Modulating PCGF4 Stability Is an Efficient Metastasis-Regulatory Strategy Used by Distinct Subtypes of Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and prone to metastasis. It is unclear if cancer-associated fibroblasts (CAFs) affect the metastasis of ICC. Here, we have established ICC patient-derived CAF lines and related cancerous cell lines and analyzed the effects of CAFs on the tumor progressive properties of the ICC cancerous cells. Results demonstrated that CAFs can be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-sequencing analyses of ICC cancerous cell lines identified B-lymphoma Mo-MLV insertion region 1 (PCGF4; alias BMI1) as a potential metastasis regulator. Strikingly, the changes of PCGF4 levels in ICC cells perfectly mirrored the restraining or promoting effects of CAFs on ICC migration. Our immunohistochemical analyses on the ICC tissue microarrays indicated that PCGF4 was negatively correlated to overall survival of ICC. We confirmed the promoting effects of PCGF4 on cell migration, drug resistance activity, and stemness properties. Mechanistically, cancer-restraining CAFs triggered the proteasome-dependent degradation of PCGF4, whereas cancer-promoting CAFs enhanced the stability of PCGF4 via activating the IL-6/phosphorylated STAT3 pathway. In summary, our data identified roles of CAFs on ICC metastasis and revealed a new mechanism of the CAFs on ICC progression in which PCGF4 acted as the key effector by both categories of CAFs. These findings shed light on developing comprehensive therapeutic strategies for ICC.

A Review of deep learning methods for denoising of medical low-dose CT images.

To prevent patients from being exposed to excess of radiation in CT imaging, the most common solution is to decrease the radiation dose by reducing the X-ray, and thus the quality of the resulting low-dose CT images (LDCT) is degraded, as evidenced by more noise and streaking artifacts. Therefore, it is important to maintain high quality CT image while effectively reducing radiation dose. In recent years, with the rapid development of deep learning technology, deep learning-based LDCT denoising methods have become quite popular because of their data-driven and high-performance features to achieve excellent denoising results. However, to our knowledge, no relevant article has so far comprehensively introduced and reviewed advanced deep learning denoising methods such as Transformer structures in LDCT denoising tasks. Therefore, based on the literatures related to LDCT image denoising published from year 2016-2023, and in particular from 2020 to 2023, this study presents a systematic survey of current situation, and challenges and future research directions in LDCT image denoising field. Four types of denoising networks are classified according to the network structure: CNN-based, Encoder-Decoder-based, GAN-based, and Transformer-based denoising networks, and each type of denoising network is described and summarized from the perspectives of structural features and denoising performances. Representative deep-learning denoising methods for LDCT are experimentally compared and analyzed. The study results show that CNN-based denoising methods capture image details efficiently through multi-level convolution operation, demonstrating superior denoising effects and adaptivity. Encoder-decoder networks with MSE loss, achieve outstanding results in objective metrics. GANs based methods, employing innovative generators and discriminators, obtain denoised images that exhibit perceptually a closeness to NDCT. Transformer-based methods have potential for improving denoising performances due to their powerful capability in capturing global information. Challenges and opportunities for deep learning based LDCT denoising are analyzed, and future directions are also presented.

Involvement of gut-brain communication in arsenite-induced neurobehavioral impairments in adult male mice.

Arsenite is a well-documented neurotoxic metalloid that widely distributes in the natural environment. However, it remains largely unclear how arsenite affects neurological function. Therefore, in this study, the healthy adult male mice were exposed to 0.5 mg/L and 5 mg/L arsenite through drinking water for 30 and 90 days, respectively. Our results showed that there was no significant alteration in the intestine and brain for 30 days exposure, but exposure to arsenite for 90 days significantly induced a reduction of locomotor activity and anxiety-like behavior, caused pathological damage and inflammatory responses in the brain and intestine. We also found that arsenite remarkably disrupted intestinal barrier integrity, decreased the levels of lysozyme and digestive enzymes. Intriguingly, chronic exposure to arsenite significantly changed the levels of gut-brain peptides. Taken together, this study provides meaningful insights that gut-brain communication may involve in the neurobehavioral impairments of arsenite.

Effect of Taijiquan assisted rehabilitation for breast cancer patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Taijiquan, as a supplementary and alternative method, has attracted more and more attention in the treatment of breast cancer. But up to now, no systematic review has been performed to evaluate the efficacy of Taijiquan in the treatment of breast cancer. In this study, Cochrane systematic review method will be used to evaluate the effect of Taijiquan in the rehabilitation process of breast cancer patients after treatment. METHODS: PubMed, Embase. com, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and SinoMed will be searched to identify relevant studies up to May 31, 2021. We will include randomized controlled trials (RCTs) of the application of Taijiquan in post-treatment breast cancer patients. We will use the Cochrane bias risk assessment tool to assess the quality of included RCTs. We will use Stata 13.0 to perform pairwise meta-analyses using the inverse variance method. Subgroup analyses and sensitivity analyses will be conducted to investigate the sources of heterogeneity. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will comprehensively evaluate the efficacy of Taijiquan in the rehabilitation treatment of breast cancer. The results of this study will provide high-quality evidence to support clinical practice and guidelines development.

Study on the Effect of Capsaicin on the Intestinal Flora through High-Throughput Sequencing.

As a common kind of food, pepper is well known for its special effects on the physiological state of human individuals. Capsaicin, the main component of pepper, is speculated to be linked with intestinal microorganisms on account of their direct contact. Herein, we first utilized mouse models and 16S rRNA high-throughput sequencing to compare the differences in intestinal flora between mouse groups with and without capsaicin treatment by gavage. The mice in the two groups showed significantly distinct performance in terms of body weight, leukocyte count, fecal humidity, and constituent ratios of intestinal bacteria, such as Faecalibacterium, Akkermansia, Roseburia, Helicobacter, and Bacteroides species. In particular, the Faecalibacterium abundance was the most highly variable among the 5 bacterial genera. Based on statistical analysis and comparison, the variation tendency of body weight, leukocyte count, and fecal humidity was closely related to the bacteria. In conclusion, capsaicin could affect the physiological state of mice by changing the constitution of the intestinal flora.

MiR-142-3p targeting NUCKS1 inhibits proliferation and invasion of pancreatic cancer cells.

Objective: To investigate the effects of microRNA-142-3p (miR-142-3p) on the biological characteristics of pancreatic cancer cells and its mechanism.Methods: The expression of miR-142-3p and nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) in pancreatic tissues and four cancer cell lines (Panc-1, BxPC-3, AsPC-1, MIA-PaCa2) were detected by Quantitative PCR (qPCR) or Western blot. The cell viability of pancreatic cancer cells was examined by MTT assay. The apoptosis of pancreatic cancer cells was measured by flow cytometry. Transwell assay was utilized to test the migration and invasion of pancreatic cancer cells. Bioinformatics analysis for miR-142-3p was conducted and the dual luciferase reporter gene assay was utilized to further validate the predicted target relationship. The protein levels of PI3K, p-AKT and T-AKT were analyzed by Western blot.Results: The expression of miR-142-3p was down-regulated, while the expression of NUCKS1 was significantly up-regulated in pancreatic tissues and four cancer cell lines. The expression of miR-142-3p in pancreatic tissues was inversely correlated with NUCKS1 expression. Overexpression of miR-142-3p inhibited the cell viability, cell migration, and invasion, while promoted cell apoptosis of AsPC-1 and MIA-PaCa2 cells. MiR-142-3p targeted NUCKS1 and negatively regulated NUCKS1. Overexpression of miR-142-3p decreased PI3K and p-AKT expression. Up-regulation of NUCKS1 partially reversed the effects of the overexpression of miR-142-3p on the cell viability, cell apoptosis, migration and invasion, as well as PI3K and p-AKT expression in AsPC-1 and MIA-PaCa2 cells.Conclusion: MiR-142-3p regulated the biological characteristics of pancreatic cancer cells by directly targeting NUCKS1.

[Risk factors of portal vein thrombosis after surgery for advanced schistosomiasis portal hypertension].

OBJECTIVE: To explore the risk factors of portal vein thrombosis (PVT) after splenectomy and esophagogastric devascularization for advanced schistosomiasis portal hypertension. METHODS: The clinical data were collected retrospectively from 211 advanced schistosomiasis portal hypertension patients after splenectomy and esophagogastric devascularization from August, 2004 to March 2014, and all the data were analyzed statistically for the risk factors of PVT after the surgery by single factor analysis and Logistic regression analysis. RESULTS: Totally 59 patients were found with PVT and the incidence was 27.96% (59/211). The single factor analysis showed that 8 factors were related to PVT after surgery, including the history of upper gastrointestinal hemorrhage, the diameter of portal vein, the diameter of splenic vein, esophageal varices, ascites, portal hypertension gastropathy, gastric varices , and blood ammonia level. The Logistic regression analysis showed that the independent risk factors of PVT were broadening of the diameter of portal vein (OR = 1.763 , P = 0.000) and portal hypertension gastropathy (OR = 1.089, P = 0.037). CONCLUSIONS: The incidence of PVT after surgery for advanced schistosomiasis is high, and the independent risk factors are broadening of diameter of portal vein and portal hypertension gastropathy.