Osteosarcoma (OS) represents one of the most prevalent primary malignant bone tumors affecting children and adolescents. Despite the establishment of standard treatment protocols (surgery and chemotherapy) in the 1980s, patient survival rates remain suboptimal. This underscores the critical need for the development and investigation of novel therapeutic technologies. Neutron capture therapy (NCT), an emerging precision therapeutic modality, selectively targets and eradicates tumor cells while minimizing damage to surrounding healthy tissues. In this study, we developed a novel agent, Gd-DOTA-BMTP, by attaching the cyclic nonapeptide c(CGRRAGGSC) to DOTA, followed by chelation of gadolinium (Gd) to the DOTA-BMTP. This peptide can specifically targeting osteosarcoma and binding to IL-11Rα, a cell surface receptor. Gd-DOTA-BMTP demonstrated excellent targeting specificity and a favorable biosafety profile. Furthermore, rigorous in vitro and in vivo evaluations confirmed the efficacy of Gd-DOTA-BMTP in suppressing osteosarcoma, specifically by enhancing radiosensitivity to neutron irradiation. Collectively, these findings suggest that Gd-DOTA-BMTP holds potential as a candidate for Gadolinium Neutron Capture Therapy (Gd-NCT) of osteosarcoma. An overview of the process of neutron capture therapy mediated by Gd-DOTA-BMTP

The dynamic characteristics of gut microbiome and metabolome during radiopharmaceutical therapy and their correlation with treatment response have not been well clarified. Herein, we conducted a prospective longitudinal study on papillary thyroid carcinoma patients receiving initial radioactive iodine (RAI) treatment. Three fecal samples from each patient were sequentially collected at the day before (Day0), 3 days upon (Day3), and 30 days upon (Day30) receiving RAI (totally 75 samples) for 16S rRNA amplicon sequencing and metabolome profiling. The results revealed transient fluctuations of gut microbiota and metabolites during RAI treatment, as shown by probiotic Blautia and anti-inflammatory and antioxidant metabolites first decreased on Day3 and then increased on Day30, while the opposite trends of opportunistic pathogens Streptococcus were observed. Meanwhile, correlation analysis showed a complex interplay between the temporal alterations of Blautia and the anti-inflammatory and antioxidant metabolites. Furthermore, the variability of intestinal flora and metabolites at multiple time points corresponded to the response to RAI treatment. In conclusion, our findings indicated that internal irradiation could lead to transient fluctuations of gut microbiota and metabolites, suggesting that probiotics might be beneficial for patients receiving RAI. Additionally, we provided a new perspective to screen for noninvasive biomarkers corresponding to the response to RAI treatment. IMPORTANCE:This study provides the first longitudinal profiling demonstrating that radioactive iodine (RAI) therapy induces transient yet dynamic fluctuations in both the gut microbiome and metabolome. Key beneficial bacteria and anti-inflammatory metabolites were significantly reduced immediately after treatment, followed by a recovery trend. Moreover, patients with different treatment responses showed diverse microbial and metabolic profiles. These findings highlight the potential for probiotic based interventions to maintain gut ecological homeostasis and suggest novel non invasive microbial biomarkers for predicting RAI efficacy.This study is registered with ClinicalTrials.gov as ChiCTR2100053810.

BACKGROUND:Pharyngeal squamous cell carcinoma (PSCC) is an aggressive subtype of head and neck squamous cell carcinoma (HNSCC) with poor prognosis and low survival rates. Immune checkpoint inhibitors (ICIs) show promise, but less than 20% of HNSCC patients respond positively. Targeted radionuclide therapy (TRT) combines radionuclides with monoclonal antibodies to target tumor cells. This study created a reliable animal model of PSCC for evaluating the therapeutic efficacy of 131I-aPD-L1. METHODS:Nude mice were subcutaneously implanted with FaDu cells-a human PSCC cell line characterized by high PD-L1 expression. The synthesis of 131I-aPD-L1 was optimized by varying labeling conditions, achieving a labeling efficiency of over 90%. Mice were divided into experimental and control groups; the experimental group received a single intravenous injection of 500 μCi 131I-aPD-L1. Accumulation of 131I-aPD-L1 in tumor tissues was confirmed by animal single-photon emission computed tomography (SPECT). Tumor volume and mouse body weight were measured every 3 days for 30 days. At the end of the study, tumor tissues were stained for histological examination and immunohistochemical analysis of Bcl-2 and Caspase-3 expression levels. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was also performed on tumor tissues. RESULTS:SPECT verified a significant accumulation of 131I in FaDu tumor tissue. The experimental group exhibited significantly slower tumor volume increase compared to the control group (t = 2.37, p < 0.05). Additionally, a significant reduction in body weight was observed in the 131I-aPD-L1 group compared to the control group (t = 5.624, p < 0.01). HE staining showed extensive tumor necrosis in the experimental group. Immunohistochemical analysis revealed negative Bcl-2 expression and higher caspase-3 expression in the experimental group, indicating enhanced apoptosis and necrosis in tumor cells. Furthermore, TUNEL assay further confirmed that 131I exerted cytotoxic effects by inducing DNA fragmentation. CONCLUSIONS:Collectively, our findings demonstrate the promising therapeutic potential of 131I-aPD-L1 for PSCC, particularly in patients with drug resistance or recurrent head and neck tumors. However, the use of nude mice may have impacted the full therapeutic efficacy and synergistic potential observed with immunotherapy. Future studies should utilize immunocompetent models to better assess the probe's therapeutic impact and to explore its synergistic effects with immunotherapy and reduce the dose of 131I to mitigate its toxic effects.

Gadolinium-neutron capture therapy (Gd-NCT) employs isotopically enriched Gadolinium (Gd) and thermal neutrons to selectively target cancer cells. This study investigated the targeting efficacy of 157Gd-DOTA-PSMA (Prostate-Specific Membrane Antigen) in prostate cancer and explored its potential applications in Gd-NCT. We developed 157Gd-DOTA-PSMA, a novel theranostic bio-gadolinium agent specifically designed for magnetic resonance imaging (MRI)-guided Gd-NCT. 68 Ga-DOTA-PSMA positron emission tomography-computed tomography (PET/CT) imaging showed peak radiotracer uptake at 2 h post-injection, with a tumor-to-non-tumor (T/NT) ratio of 6.95 ± 0.60. MRI analysis confirmed a stable T1 signal enhancement 2 h post-injection. Time-of-flight inductively coupled plasma mass spectrometry (TOF-ICP-MS) revealed significantly elevated Gd concentrations in 22Rv1 tumor compared to PC-3 tumor and other healthy organs. ICP-MS analysis showed Gd concentrations of 165.69 μg [Gd]/g in 22Rv1 tumors and 35.25 μg [Gd]/g in blood, yielding a tumor-to-blood (T/B) ratio of 4.65 ± 0.54 and a T/NT ratio of 3.65 ± 0.49. Neutron irradiation with 157Gd-DOTA-PSMA reduced cell viability, inhibited colony formation, and induced DNA damage and apoptosis in 22Rv1 cells. In 22Rv1 mice, γ-H2AX levels peaked at 6 h post-irradiation, accompanied by an increase in pro-apoptotic proteins and a decrease in anti-apoptotic proteins over 24 h. In the NCT group following the injection of 157Gd-DOTA-PSMA, there was effective suppression of tumor growth without a loss of body weight, resulting in a 1.7-fold increase in median survival compared to control group. 157Gd-DOTA-PSMA, as a theranostic bio-gadolinium agent designed for targeted Gd-NCT in prostate cancer, represents a novel therapeutic approach and broadens the scope of potential applications of neutron capture therapy.

Gadolinium-neutron capture therapy (Gd-NCT) employs Gadolinium (Gd) isotopes and thermal neutrons to specifically target and kill cancer at cells level. This study investigates the targeting efficacy of 157Gd-DOTA-HK (DHK), a novel agent designed for Gd-NCT and MRI. We synthesized 157Gd-DHK, which combines a Gd-DOTA complex as a neutron capturer and MRI probe with αvβ6 binding peptide (HK) for targeted Pancreas adenocarcinoma (PDAC) therapy. 157Gd-DHK demonstrated a significantly high binding affinity for BxPC-3 cells. scintigraphy revealed that the optimal time window for Gd-NCT was 26 h after injection. The conjugate’s imaging capabilities and its potential as an MRI contrast agent were validated. The conjugate effectively triggered nuclear reactions via Gd-NCT, leading to efficient tumor cell destruction. Photon sensitization studies showed that 157Gd-DHK induced photon-mediated phototoxicity in cancer cells while exhibiting minimal toxicity. 157Gd-DHK shows great potential as a theranostic agent for targeted imaging of PDAC and Gd-NCT applications. It presents a novel strategy to enhance the specificity and efficacy of Gd-NCT in cancer treatment.

Abstract Inflammation is a core mechanism for oncogenesis. Chemokines act as important inflammation mediators in chronic inflammation and the tumor inflammatory response. However, limited information is known about chemokines in hepatocellular carcinoma (HCC), a disease that is almost entirely derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. This protumor feature was confirmed in clinical samples of human HCC. CXCL1 enhances tumorigenesis in the hepatic inflammatory microenvironment directly through tumor cells and indirectly through recruitment of macrophages. Increasing the number of macrophages in the tumor microenvironment (TME) promoted tumor cell Epithelial-mesenchymal transition (EMT) capacity and significantly elevated CXCL1 levels in the TME partly through NF-κB/IL-1𝛽 activation. To investigate the potential therapeutic value of CXCL1 in HCC with inflammatory background, blocking CXCL1 and blocking CXCL1 combined with the chemotherapy agent doxorubicin (DOX), which aimes to reshape the TME, were administered. It has been shown that blocking CXCL1-CXCR2 inhibits tumor progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to have a synchronous effect in HCC by reducing pro-tumor macrophages in the TME and suppressing tumor cell progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.

Inflammation is a core mechanism for oncogenesis. Chemokines act as important mediators of chronic inflammation and the tumour inflammatory response. However, there is limited information on chemokines in hepatocellular carcinoma (HCC), a disease for which almost all cases are derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. The protumor role was confirmed in clinical samples from HCC patients. CXCL1 enhanced tumorigenesis in the hepatic inflammatory microenvironment directly by acting on tumour cells and indirectly through promoting the recruitment of macrophages. The increase in the number of macrophages in the tumour microenvironment (TME) promoted tumour cell epithelial-mesenchymal transition (EMT) and significantly increased CXCL1 levels in the TME partly through NF-κB/IL-1 β activation. To investigate the potential therapeutic value of CXCL1 in HCC with an inflammatory background, an antibody blocking CXCL1 was used alone or combined with the chemotherapy agent doxorubicin (DOX), with the goal of reshaping the TME. It has been shown that blocking CXCL1-CXCR2 inhibits tumour progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to synergistically reduce the number of pro-tumour macrophages in the TME and suppress tumour progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.

目的 探讨深度卷积神经网络在甲状腺结节超声图像的自动检测和良恶性分类中应用价值.方法 回顾性选取1 012 幅甲状腺结节的超声图像并对其进行标记,构建YOLOv5 网络模型,精准定位甲状腺结节所在位置并自动裁减结节所在区域,同时构建GoogLeNet网络模型对裁减后结节的图像进行良恶性分类.结果 在所采集的数据集中,目标检测网络对甲状腺结节位置检测的平均精确度均值为96.2%;分类网络对良恶性结节分类的敏感度为0.885,特异度为0.822,准确度为0.866,AUC值为0.92,显著高于Alex-Net模型(AUC = 0.81)、VGG 模型(AUC = 0.86)和 Mo-bileNet模型(AUC =0.76).结论 深度卷积神经网络模型对超声图像中的甲状腺良恶性结节具有较高的定位和识别能力,有助于提高影像自动诊断的准确性.

Despite the recent progress of medical technology in the diagnosis and treatment of tumors, pancreatic carcinoma remains one of the most malignant tumors, with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation. This paper focuses on the research progress of magnetic resonance imaging, nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma. We also briefly described the achievements of our team in this field, to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

Castleman’s disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. Solid organ involvement is rare, and isolated liver involvement is extremely rare. Here we presented a case of a 59-year-old woman with a hepatic lesion accidentally found by ultrasound. The MRI result indicated primary liver malignancy or liver metastases. 18F-FDG PET/CT could not exclude hepatic malignant tumor due to its high metabolism. Finally, the hepatic CD was confirmed by postoperative pathology.

Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1-Cal has shown remarkable therapeutic effects on ML However, using V1-Cal to improve long-term cardiac function after MI is presently limited by its short half-life. Herein, we co-assembled V1-Cal with a well-known hydrogelator Nap-Phe-Phe-Tyr (NapFFY) to obtain a new supramolecular hydrogel V1-Cal/NapFFY. We found that the hydrogel could significantly enhance the therapeutic effects of V1-Cal on ventricular remodeling reduction and cardiac function improvement in a myocardial infarction rat model. In vitro experiments indicated that co-assembly of V1-Cal with NapFFY significantly increased mechanic strength of the hydrogel, enabling a sustained release of V1-Cal for more than two weeks. In vivo experiments supported that sustained release of V1-Cal from V1-Cal/NapFFY hydrogel could effectively decrease the expression and activation of TRPV1, reduce apoptosis and the release of inflammatory factors in a MI rat model. In particular, V1-Cal/NapFFY hydrogel significantly decreased infarct size and fibrosis, while improved cardiac function 28 days post MI. We anticipate that V1-Cal/NapFFY hydrogel could be used clinically to treat MI in the near future.

目的 探讨肺内单发恶性肿瘤18F-FDG PET/CT显像时最大标准化摄取值(SUVmax)与肿瘤细胞生长指数(Ki-67)的相关性,为患者预后评估提供参考.方法 回顾性分析2016年4月至2018年7月安徽医科大学第二附属医院36例肺内单发恶性肿瘤患者资料,术前均行18 F-FDG PET/CT检查,测量病灶最大层面长径,病灶最大层面长径以3 cm为界,分为≤3 cm肺结节组和>3 cm肺肿块组.测定并计算肿瘤SUVmax早期值、SUVmax延迟期值、ΔSUVmax及滞留指数(RI),并采用Spearman秩相关分析与术后病理类型、Ki-67的相关性;采用非参数检验不同大小病灶的ΔSUVmax值及RI值差异、不同病理类型问ΔSUVmax值及RI值差异.结果 36例肺癌病灶SUVmax早期值为1.21～30.11,中位数为9.350(4.855,14.660).SUVmax延迟期值为1.53～31.71,中位数为10.450(6.938,17.233).原发灶最大层面长径为1.11～8.13 cm,中位数为2.700(2.075,3.668)cm.Ki-67为1％～90％.Spearman秩相关分析结果显示,SUVmax早期值与Ki-67的表达均呈低度相关(r=0.459,P<0.05);SUVmax延迟值、ΔSUVmax与Ki-67的表达均呈显著相关(r=0.584、0.506,P<0.05),RI与Ki-67问呈微弱相关(r=0.183,P=0.286).不同病理类型及不同大小病灶问ΔSUVmax值和RI值比较,差异无统计学意义(P>0.05).结论 肺内单发病灶行18F-FDG PET/CT显像时,不同肿瘤大小、病理类型对ΔSUVmax值和RI值影响不大.SUVmax越高,表明肿瘤增殖活性越大,可预估患者预后.

目的 核素肾动态显像评估12种肾小球滤过率(GFR)计算公式在估算肾脏疾病患者GFR中适用性.方法 选择肾脏疾病患者137例,其中男性84例,女性53例;年龄16～85岁,中位年龄52.5岁;慢性肾脏病(CKD)84例,非CKD53例.行99m锝-二乙三胺五乙酸(99mTc-DTPA)肾动态单光子发射体层摄影术(SPECT)测定GFR.以SPECT所测得的GFR(iGFR)作为参考标准,以临床应用的12种方程(如MDRD公式、CKD-EPI、CG公式、Hojs公式、Filler公式)估算GFR(eGFR)为对照,分析各eGFR与iGFR的相关性、偏差、精确度、准确率、一致性及各公式预测早期CKD[或肾功能下降iGFR＜60mL/(min·1.73 m2)]诊断效能.结果 各eGFR与iGFR均显示相关性(P＜0.05).在数值估算上,CKD组中CKD-EPI糖尿病估算的eGFR与iGFR有较小偏差、较高精确度、较高符合率及一致性,非CKD组一致性超过预定的界限.12种公式预测早期CKD[或肾功能下降iGFR＜60 mL/(min·1.73m2)]诊断效能受试者工作特性(ROC)曲线下面积示CKD-EPI糖尿病测量的eGFR曲线下面积、Youden指数最大,非CKD组Hojs公式、Filler公式测量的eGFR曲线下面积、Youden指数最大.结论 12种公式预测的eGFR均存在不同程度偏差,CKD-EPI糖尿病在CKD、非 CKD两组中预测GFR值最适用;CKD-EPI糖尿病预测CKD组早期CKD发生诊断效能最大,Hojs公式、Filler公式预测非CKD组早期肾功能下降[GFR＜60 mL/(min·1.73 m2)]发生诊断效能最大.

1213 Introduction: To explore the use of 99mTc-RBC SPECT dynamic scan for spleen imaging and analyze the spleen characteristics of time-radioactivity curve(T-A curve). Methods: In the control group, there were 1 healthy volunteer and 8 gastrointestinal bleeding patients. In the experimental group, there were 3 patients with obvious decrease of whole blood cells and splenomegaly. Pyrophosphate was intravenously injected through elbow, and after 20 mins 99mTc other was intravenously injected through the other side, and the dynamic collection of the upper abdomen was started simultaneously. Physicians manually delineated the regions of interest in the liver and spleen of the two groups, and obtained the T-A curve of the liver and spleen. Then the curve was fitted to a straight line after 5 mins, and the α angle (between the fitted straight line and the positive half of the x-axis) was measured to realize semi-quantitative analysis. Results: In control group the shape of T-A curve of healthy volunteers was consistent with that of gastrointestinal bleeding patients, which showed an approximate vertical rise at the beginning, and then an approximate horizontal linear, and their α angles were similar. While the T-A curve in the experimental group was continuously rising. For 2 male patients in the experimental group, they recovered obviously in the blood RT after splenectomy, while the other female patient had no operation and was still anemic during the follow-up. Conclusion:99mTc-labelled RBC SPECT dynamic scan realized spleen imaging and the semi-quantitative could be used for preoperative diagnosis of hypersplenism.

目的 研究microRNA-200a(miR200a)影响肝细胞癌的进展及调控索拉非尼治疗效果.方法 构建人肝癌细胞miR200a稳转细胞株:miR200a过表达、对照组(Control)、miR200a敲低.采用qRT-PCR法检测各转染细胞株miRNA表达量,MTT的方法检测细胞活力,Western blot分析各目标蛋白表达量;Transwell法检测肝癌细胞迁移、侵袭能力.转染细胞株添加索拉非尼,复测MTT及Western blot,验证miR200a调控索拉非尼对细胞的作用和相应蛋白表达量变化,SPF级BALB/c-nu雄鼠18只,随机分为3组,每组6只.每组皮下种植miR200a过表达、Control、miR200a敲低细胞,待成瘤后每组裸鼠每天注射索拉非尼,连续14 d,处死裸鼠,取出瘤体,计算肿瘤体积,免疫组化验证瘤体目标蛋白表达及定位.结果 上调miR200a不仅可以抑制人肝癌细胞的细胞活力及迁移侵袭能力,还可以降低SIRT1的表达.并且上调miR200a明显减小裸鼠的肿瘤体积.结论 上调miR200a可以负性调控人肝癌细胞的增殖和迁移能力,并增加索拉非尼的药物疗效,这种作用可能是通过调控SIRT1表达来完成.

Purpose. To precisely quantify split glomerular filtration rate by Tc-99m-DTPA renal dynamic imaging and plasma clearance in order to increase its consistency among doctors. Methods. Tc-99m-DTPA renal dynamic imaging was performed according to the conventional radionuclide renal dynamic imaging by five double-blinded doctors independently and automatically calculated split GFR, namely, gGFR. Moreover, the conventional radionuclide renal dynamic imaging was assessed to only outline the kidney, blank background, and automatically calculated split GFR, gGFR′. The total GFR value of patients, tGFR, was obtained by the double-plasma method. According to the formula, Precise GFR pGFR=gGFR′/gGFR′+gGFR′×tGFR. The precise GFR value of the divided kidney, pGFR, was calculated. The Kendall’s W test was used to compare the consistency of gGFR and pGFR drawn by five physicians. Results. According to Kendall’s W consistency test, Kendall’s coefficient of concordance was 0.834, p=0.0001 using conventional method. The same five doctors used blank background again and the same standard Gates method to draw the kidneys, which automatically calculated gGFR′. Using input formula, the pGFR was calculated and Kendall’s W consistency test (Kendall’s coefficient of concordance=0.956, p=0.0001). Conclusion. The combination of Tc-99m-DTPA renal dynamic imaging combined with the double-plasma method could achieve accurate split GFR, and because of the omission of influence factors, the consistency of pGFR obtained by different doctors using this method was significantly higher than that of conventional Tc-99m-DTPA renal dynamic imaging.

Recently, immune response modulation at the epigenetic level is illustrated in studies, but the possible function of RNA 5-methylcytosine (m5C) modification in cell infiltration within the tumor microenvironment (TME) is still unclear. Three different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above three identified patterns. A low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. A small amount of effective immune infiltration was seen in the high m5C-score subtype, indicating the dismal patient survival. Our study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out five potential drugs for PTC based on this m5C-score model. m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME.

合成了一种可特异性结合纤维蛋白-纤维连接蛋白的早期血栓显像剂131 I-YSSCREKA肽(酪氨酸-(D)丝氨酸-(D)丝氨酸-半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸),对其标记、SPECT显像及初步生物学性能进行研究.结果表明:YSSCREKA八肽在室温下通过氯胺-T法反应5 min的标记率为(77.2±1.1)％(n=3),放射化学纯度为(90.0±3.1)％(n=3),体外稳定性较好.新西兰家兔SPECT显像显示在131 I-YSSCREKA肽注射后20 h血栓能较清晰地显像,血栓/血放射性比值为1.36.SD大鼠生物分布实验显示:20 h 131 I-YSSCREKA肽在血栓中的摄取率为(0.19±0.06)ID％/g(n=5),血栓/肌肉及血栓/血放射性比值分别为3.80和1.90.131 I-YSSCREKA肽有可能作为早期血栓的显像剂,但其在血栓中的摄取率有待于进一步提高.

目的 探讨CT对胃肠道间质瘤(GIST)危险度分级的临床意义.方法 收集经病理确诊的62例GIST患者的CT资料.根据病理结果将其分为极低危险、低度危险、中度危险、高度危险4个等级,分析不同危险度GIST与CT征象之间的关系.结果 极低危险、低度危险、中度危险及高度危险GIST分别为5例、20例、11例及26例.不同危险度的GIST在肿瘤最大径、有无液化、发病部位、强化方式方面差异均有统计学意义(P<0.05),而在不同危险度中钙化、生长方式、强化程度及各期CT值方面无统计学差异(P>0.05).结论 不同危险度的GIST CT影像学表现存在一定差异,肿瘤最大径、液化和强化方式有助于GIST无创危险度分级,钙化、生长方式及强化程度无明显价值.