Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [¹⁸F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [¹⁸F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 in vitro and in vivo, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [¹⁸F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [¹⁸F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [¹⁸F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.

Objective To investigate whether recombinant Newcastle disease virus(rL-RVG)induces iron death in gastric cancer cells through Nrf2-GCLC-GPX4 pathway.Methods After human gastric cancer HGC-27 cells were treated with rL-RVG,Newcastle disease virus(NDV)and PBS solution(control group),respectively,cell proliferation,invasion and migration were detected by CCK-8 assay and Transwell invasion assay and cell scratch test.Ferroptosis accelerator(erastin),and nuclear factor E2 related factor 2(Nrf2)accelerator(TBHQ)and inhibitor(ML385)were added respectively as controls.The content of malondialdehyde(MDA)in each treatment group was detected by lipid oxidation kit.The content of reactive oxygen species(ROS)was detected by DCFH-DA fluorescent probe and flow cytometry.Western blotting and immunofluorescence assay were employed to measure the expression levels of Nrf2-GCLC-GPX4 pathway related proteins.Results Compared with the control group,the survival rate of HGC-27 cells were significantly decreased after rL-RVG and NDV treatment in a dose-and time-dependent manner,and the effect was more significant in the rL-RVG treatment group(P＜0.05).The migration and invasion abilities of HGC-27 cells were obviously inhibited in the NDV and rL-RVG treatment groups,and the latter had more notable inhibition than the former.The protein levels of Nrf2,GCLC,SLC7A11 and GPX4 were statistically decreased(P＜0.05),and the contents of MDA and ROS were increased(P＜0.05)in the virus treatment groups than the control group,with the increasing or decreasing trend more significant in the rL-RVG group than the NDV group.What's more,the protein levels of SLC7A11 and GPX4 were decreased in the erastin group(P＜0.05).Compared with the control group,those of Nrf2,GCLC,SLC7A11 and GPX4 were increased in the TBHQ group and decreased in the ML385 group(P＜0.05),while the contents of MDA and ROS were decreased and increased respectively in the above 2 groups(P＜0.05).Compared with the rL-RVG group,the rL-RVG+TBHQ group and rL-RVG+ML385 group had enhanced and reduced protein expressio of Nrf2,GCLC,SLC7A11 and GPX4,respectively(P＜0.05),while the contents of MDA and ROS were in opposite trends(P＜0.05).Conclusion rL-RVG can induce ferroptosis of gastric cancer cells through Nrf2-GCLC-GPX4 pathway,and then inhibit the growth of tumor cells.

Objective To investigate the role of sodium-hyaluronate-modified calcium peroxide nanoparticles(SH-CaO2 NPs)in inducing pyroptosis in human gastric cancer cells and its possible mechanisms.Methods Transmission electron microscopy(TEM),X-ray diffraction(XRD),infrared spectroscopy,and zeta potential test were used to confirm the synthesis of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay were employed to observe the impacts of SH-CaO2 NPs on the migration and proliferation of human gastric cancer cell line HGC-27.The generation of reactive oxygen species(ROS)was observed with confocal laser scanning microscopy(CLSM)and quantified with flow cytometry in the cells after SH-CaO2 NPs treatment or with pretreatment with ROS inhibitor NAC.Furthermore,the effects of pretreatment of NLRP3 inhibitor(MCC950)and Caspase-1 inhibitor(VX765)on the proliferative activity and on expression of their own and their downstream GSDMD in HGC-27 cells were also investigated with CCK-8 assay,immunofluorescence assay and Western blotting.Results TEM images,XRD,infrared spectroscopy,and zeta potential test confirmed the successful preparation of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay showed that application of SH-CaO2 NPs for 24 h significantly inhibited the proliferation of HGC-27 cells(P＜0.001),while,CLSM and flow cytometry indicated the treatment also promoted the production of ROS(P＜0.001).Pretreatment of ROS inhibitor NAC resulted in up-regulation of NLRP3,and increased expression levels of cleaved Caspase-1 and N-terminal fragment of GSDMD(P＜0.001),while pretreatment of both NLRP3 inhibitor and Caspase-1 inhibitor could reverse the process.Conclusion SH-CaO2 NPs inhibit cell viability of human gastric cancer,which may mediate the inflammatory response and pyroptosis by activating the ROS/NLRP3/Caspase-1/GSDMD signaling pathway.

Objective: To compare the clinicopathological characteristics of second primary lung cancer following breast cancer and lung metastases from breast cancer, and then to analyze the risk factors in breast cancer patients with second primary lung tumor. Methods: Clinical data of 55 breast cancer patients with second primary lung tumor and 205 breast cancer patients with solitary pulmonary metastasis in Shandong Cancer Hospital from January 2006 to January 2017 were retrospectively analyzed. The risk factors of primary lung cancer following breast cancer were analyzed using logistic regression model. Results: Second primary lung cancer in patients with first breast cancer accounted for approximately 21.2%(55/260) of pulmonary malignant solitary nodules, and 0.84%(55/6 580) of all breast cancer patients. The median intervals between the diagnosis of second primary lung cancer or lung metastasis and first breast cancer were 52 months and 42 months, respectively. These two groups showed significant difference between age, time interval between diagnoses, breast tumor size, axillary lymph node metastasis, estrogen receptor, molecular subtype (luminal B and triple-negative) and history of radiotherapy (P<0.05 for all). A multivariate logistic regression model confirmed that age (OR=1.088, P<0.001), breast tumor size(OR=0.480, P<0.001), and radiotherapy history (OR=3.460, P=0.004) were all independent factors for second primary lung cancer. Conclusions For isolated pulmonary nodules in patients with breast cancer, especially for those with elder age, larger tumor size and radiotherapy history, we should distinguish the second primary lung cancer from pulmonary metastasis. The treatment regimen for lung metastasis and primary lung cancer in patients with breast cancer are entirely distinct. The timely histopathology examinations for pulmonary nodes in patients with breast cancer are recommended.

Objective To investigate the effect of combined administration of autophagy inhibitor 3?methyladenine/bafilomycin A1 and EGFR inhibitor gefitinib on triple?negative breast cancer MDA?MB?468, MDA?MB?231 cells and estrogen receptor?positive MCF?7 cells. Methods All the cells were treated with 3?methyladenine/bafilomycin A1 and/or gefitinib. The effect of autophagy inhibitor and gefitinib on the cell growth was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to determine the alteration of autophagy?related protein ( such as LC3) and apoptosis?related proteins ( such as caspase?3 and caspase?9) . Results MTT assay showed that the IC50 in the GE+3?MA and GE+BAF groups were (4.1±0.2) μmol/L and (3.8±0.3) μmol/L, significantly lower than that of the gefitinib alone group [(7.0±0.2) μmol/L] in MDA?MB?468 cells (P<0.05). Similarly, the IC50 in the GE+3?MA and GE+BAF groups were (9.7±0.1) μmol/L and (7.7±0.2) μmol/L, significantly lower than that of the gefitinib alone group [(14.7±0.1) μmol/L]in MDA?MB231 cells (P<0.05). The flow cytometry assay revealed that the apoptosis rates of MDA?MB?468 cells in GE, GE+3?MA and GE+BAF groups were (12.43± 3.18)%, (23.37±2.71)% and (18.71±2.81)%, respectively. The apoptosis rates of MDA?MB?231 cells of the GE, GE+3?MA and GE+BAF groups were (12.15±1.82)%, (16.94±2.19)% and (33.83±5.92) %, significantly higher than that of the gefitinib alone group (All P<0.05). The apoptosis rates of the MCF?7 cells were not changed significantly among the three groups (P>0.05). Western blot data showed that the expression levels of LC3 and p?Akt were decreased in the combined groups than that of the gefitinib alone group, while the p?PTEN, caspase?3 and caspase?9 were increased. Conclusions Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA?MB?468 and MDA?MB?231 cells by activation of the PTEN/P13K/Akt pathway. Apoptosis in MDA?MB?468 and MDA?MB?231 cells might be enhanced by the combination treatment through caspase cascade.

Objective To investigate the effect of combined administration of autophagy inhibitor 3?methyladenine/bafilomycin A1 and EGFR inhibitor gefitinib on triple?negative breast cancer MDA?MB?468, MDA?MB?231 cells and estrogen receptor?positive MCF?7 cells. Methods All the cells were treated with 3?methyladenine/bafilomycin A1 and/or gefitinib. The effect of autophagy inhibitor and gefitinib on the cell growth was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to determine the alteration of autophagy?related protein ( such as LC3) and apoptosis?related proteins ( such as caspase?3 and caspase?9) . Results MTT assay showed that the IC50 in the GE+3?MA and GE+BAF groups were (4.1±0.2) μmol/L and (3.8±0.3) μmol/L, significantly lower than that of the gefitinib alone group [(7.0±0.2) μmol/L] in MDA?MB?468 cells (P<0.05). Similarly, the IC50 in the GE+3?MA and GE+BAF groups were (9.7±0.1) μmol/L and (7.7±0.2) μmol/L, significantly lower than that of the gefitinib alone group [(14.7±0.1) μmol/L]in MDA?MB231 cells (P<0.05). The flow cytometry assay revealed that the apoptosis rates of MDA?MB?468 cells in GE, GE+3?MA and GE+BAF groups were (12.43± 3.18)%, (23.37±2.71)% and (18.71±2.81)%, respectively. The apoptosis rates of MDA?MB?231 cells of the GE, GE+3?MA and GE+BAF groups were (12.15±1.82)%, (16.94±2.19)% and (33.83±5.92) %, significantly higher than that of the gefitinib alone group (All P<0.05). The apoptosis rates of the MCF?7 cells were not changed significantly among the three groups (P>0.05). Western blot data showed that the expression levels of LC3 and p?Akt were decreased in the combined groups than that of the gefitinib alone group, while the p?PTEN, caspase?3 and caspase?9 were increased. Conclusions Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA?MB?468 and MDA?MB?231 cells by activation of the PTEN/P13K/Akt pathway. Apoptosis in MDA?MB?468 and MDA?MB?231 cells might be enhanced by the combination treatment through caspase cascade.

Objective To discuss the clinical features and treatment of ureteral obstruction resulted from vena genitalis compression.Methods 2 cases of hydronephrosis resulted from vena genitalis compression were discussed retrospectively,and relevant literatures were reviewed.Both of the 2 patients presenting with mild loin pain,and imaging studies showed hydronephrosis.One patients presenting with left hydronephrosis,and the other showed bilateral hydronephrosis.Imaging study showed ureter obstruction at L3-L4 level.Laparoscopic surgery found vena genitalis crossing and compressing the upper part of the ureter,resulted the upper ureter and pelvis dilation.Laparoscopic excision of vena genitalis were performed on these two cases.Results These patients'symptoms were relieved and hydronephrosis alleviated evidently 3 month after surgery in follow-up.Conclusions Hydronephrosis resulted from vena genitalis compression is a rare clinical manifestation.Classical imaging presents with ureter obstruction at L3-L5 level,at which the vena genitalis crossing the musculi psoas major.Ureter migrates outwards and the upper ureter and pelvis dilate.Pre-operative diagnosis is difficulty,but laparoscopic resection of the vena genitalis to relieve the obstruction of the ureter is recommended.

Objective To assess the value of ultrasonography in distinguishing pharyngoesophageal diverticulum from thyroid nodule.Methods High-frequency sonography was used to detect the size,shape, echo and blood flow of cervix masses in 1219 patients in a lateral decubitus position after drinking water. Results On enhanced power,the image changing rates of pharyngcesophageal diverticulum and thyroid nodule were 71.43% and 14.19% respectively,and their difference was statistically significant(P<0.05). On drinking water,the image change rates of pharyngoesophageal diverticulum and thymid nodule were 100.00% and 1.98% respectively,and their difference was statisfically significant(P<0.05).The detection rates for pharyngoesophageal diverticulum and thyroid nodule were 0.098% and 17.042% respectively. Conclusions Ultrasound examination is of value in distinguishing pharyngoesophageal diverticulum from thyroid nodule in general health check up and regular health examination.