Surufatinib, a novel TKI targeting VEGFRs, FGFR1, and CSF1R, treats advanced neuroendocrine tumors but often causes diarrhea, which impairs patients’ health and anti-tumor efficacy. We’ve successfully established a rat model of surufatinib-induced diarrhea. This study aims to investigate Shengyang Qushi Decoction's mechanism in treating this diarrhea, focusing on intestinal mucosal barrier and inflammation, for clinical application. Sixty male rats were randomly assigned to five groups after a 3-day acclimation period: control, model, low-dose decoction (12g/kg), high-dose decoction (24g/kg), and positive control (Loperamide 0.36mg/kg) group. Except for the control group, all received oral administration of surufatinib at a dose of 110 mg/kg, followed by corresponding treatment after 12 hours. We monitored body weight, general condition and assessed diarrhea. Histological changes in the colon were evaluated. ELISA measured plasma diamine oxidase (DAO) and D-lactate levels, as well as serum inflammatory cytokines (TNF-α, IL-1β, IL-6). Western blotting assessed the expression of tight junction proteins, inflammatory cytokines (TNF-α, IL-1β), and key proteins in the NF-κB pathway (IKK-α, IκB-α, NF-κB p65) in colon tissue. Rats in the high-dose decoction group had slower weight gain than the control but more than other groups, with improved physical appearance and activity levels, and food and water intake similar to the control. Diarrhea rates were 50%, 17%, and 42% in the low-dose decoction, high-dose decoction, and positive control groups, respectively. Hematoxylin-eosin staining revealed intact colonic structure in the control group with orderly mucosal epithelia and no abnormalities. In the high-dose decoction group showed intact colon mucosa with minimal inflammation and no congestion or edema. DAO levels were not significantly different among groups, but D-lactate levels were significantly higher in the model group (P < 0.01), and decreased after intervention, most notably in the high-dose decoction group. After drug intervention, the colonic tight junction proteins increased, most notably in the high-dose decoction group (P < 0.01 vs. model). Serum TNF-α, IL-1β, and IL-6 levels declined, with the high-dose decoction group showing the greatest reduction (P < 0.01). And the colon’s TNF-α and IL-1β proteins followed the same trend (P < 0.01). Western blotting showed reduced expression of phosphorylated NF-κB pathway proteins (p-IKK-α, p-IκB-α, p-p65) after intervention, with the high-dose decoction group showing the greatest decrease (P < 0.01). Animal experiments confirm Shengyang Qushi Decoction's efficacy in treating surufatinib-induced diarrhea. It mitigates colonic tight junction damage, reduces mucosal permeability, inhibits NF-κB signaling pathway activation, and alleviates colonic inflammation. Huangying Tan, Shaobo Hu. Efficacy and mechanistic insights of Shengyang Qushi Decoction in managing surufatinib-associated diarrhea [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1043.

BACKGROUND Autoimmune gastritis (AIG) is frequently associated with one or more comorbid conditions, among which type I gastric neuroendocrine tumors (gNETs) warrant significant clinical concern. However, risk factors for the development of gNETs in AIG populations remain poorly defined. AIM To characterize the clinical and endoscopic profiles of AIG and identify potential risk factors for gNETs development. METHODS In this single-center cross-sectional study carried out at a tertiary hospital, 303 patients with AIG over an 8-year period were retrospectively categorized into gNETs (n = 116) and non-gNETs (n = 187) groups. Endoscopic and clinical parameters were analyzed. Endoscopic features were systematically reevaluated according to the 2023 Japanese diagnostic criteria for AIG. Feature selection was performed using the Boruta algorithm, and the model discriminative ability was evaluated via receiver operating characteristic curve analysis. RESULTS Among the 303 patients with AIG, 116 had gNETs and 187 did not. Compared with the non-gNETs group, patients in the gNETs group were younger (54.3 years vs 60.6 years, P < 0.001), had higher rate of vitamin B12 deficiency (77.2% vs 55.8%, P < 0.001), lower pepsinogen I (4.3 ng/mL vs 7.4 ng/mL, P < 0.001) and pepsinogen I/II ratios (0.7 vs. 1.1, P < 0.001), and lower prior Helicobacter pylori infection rate (3.4% vs 21.4%, P < 0.001). Endoscopically, the gNETs group showed a lower incidence of oxyntic mucosal remnants, hyperplastic polyps, and patchy antral redness. The predictive model incorporating age, prior Helicobacter pylori infection, vitamin B12 level, gastric hyperplastic polyps, and patchy antral redness showed an area under the curve of 0.830. CONCLUSION Patients with AIG or gNETs exhibit specific clinical and endoscopic features. The predictive model demonstrated favorable discriminative ability and may facilitate risk stratification of gNETs in patients with AIG.

Construction of the sensitive label-free ECL immunosensor BSA/anti-CgB/GDY QDs@Au NPs/GCE and its application for the detection of the pNET marker chromogranin B.

Using (27.12 +/- 0.14) x 10(8) psi(3686) decays and data samples of e(+)e(-) collisions with root s from 4.130 to 4.780 GeV collected with the BESIII detector, we report the first observation of the electromagnetic Dalitz transition h(c) -> e(+)e(-)eta(c) with a statistical significance of 5.4 sigma. We measure the ratio of the branching fractions B(h(c) -> e(+)e(-)eta(c))/B(h(c) -> gamma eta(c)) separately for the h(c) samples produced via psi(3686) -> pi(0)h(c) and e(+)e(-) -> pi(+)pi(-)h(c). The average ratio is determined to be (0.59 +/- 0.10(stat) +/- 0.04(syst))%, where the uncertainty includes both statistical and systematic components.

Background: Thymic neuroendocrine tumors (Th-NETs) are rare and aggressive, with a scarcity of research on predicting patient prognosis. Our study aimed to assess the impact of prognostic markers and temozolomide (TMZ)-based chemotherapy on survival in Th-NETs. Methods: We retrospectively reviewed the medical records of patients diagnosed with Th-NETs between 2013 and 2023 at our institution. We collected clinicopathological data, including tumor pathological grading, staging, serum concentrations of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide, levels of inflammatory factors, and expression of oxygen 6-methylguanine-DNA methyltransferase (MGMT). Treatment details (such as surgery and chemotherapy) and survival outcomes were also documented. Results: A total of 32 patients were included in our study after excluding those without complete available information. The median progression-free survival (PFS) was 12.5 months (95%CI, 8–16 months) for 19 patients who received TMZ-based chemotherapy. Twenty-one patients underwent surgery as the primary treatment, demonstrating a median disease-free survival (DFS) of 51.0 months. The inflammatory factor neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic indicator of DFS in postoperative patients and PFS in TMZ-treated patients. The overall 3-, 5-, and 10-year survival rates were 86.6%, 69.5%, and 33.8%, respectively. Ki67 level exceeding 10% (p = 0.048) and absence of surgical resection (p = 0.003) were significantly associated with worse overall survival (OS). Conclusion: Surgical treatment was currently the primary method for treating Th-NETs, and postoperative adjuvant therapy was an essential consideration for specific patient cohorts. Despite widespread positive MGMT expression, TMZ-based chemotherapy showed promise. Some potential prognostic biomarkers such as NLR and NSE need more attention.

Hematological indicators of chronic systemic inflammation are significant biomarkers for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). We performed a systematic review and meta-analysis to assess the impact of certain factors on the overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of patients with GEP-NENs. These factors include the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and C-reactive protein (CRP) levels. After searching the Medline, Embase, and Cochrane Library databases from January 1, 2000 to October 20, 2022 and the American Society of Clinical Oncology conference proceedings from January 1, 2017, hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted. Subgroup analyses were conducted to identify the origins of heterogeneity and examine the impact of factor grouping. The effects of the cut-off values and sample size were assessed by meta-regression. The results revealed that higher NLRs, PLRs, and CRP levels were associated with shorter OS (HR = 2.09, 95% CI = 1.55-2.8; HR = 1.79, 95% CI = 1.40-2.28; and HR = 2.88, 95% CI = 2.09-3.95, respectively; all p < 0.001). Higher NLRs and lower LMRs were associated with shorter DFS (HR = 3.34, 95% CI = 2.11-5.29 and HR = 2.71, 95% CI = 2.27-3.24, respectively; both p < 0.001). Higher PLRs and CRP levels were correlated with shorter PFS (HR = 3.48, 95% CI = 1.34-9.03, p = 0.01 and HR = 3.14, 95% CI = 1.63-6.08, p = 0.001). As demonstrated in the research, hematological indicators of systemic inflammation are promising biomarkers for GEP-NEN assessment.

Background:Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a rare group of diseases with poor prognosis and the assessment of its prognosis is a significant challenge. This study aimed to develop and validate a prognostic nomogram to assess overall survival (OS) in patients with GEP-NEC. Methods:Patients diagnosed with poorly differentiated GEP-NEC were collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2015 and were randomly assigned to the training or validation cohort in a 7:3 ratio. The data included details of clinicopathological characteristics, therapeutic interventions and survival outcomes. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Nomogram was used to predict OS at 1 and 2 years. The nomogram was internally validated with validation cohort, and its predictive ability was evaluated using concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and integrated discrimination improvement (IDI) index. Results:A total of 887 patients were divided into the training group (n=623) and the validation group (n=264). A total of 476 patients (53.66%) were in stage IV. Based on multivariate analysis, a nomogram was constructed with age, gender, N stage, tumor size, primary tumor resection, radiotherapy and chemotherapy (P<0.05). The C-index was 0.701 [95% confidential interval (CI): 0.677-0.725] and 0.731 (95% CI: 0.698-0.764) for the training and validation groups, respectively. The C-index, ROC, IDI and DCA results indicated that this nomogram model has a good predictive value. Conclusions:In this study, a nomogram model based on seven independent prognostic factors provided visualization of the risk and could help clinicians predict the 1-year and 2-year OS for GEP-NEC. This tool can provide personalized survival predictions and improve clinical decision making for the management of GEP-NEC.

Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing’s syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients’ circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.

Neuroendocrine neoplasms (NENs) are a group of rare tumors with strong heterogeneity. Among these tumors, well‐differentiated tumors can have a relatively good survival prognosis, while some tumors can have strong malignant potential and lead to increased mortality. Traditional Chinese medicine (TCM), which has a long history of thousands of years, has been widely used to treat tumors due to its unique advantages, such as economy, efficacy and few side effects. In recent years, the role of TCM in the treatment of NENs has gradually emerged. It can not only help prevent tumor recurrence and reduce the side effects of radiotherapy and chemotherapy but also relieve symptoms and improve quality of life. Various clinical studies have indicated that TCM has achieved good curative effects at different stages of treatment. We summarized the last 10 years of research progress on the clinical application of TCM in the treatment of NENs from four points of entry, aiming to provide a reference for the treatment of NENs.

目的 基于数据挖掘探讨国家专利数据库的中药复方治疗胰腺癌的用药规律.方法 通过中国专利公布公告网站检索建库至2022年5月治疗胰腺癌的中药复方专利,使用Excel软件建立复方数据库,运用古今医案云平台、IBM SPSS Modeler及IBM SPSS Statistics软件将规范后的数据进行用药规律分析.结果 共纳入治疗胰腺癌的中药复方专利55项,包含中药426味.药性以寒、温为主;药味以苦、甘、辛为主;归经以肝、脾、肺为主;高频单味药有白花蛇舌草、甘草、白术、延胡索、半枝莲、当归、薏苡仁、柴胡等.常用药对是白术-甘草、白花蛇舌草-半枝莲等;关联分析获得药物组合27个;高频药物聚类分析获得3个核心药物组合.结论 中药复方专利治疗胰腺癌有规律可循,组方寒温并用,调和肝脾,以扶正固本,解毒抑瘤为基本治法.

Cross sections for the process ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}_{S}^{0}{K}_{S}^{0}J/\ensuremath{\psi}$ at center-of-mass energies from 4.128 to 4.950 GeV are measured using data samples with a total integrated luminosity of $21.2\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ collected by the BESIII detector operating at the BEPCII storage ring. The $Y(4230)$ state is observed in the energy dependence of the ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}_{S}^{0}{K}_{S}^{0}J/\ensuremath{\psi}$ cross section for the first time with a statistical significance of $26.0\ensuremath{\sigma}$. In addition, an enhancement around 4.710 GeV, labeled as the $Y(4710)$, is seen with a statistical significance of $4.2\ensuremath{\sigma}$. There is no clear structure around 4.484 GeV. Using a fit with a coherent sum of three Breit-Wigner functions, we determine the mass and width of the $Y(4230)$ state to be $4226.9\ifmmode\pm\else\textpm\fi{}6.6\ifmmode\pm\else\textpm\fi{}22.0\text{ }\text{ }\mathrm{MeV}/{c}^{2}$ and $71.7\ifmmode\pm\else\textpm\fi{}16.2\ifmmode\pm\else\textpm\fi{}32.8\text{ }\text{ }\mathrm{MeV}$, respectively, and the mass and width of the $Y(4710)$ state to be $4704.0\ifmmode\pm\else\textpm\fi{}52.3\ifmmode\pm\else\textpm\fi{}69.5\text{ }\text{ }\mathrm{MeV}/{c}^{2}$ and $183.2\ifmmode\pm\else\textpm\fi{}114.0\ifmmode\pm\else\textpm\fi{}96.1\text{ }\text{ }\mathrm{MeV}$, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the average Born cross section ratio $\frac{{\ensuremath{\sigma}}^{\text{Born}}({e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}_{S}^{0}{K}_{S}^{0}J/\ensuremath{\psi})}{{\ensuremath{\sigma}}^{\text{Born}}({e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}^{+}{K}^{\ensuremath{-}}J/\ensuremath{\psi})}$ is measured to be ${0.388}_{\ensuremath{-}0.028}^{+0.035}\ifmmode\pm\else\textpm\fi{}0.016$, or ${0.426}_{\ensuremath{-}0.031}^{+0.038}\ifmmode\pm\else\textpm\fi{}0.018$ if three-body phase space is considered.

Gamma rays from HESS J1849−000, a middle-aged TeV pulsar wind nebula (PWN), are observed by the Tibet air shower array and the muon detector array. The detection significance of gamma rays reaches 4.0 σ and 4.4 σ levels above 25 TeV and 100 TeV, respectively, in units of the Gaussian standard deviation σ . The energy spectrum measured between 40 TeV < E < 320 TeV for the first time is described with a simple power-law function of dN / dE = ( 2.86 ± 1.44 ) × 10 − 16 ( E / 40 TeV ) − 2.24 ± 0.41 TeV − 1 cm − 2 s − 1 . The gamma-ray energy spectrum from the sub-TeV ( E < 1 TeV) to sub-PeV (100 TeV < E < 1 PeV) ranges, including the results of previous studies, can be modeled with the leptonic scenario, i.e., inverse Compton scattering by high-energy electrons accelerated by the PWN of PSR J1849−0001. On the other hand, the gamma-ray energy spectrum can also be modeled with the hadronic scenario in which gamma rays are generated from the decay of neutral pions produced by collisions between accelerated cosmic-ray protons and the ambient molecular cloud found in the gamma-ray-emitting region. The cutoff energy of cosmic-ray protons E p,cut is estimated as log 10 ( E p , cut / TeV ) = 3.73 − 0.66 + 2.98 , suggesting that protons are accelerated up to the PeV energy range. Our study thus proposes that HESS J1849−000 should be further investigated as a new candidate as a Galactic PeV cosmic-ray accelerator, or “PeVatron.”

We present a measurement of the dressed cross sections for e+e- -> phi eta at different center-of-mass energies between 3.508 and 4.600 GeV based on 15.1 fb-1 of e+e- annihilation data collected with the BESIII detector operating at the BEPCII collider. In addition, a search for the decay Y(4230) -> phi eta is performed. No clear signal is observed and the corresponding upper limit is provided.

The genetic characteristics of rectal neuroendocrine tumors (R-NETs) were poorly understood. Depicting the genetic characteristics may provide a biological basis for prognosis prediction and novel treatment development. Tissues of 18 R-NET patients were analyzed using whole-exome sequencing. The median tumor mutation burden (TMB) and microsatellite instability (MSI) were 1.15 Muts/MB (range, 0.03-23.28) and 0.36 (range, 0.00-10.97), respectively. Genes involved in P53 signaling, PI3K-AKT signaling, DNA damage repair, WNT signaling, etc. were frequently altered. Higher TMB (P = 0.078), higher CNV (P = 0.110), somatic mutation of CCDC168 (P = 0.049), HMCN1 (P = 0.040), MYO10 (P = 0.007), and amplification of ZC3H13 (P < 0.001) were associated with shorter OS. Potentially targetable gene alterations (PTGAs) were seen in 72% of the patients. FGFR1 amplification (22%) was the most common PTGA followed by BARD1 and BRCA2 mutation (each 17%). As for gene variations associated with the efficacy of immune checkpoint blockade (ICB), FAT1 alteration (39%) and PTEN depletion (28%) were commonly observed. In conclusion, frequently altered oncogenic pathways might contribute to the development and progression of R-NETs. Gene alterations significantly associated with prognosis might be potential novel targets. Targeted therapy might be a promising strategy as targetable alterations were prevalent in R-NETs. FAT1 alteration and PTEN depletion might be the main genetic alterations influencing the response to ICB besides overall low TMB and MSI in R-NETs.