Cancer-Associated Endocrine Cells Participate in Pancreatic Carcinogenesis.

BACKGROUND & AIMS: The pancreas is composed of endocrine and exocrine parts, and its interlacing structure indicates potential interaction between endocrine and exocrine cells. Although the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has been well characterized, the role of pancreatic endocrine cells during carcinogenesis is relatively understudied. METHODS: The changes of endocrine cells in PDAC by single-cell transcriptome sequencing, spatial transcriptome sequencing, and multiplex immunohistochemistry were depicted. After that, the interaction between pancreatic carcinogenesis and endocrine changes was explored in orthotopic transplantation mice, KrasLSL-G12DPdx1-Cre mice, and KrasLSL-G12Dp53LoxPPdx1-CreER mice. Finally, we proved the mechanism of the interaction between endocrine and exocrine parts of the pancreas through islet isolation, co-culture in vitro and co-injection in vivo. RESULTS: Pancreatic endocrine cells displayed significantly different transcriptomic characteristics and increased interaction with exocrine part in PDAC. Specifically, among all of the changes, pancreatic polypeptide-positive cells showed a sharp increment accompanied by the progression of the cancer lesion, which might be derived from the transdifferentiation of α and ß cells. Interestingly, it was proved that PDAC cells were able to induce the transdifferentiation of pancreatic α cells and ß cells into glucagon-pancreatic polypeptide and insulin-pancreatic polypeptide double-positive cells, which further promoted carcinogenesis and development of PDAC in a paracrine-dependent manner and formed a reciprocal interaction. CONCLUSIONS: This study systematically maps the alteration of pancreatic endocrine cells in PDAC and elucidates the potential endocrine-exocrine interaction mechanisms during PDAC carcinogenesis. In addition, cancer-associated endocrine cells are defined and characterized, thereby further broadening the composition of PDAC microenvironment.

Immune-related signature identifies IL1R2 as an immunological and prognostic biomarker in pancreatic cancer.

Objective: Pancreatic cancer is one of the most aggressive malignancies, a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making. Methods: A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature. Furthermore, the most pivotal gene in the signature was identified. The potential mechanism of the core gene function was revealed through GSEA, CIBERSORT, ESTIMATE, immunophenoscore (IPS) algorithm, single-cell analysis, and functional experiment. Results: An immune-related prognostic signature and associated nomogram were constructed and validated. Among the genes constituting the signature, interleukin 1 receptor type II (IL1R2) was identified as the gene occupying the most paramount position in the risk signature. Meanwhile, knockdown of IL1R2 significantly inhibited the proliferation, invasion, and migration ability of pancreatic cancer cells. Additionally, high IL1R2 expression was associated with reduced CD8+ T cell infiltration in pancreatic cancer microenvironment, which may be due to high programmed cell death-ligand-1 (PD-L1) expression in cancer cells. Finally, the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy. Conclusion: In conclusion, our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer, as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.

An applicability study of rapid artificial intelligence-assisted compressed sensing (ACS) in anal fistula magnetic resonance imaging.

Objective: To evaluate the applicability of artificial intelligence-assisted compressed sensing (ACS) to anal fistula magnetic resonance imaging (MRI). Methods: 51 patients were included in this study and underwent T2-weighted sequence of MRI examinations both with ACS and without ACS technology in a 3.0 T MR scanner. Subjective image quality scores, and objective image quality-related metrics including scanning time, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), were evaluated and statistically compared between the images collected with and without ACS. Results: No significant difference in the subjective image quality of lesion conspicuity was observed between the two groups. However, ACS MRI decreased the acquisition time with regard to control group (74.00 s vs. 156.00 s). Besides, SNR of perianal and muscle in the ACS group was significantly higher than that of the control group (164.07 ± 33.35 vs 130.81 ± 29.10, p < 0.001; 109.87 ± 22.01 vs 87.61 ± 17.95, p < 0.001; respectively). The CNR was significantly higher in the ACS group than in the control group (54.02 ± 23.98 vs 43.20 ± 21.00; p < 0.001). Moreover, the accuracy rate of the ACS groups in evaluating the direction and internal opening of the fistula was 88.89 %, exactly the same as that of the control group. Conclusion: We demonstrated the applicability of using ACS to accelerate MR of anal fistulas with improved SNR and CNR. Meanwhile, the accuracy rates of the ACS group and the control were equivalent in evaluating the direction and internal opening of the fistula, based on the results of surgical exploration.

Current Status and Health Risk Assessment of Heavy Metals Contamination in Tea across China.

Tea is a non-alcoholic beverage popular among Chinese people. However, due to the application of chemical and organic fertilizers in the tea planting process, the environment pollutionaround the tea plantation, and the instruments used in the processing, heavy metal elements will accumulate in the tea, which brings health risks for tea consumers. This study summarized heavy metal concentrations from 227 published papers and investigated the current contamination status of tea and tea plantation soils, and, finally, the risk of heavy metal exposure to tea consumers in China is assessed, in terms of both non-carcinogenic and carcinogenic risk. The average contamination of six heavy metals in tea-arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), and lead (Pb)-were 0.21, 0.14, 1.17, 14.6, 0.04, and 1.09 mg/kg, respectively. The areas with high concentrations of heavy metals in tea were concentrated primarily in southwest China, some areas in eastern China, and Shaanxi Province in northwest China. The non-carcinogenic risks of heavy metals in tea are all within safe limits. The national average HI value was 0.04, with the highest HI value of 0.18 in Tibet, which has the largest tea consumption in China. However, the carcinogenic risks of Cd in Shaanxi Province, Anhui Province, and southwest China exceed the acceptable range, and due attention should be given to these areas.

Downregulated APOD and FCGR2A correlates with immune infiltration and lipid-induced symptoms of irritable bowel syndrome.

Fat intake is among the most significant triggers for symptom development in patients with irritable bowel syndrome (IBS). Nevertheless, long-term restriction in fatty foods ingestion may lead to nutritional inadequacies. This study aimed to identify the crucial genes involved in lipid-induced gastrointestinal symptoms, contributing to helping IBS patients regulate fat. The clinical characteristics of the subjects were collected by questionnaire investigation and analyzed using multivariate logistic regression. Differentially expressed genes (DEG) and signaling pathways were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. ImmuInfiltration and CIBERSORT packages evaluated small intestine immune cell infiltration. Random forest and SVM-RFE algorithms were used to select hub genes. A receiver operating characteristic curve was used to access the diagnostic significance of each hub gene. Gene Set Enrichment Analysis (GSEA) was performed to identify hub genes' molecular processes in IBS development after lipid infusion. IBS patients' risk, severity, and quality of life increased with fat intake. In total, 116 robust DEGs were identified in IBS patients after lipid infusion using the GSE166869 dataset and were mainly clustered in the immune and inflammatory pathways. IBS patients had greater Neutrophils, CD4+ T cells, and M1 Macrophages than healthy controls. Furthermore, infiltration levels of Neutrophils and resting memory CD4+ T cells were inversely related to the expression of hub genes (IGKV1D-43, IGKV1-12, APOD, FCGR2A and IGKV2-29). After lipid infusion, GSEA results of each hub gene indicated the relevance of proinflammatory pathways in IBS pathogenesis. After verification, only APOD and FCGR2A were stably downregulated in small intestinal mucosa and plasma of IBS patients. The area under the curve of APOD combined with FCGR2A expression was 0.9. APOD and FCGR2A may be promising biomarkers for IBS diagnosis and lipid-sensitive IBS patients. Their potential roles in the immune microenvironment of the small intestinal mucosa may provide a vital clue to IBS precision therapy.

Single-breath-hold T2WI MRI with artificial intelligence-assisted technique in liver imaging: As compared with conventional respiratory-triggered T2WI.

OBJECTIVE: To investigate the clinical feasibility of single-breath-hold T2-weighted (SBH-T2WI) liver MRI using Artificial Intelligence-assisted Compressed Sensing (ACS) technique in liver imaging as compared with conventional respiratory-triggered T2WI (RT-T2WI). METHODS: From January 2021 to October 2021, 81 patients suspected of liver lesions were enrolled in this prospective study. The liver MRI was performed, including both RT-T2WI and ACS SBH-T2WI. Two experienced radiologists reviewed all images of each studied sequence, and recorded the lesion location and the largest diameter of the lesions. The image quality was quantitatively and qualitatively analyzed regarding signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contrast ratio (CR), motion artifact, lesion conspicuity, liver boundary sharpness, and overall image quality. The lesion detection and image quality were compared between two sequences using the Chi-square test or Wilcoxon signed-rank test. RESULTS: For lesion detection, 64 lesions were identified in 53 enrolled patients as the reference standard. The average size was 12.09 ± 7.4 mm for the benign lesions and 45.89 ± 22.01 mm for the malignant lesions. Of 64 liver lesions, ACS SBH-T2WI detected 60 lesions (93.8%), and RT-T2WI detected 58 lesions (90.6%). For image quality analysis, the motion artifact of ACS SBH-T2WI sequence was significantly reduced compared with the conventional RT-T2WI sequence (p < 0.05). The SNR, liver boundary sharpness, and overall image quality showed no statistical differences between the two sequences. While the CNR, CR, and lesion conspicuity of ACS SBH-T2WI were significantly better than RT-T2WI (all p < 0.05). CONCLUSIONS: The SBH-T2WI with ACS technique showed promising performance as it provided significantly better image quality and lesion detectability with a considerable decrease in scanning time as compared with the conventional RT-T2WI.

Effect of PVP Coating on LiMnBO3 Cathodes for Li-Ion Batteries.

LiMnBO3 is a potential cathode for Li-ion batteries, but it suffers from a low electrochemical activity. To improve the electrochemical performance of LiMnBO3, the effect of polyvinyl pyrrolidone (PVP) as carbon additive was studied. Monoclinic LiMnBO3/C and LiMnBO3-MnO/C materials were obtained by a solid-state method at 500 °C. The structure, morphology and electrochemical behavior of these materials are characterized and compared. The results show that carbon additives and ball-milling dispersants affect the formation of impurities in the final products, but MnO is beneficial for the performance of LiMnBO3. The sample of LiMnBO3-MnO/C delivered a high capacity of 162.1 mAh g-1 because the synergistic effect of the MnO/C composite and the suppression of the PVP coating on particle growth facilitates charge transfer and lithium-ion diffusion.

WITHDRAWN: Cardiac Troponin T: An Early Molecule Marker of Normalization of Left Ventricular Ejection Fraction in Patients with Peripartum Cardiomyopathy.

The article entitled, "Cardiac Troponin T: An Early Molecule Marker of Normalization of Left Ventricular Ejection Fraction in Patients with Peripartum Cardiomyopathy", by Li et al, which originally was published in this space, has been removed because an article by the same authors and reporting very similar work already has been published in HEART [Published Online First: 25 October 2006], entitled, "Troponin T measurement can predict persistent left ventricular dysfunction in peripartum cardiomyopathy", by Hu et al. The printed version of the article in HEART can be found at Heart 2007;93:488-490.

Effects of withdrawal of Xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with coronary artery disease.

OBJECTIVE: C-reactive protein (CRP) is considered a risk factor for coronary artery disease. In addition to its lipid-lowering properties, statin decreases the level of CRP. Abrupt cessation of statin therapy during treatment could increase CRP level independently of the elevation of serum lipids and the incidence of cardiac events in patients with atherosclerotic heart disease. Xuezhikang (XZK), an extract of cholestin, has a marked modulating effect on lipid and CRP concentrations in different study time course. However, no attention has been paid to the changes of lipid profile and CRP concentrations after withdrawal of XZK treatment. This study was designed to explore short-term time course effects on lipid profile and CRP concentrations after withdrawal of XZK treatment in coronary heart disease patients. MATERIALS AND METHODS: Seventy-five consecutive patients with documented coronary heart disease were randomly divided into three groups: 1. Pretreatment with XZK 1,200 mg daily for 6 weeks and then replaced by placebo (XZK discontinued group; n = 25); 2. Treatment with XZK 1,200 mg daily throughout the study (XZK continued group; n = 25); or 3. Placebo (no XZK group; n = 25). Lipid levels (total cholesterol, HDL-C, LDL-C and triglycerides) and CRP were assessed before receiving the XZK therapy, 1 day before discontinuation of XZK, and on days 1, 2, 3, 7 and 14 after discontinuation of XZK, respectively. RESULTS: After 6-week XZK treatment, the fasting total cholesterol, LDL-C, triglyceride and median hs-CRP concentrations decreased, whereas HDL-C concentration increased significantly (p < 0.001, respectively). At day 14 after discontinuation of XZK therapy, total cholesterol (15%), LDL-C (17%) and triglyceride (20%) significantly increased (p < 0.001, respectively), whereas HDL-C level (15%) significantly decreased (p < 0.05). The median level of CRP increased by 11, 65, 128, 103 and 101% on the first, second, third, seventh, and fourteenth day after withdrawal of XZK therapy (p > 0.05, <0.05, <0.001, <0.001, <0.001, compared with 1 day before withdrawal of XZK therapy, respectively). There was a prominent rebound of CRP concentration 3 days after discontinuation of XZK therapy. At this time point, hs-CRP concentration was higher than in the placebo group (p < 0.05). Seven to 14 days after discontinuation of XZK therapy, the hs-CRP concentration declined to a similar level as in the placebo group. No significant correlation was seen between the changes in hs-CRP and lipid profile at all time points. CONCLUSIONS: The level of hs-CRP increases on the second day after withdrawal of XZK and there is a prominent rebound 3 days after discontinuation of XZK therapy. The increase of CRP ends within 7 days, where lipids increase at 14 days after discontinuation of XZK therapy. The results may be clinically important for patients with coronary artery disease.