Serum Lipid Level in Evaluating Chinese Pancreatic Neuroendocrine Neoplasms: A Retrospective Study.

BACKGROUND: Pancreatic neuroendocrine neoplasms (p-NENs) are relatively rare and highly heterogeneous. Dyslipidemia may be related to the risk of developing p-NENs, although dyslipidemia in patients with p-NENs is rarely reported. In this study, the clinical characteristics of p-NENs patients with different lipid levels and their prognostic value in p-NENs patients were evaluated. METHODS: Patients (n=211) with p-NENs hospitalized at Jiangsu Neuroendocrine Tumor Centre of Jiangsu Province Hospital from December 2018 to December 2022 were enrolled. Clinical data related to p-NENs were collected. Based on the EGA database, the related lipoprotein, low-density lipoprotein receptor (LDLR) and high-density lipoprotein binding protein (HDLBP) mRNA in p-NENs and paratumoral tissues and the follow-up information of p-NENs were evaluated. RESULTS: A total of 175 p-NENs patients ultimately met the inclusion criteria. The ki67 index was higher in p-NENs patients with elevated lipid with the proportion of≥5, and in those with AJCC stage III and stage IV than p-NENs patients with low-level lipid. In p-NENs patients, the expression of HDLBP mRNA was downregulated in p-NENs tissues compared to the paratumoral tissues. Survival analysis showed that serum lipids had no effect on the prognosis of p-NENs; however, high LDLR level p-NENs were at the risk of poor survival. CONCLUSION: Serum lipid level in p-NENs can affect the grading and staging, but the correlation with the prognosis of p-NENs is not significant. However, dyslipidemia may be a potential predictor of p-NENs.

ROS-responsive ADPH nanoparticles for image-guided surgery.

In recent years, organic fluorescent probes with tumor microenvironment (TME)-responsive fluorescence turn-on properties have been increasingly used in imaging-guided tumor resection due to their higher signal-to-noise ratio for tumor imaging compared to non-responsive fluorescent probes. However, although researchers have developed many organic fluorescent nanoprobes responsive to pH, GSH, and other TME, few probes that respond to high levels of reactive oxygen species (ROS) in the TME have been reported in imaging-guided surgery applications. In this work, we prepared Amplex® Red (ADHP) with excellent ROS response performance as an ROS-responsive nanoprobe and studied its application in image-guided tumor resection for the first time. To confirm whether the nanoprobe can be used as an effective biological indicator to distinguish tumor sites, we first detected 4T1 cells with the ADHP nanoprobe, demonstrating that the probe can utilize ROS in tumor cells for responsive real-time imaging. Furthermore, we conducted fluorescence imaging in vivo in 4T1 tumor-bearing mice, and the ADHP probe can rapidly oxidize to form resorufin in response to ROS, which can effectively reduce the background fluorescence signal compared with the single resorufin probe. Finally, we successfully carried out image-guided surgery of 4T1 abdominal tumors under the guidance of fluorescence signals. This work provides a new idea for developing more TME-responsive fluorescent probes and exploring their application in image-guided surgery.

Diagnosis and treatment of a small intestinal neuroendocrine neoplasm by double balloon enteroscopy combined with laparoscopy: a case report

We report the case of a jejunum neuroendocrine neoplasm with liver metastases, the lesion showed somatostatin receptor expression in the junction of duodenum and jejunum without enlarged lymph nodes in 68Ga-DOTA-NOC PET/CT scan, definitive diagnosis and treatment depend on double-balloon enteroscopy and laparoscopy. This is a meaningful and thought-provoking process. (AU)

In Situ Growth of Strained Matrix on CsPbI3 Perovskite Quantum Dots for Balanced Conductivity and Stability.

Their nanoscale size endows perovskite quantum dots (QDs) with processing flexibility and high tunability of optoelectronic properties. The vast surface area also provides an opportunity for ligand engineering to offer QDs extra protection, which however, will impede charge transport in the QD array. Currently, the surface treatments that can balance both stability and conductivity of the perovskite QD array remain a huge challenge. Here, we report in situ growth of an atomic guanidinium lead iodide perovskite matrix on CsPbI3 QDs. In addition to the effect of trap passivation, the matrix can also provide substantial surface strain to improve the QD phase stability. Meanwhile, the ultrathin matrix allows efficient coupling and charge transport in the QD solids. As a result, the CsPbI3 QD solar cells can achieve both superior device stability and performance. We believe the development of a multifunctional surface matrix will become one of the future research focuses in perovskite QD-based devices.

Diagnosis and treatment of a small intestinal neuroendocrine neoplasm by double balloon enteroscopy combined with laparoscopy: a case report.

We report the case of a jejunum neuroendocrine neoplasm with liver metastases, the lesion showed somatostatin receptor expression in the junction of duodenum and jejunum without enlarged lymph nodes in 68Ga-DOTA-NOC PET/CT scan, definitive diagnosis and treatment depend on double-balloon enteroscopy and laparoscopy. This is a meaningful and thought-provoking process.

Cation-Doping in Organic-Inorganic Perovskites to Improve the Structural Stability from Theoretical Prediction.

With outstanding photoelectric properties, organic-inorganic perovskites have become promising materials in the application of solar cells. However, their low stability limits their high conversion efficiency. On the basis of first-principles calculations, we screened out the optimal dopant into MAPbI3 from a variety of organic cations, and further revealed the mechanism underneath for the improved stability of cations doping. Our results have demonstrated that the doping of large-size cations (i.e., IPA+, TriMA+, and GA+) could efficiently inhibit the formation and diffusion of structural defects with high defect formation energies and large migration barriers, which is associated with the lattice expansion and greater hydrogen-bond formation. Our theoretical findings address crucial guidelines to design and synthesize the organic-inorganic perovskite materials with high stability, and provide valuable insights in understanding the stability mechanism, which may enhance the photovoltaic efficiency of perovskite materials and extend their wide applications.

Development and validation of prognostic nomograms for patients with colon neuroendocrine neoplasms.

BACKGROUND: Colon neuroendocrine neoplasms (NENs) have one of the poorest median overall survival (OS) rates among all NENs. The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system-currently the most commonly used prediction model-has limited prediction accuracy because it does not include parameters such as age, sex, and treatment. The aim of this study was to construct nomograms containing various clinically important parameters to predict the prognosis of patients with colon NENs more accurately. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a retrospective analysis of colon NENs diagnosed from 1975 to 2016. Data were collected from 1196 patients; almost half were female (617/1196, 51.6%), and the average age was 61.94 ± 13.05 years. Based on the age triple cut-off values, there were 396 (33.1%), 408 (34.1%), and 392 (32.8%) patients in age groups 0-55 years, 55-67 years, and ≥ 68 years, respectively. Patients were randomized into training and validation cohorts (3:1). Independent prognostic factors were used for construction of nomograms to precisely predict OS and cancer-specific survival (CSS) in patients with colon NENs. RESULTS: Multivariate analysis showed that age ≥ 68 years, sex, tumor size, grade, chemotherapy, N stage, and M stage were independent predictors of OS. In the validation cohort, the Concordance index (C-index) values of the OS and CSS nomograms were 0.8345 (95% confidence interval [CI], 0.8044-0.8646) and 0.8209 (95% CI, 0.7808-0.861), respectively. C-index also indicated superior performance of both nomograms (C-index 0.8347 for OS and 0.8668 for CSS) compared with the AJCC TNM classification (C-index 0.7159 for OS and 0.7366 for CSS). CONCLUSIONS: We established and validated new nomograms for more precise prediction of OS and CSS in patients with colon NENs to facilitate individualized clinical decisions.

Octreotide-Conjugated Core-Cross-Linked Micelles with pH/Redox Responsivity Loaded with Etoposide for Neuroendocrine Neoplasms Therapy and Bioimaging with Photoquenching Resistance.

The study of multifunctional polymer micelles combined with chemotherapy due to reduced systemic toxicity and enhanced efficacy has attracted intensive attention. Herein, a multifunctional core-cross-linked hybrid micelle system based on mPEG- b-PGu(BA-TPE) and OCT-PEG- b-PGu(DA-TPE) with pH- and redox-triggered drug release and aggregation-induced emission (AIE) active imaging has been developed for active targeting of neuroendocrine neoplasms (NENs), especially neuroendocrine carcinomas (NECs) with poor prognosis. These micelles showed excellent biocompatibility and stability. After the formation of borate ester bonds, core-cross-linked micelles (CCLMs) showed enhanced emission properties. In addition, etoposide (ETO), one of the most important anticancer drugs of NECs, was loaded into the hydrophobic core of micelles by self-assembly with an average diameter of 274.6 nm and spherical morphology. Octreotide (OCT) conjugated onto the micelles enhanced cellular uptake by receptor-mediated endocytosis. ETO-loaded micelles demonstrated the dual-responsive triggered intracellular drug release and great tumor suppression ability in vitro. Compared with free ETO, ETO-loaded CCLMs exhibited a considerable antitumor effect and significantly reduced side effects. Considering the active tumor targeting, dual-responsive drug release and the AIE effect, the polymer micelle system will be a potential candidate for diagnosis and oncotherapy of NENs.

DNA Methylation of miR-122 Aggravates Oxidative Stress in Colitis Targeting SELENBP1 Partially by p65NF-κB Signaling.

Aberrant microRNA (miRNA) expressions contribute to the development and progression of various diseases, including Crohn's disease (CD). However, the accurate mechanisms of miRNAs in CD are definitely unclear. We employed colonic tissue samples from normal volunteers and CD patients, an acute mice colitis model induced by 2,4,6-trinitro-benzene-sulfonic acid (TNBS), and a cellular oxidative stress model induced by H2O2 in HT-29 cells to determine the effects of oxidative stress on expressions of miR-122, selenium-binding protein 1 (SELENBP1, SBP1), p65 nuclear factor κB (p65NF-κB) signaling, and DNA methylation. We found that SBP1 was mainly located on epithelial cells and was significantly increased in patients with active CD. SBP1 was the target gene of miR-122. miR-122 expression was downregulated while SBP1 expression was upregulated under TNBS-induced colitis or oxidative stress. Pre-miR-122 or siRNA SBP1 (si-SBP1) treatment ameliorated acute TNBS-induced colitis and H2O2-induced oxidative stress. Cotreatment of pre-miR-122 and si-SBP1 enhanced these effects. Besides, pre-miR-122 and si-SBP1 obviously activated the p65NF-κB signaling by phosphorylation of IκBα. Bisulfite sequencing of the CpG islands in the promoter region of miR-122 showed that CpG methylation was significantly increased under oxidative stress. Treating cells with 5'-AZA which was well known as a DNA-demethylating agent significantly increased miR-122 expression. Our results suggest that oxidative stress-induced DNA methylation of miR-122 aggravates colitis targeting SELENBP1 partially by p65NF-κB signaling and may promote the progression of CD.