariable Cox regression analysis to determine preoperative factors with prognostic significance using data in training cohort, and a nomogram scoring system was thus established. Time-dependent receiver operating characteristic (ROC) curve and calibration plot were adopted to evaluate the predictive power of our risk model., Results: In the multivariable Cox regression analysis, five factors including presence of node-positive primary defined by enhanced CT/MR, preoperative CEA level, primary tumor location, tumor grade and number of liver metastases were identified as independent prognostic indicators of overall survival (OS) and adopted to formulate the nomogram. In the training cohort, calibration plot graphically showed good fitness between estimated and actual 1- and 3-year OS. Time-dependent ROC curve by Kaplan-Meier method showed that our nomogram model was superior to widely used Fong's score in prediction of 1- and 3-year OS (AUC 0.702 vs. 0.591 and 0.848 vs. 0.801 for 1- and 3-year prediction in validation cohort, respectively). Kaplan-Meier curves for patients stratified by the assessment of nomogram showed great discriminability (P<0.001)., Conclusions: In this retrospective analysis we identified several preoperative factors affecting survival of synchronous CRLM patients undergoing simultaneous resection. We also constructed and validated a risk model which showed high accuracy in predicting 1- and 3-year survival after surgery. Our risk model is expected to serve as a predictive tool for CRLM patients receiving simultaneous resection and assist physicians to make treatment decision., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-329). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

In this study, we explored the actions of miR-199a/b-5p during hepatocellular carcinoma (HCC) progression and its potential target genes. Through heatmap miRNA expression analysis of 15 matched HCC tumor and adjacent non-tumor liver tissues from the TCGA database, we detected 19 mRNAs that were upregulated and 13 that were downregulated specifically in HCC. Among these, miR-199 family members were downregulated in HCC tumors and cell lines, as compared to controls. Low miR-199a/b-5p expression was also associated with poor overall survival of HCC patients. miR-199a/b-5p overexpression in HCC cell lines inhibited cell proliferation, migration and invasion, both in vitro and in vivo . In addition, miR199-a/b-5p post-transcriptionally suppressed Rho-associated coiled-coil kinase 1 (ROCK1). This in turn led to inhibition of ROCK1/MLC and PI3K/Akt signaling, which is necessary for HCC proliferation and metastasis. These results indicate that miR-199a/b acts as tumor suppressors in HCC and represent promising therapeutic targets., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no actual or potential conflicts of interest.