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 immunohisto-chemistry 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 the effects of spinal cord injury(SCI)on neuropathic pain(NP)and cognitive dysfunction in mice,as well as the activation of neurons in the anterior cingulate cortex(ACC),in order to provide experimental evidence for the connection between NP and cognitive dysfunction following SCI.Methods:Ten 8-week-old male C57BL/6J mice were used to prepare a model of spinal cord hemisection(SCI).Pain behavior and cognitive function of mice after SCI were assessed using von Frey,thermal stimulation,and Morris water maze behavioral experi-ments.Immunofluorescence staining were used to analyze the expression of c-Fos and GAD67/VGLUT2 positive cells in the anterior cingulate cortex(ACC)of the SCI model mice.Results:Compared with the Sham group,the SCI group of mice showed a significant decrease in mechanical threshold and thermal pain threshold(P＜0.05).The Morris water maze results indicated a significantly prolonged escape latency(P＜0.05)and a significant reduction in the use of search strategies for locating the hidden platform.Immunofluorescence results showed a significant increase in the num-ber of c-Fos positive cells in the ACC(P＜0.05),which were mainly co-labeled with excitatory neuron marker VGLUT2 positive cells.Conclusion:SCI leads to abnormal pain behavior and cognitive dysfunction in mice,and it induces the activation of neurons in the ACC,with a predominant activation of excitatory neurons.This study provides morphological evidence for the involvement of excitatory neurons in the ACC in the comorbidity of NP and cognitive impairment following SCI.

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 the effects of spinal cord injury(SCI)on neuropathic pain(NP)and cognitive dysfunction in mice,as well as the activation of neurons in the anterior cingulate cortex(ACC),in order to provide experimental evidence for the connection between NP and cognitive dysfunction following SCI.Methods:Ten 8-week-old male C57BL/6J mice were used to prepare a model of spinal cord hemisection(SCI).Pain behavior and cognitive function of mice after SCI were assessed using von Frey,thermal stimulation,and Morris water maze behavioral experi-ments.Immunofluorescence staining were used to analyze the expression of c-Fos and GAD67/VGLUT2 positive cells in the anterior cingulate cortex(ACC)of the SCI model mice.Results:Compared with the Sham group,the SCI group of mice showed a significant decrease in mechanical threshold and thermal pain threshold(P＜0.05).The Morris water maze results indicated a significantly prolonged escape latency(P＜0.05)and a significant reduction in the use of search strategies for locating the hidden platform.Immunofluorescence results showed a significant increase in the num-ber of c-Fos positive cells in the ACC(P＜0.05),which were mainly co-labeled with excitatory neuron marker VGLUT2 positive cells.Conclusion:SCI leads to abnormal pain behavior and cognitive dysfunction in mice,and it induces the activation of neurons in the ACC,with a predominant activation of excitatory neurons.This study provides morphological evidence for the involvement of excitatory neurons in the ACC in the comorbidity of NP and cognitive impairment following SCI.

Objective:To investigate the expressions of lysine specific demethylase 1 (LSD1) and podoplanin (PDPN) in tongue squamous cell carcinoma and the correlation between LSD1 or PDPN and clinicopathological characteristics or prognosis.Methods:A total of 67 cases of tongue squamous cell carcinoma and corresponding paracancerous normal tissues in the First Affiliated Hospital of Xinjiang Medical University from January 2011 to January 2016 were selected. The expressions of LSD1 and PDPN in cancer and paracancerous tissues were detected by immunohistochemical method, and the patients were followed up for a long time to analyze the correlation between the expression of LSD1 or PDPN and clinicopathological characteristics or prognosis.Results:The expressions of LSD1 and PDPN in tongue squamous cell carcinoma tissues were higher than those in paracancerous tissues, and the differences were statistically significant ( Z=6.089, P<0.001; Z=5.781, P<0.001). The expression intensities of LSD1 and PDPN were significantly different in patients with different clinical stage ( χ2=11.487, P=0.001; χ2=8.111, P=0.004), lymph node metastasis ( χ2=4.772, P=0.029; χ2=6.206, P=0.013) and tumor size ( χ2=5.985, P=0.014; χ2=4.247, P=0.039). The expression intensity of LSD1 was also significantly different in patients with different degrees of differentiation ( χ2=6.660, P=0.010). In univariate analysis, LSD1 expression intensity was negatively correlated with progression-free survival (PFS) and overall survival (OS) ( χ2=18.930, P<0.001; χ2=16.257, P<0.001), PDPN expression intensity was negatively correlated with PFS and OS ( χ2=31.720, P<0.001; χ2=18.390, P<0.001), and tumor size was negatively correlated with PFS and OS ( χ2=5.326, P=0.021; χ2=8.843, P=0.003). Postoperative radiotherapy and clinical stage were positively and negatively correlated with OS respectively ( χ2=4.197, P=0.040; χ2=6.355, P=0.012). In multivariate analysis, LSD1 was an independent risk factor for PFS and OS ( HR=5.743, 95% CI: 1.012-32.579, P=0.048; HR=17.759, 95% CI: 2.303-136.916, P=0.006), PDPN was an independent risk factor for PFS ( HR=4.380, 95% CI: 1.258-15.254, P=0.020), postoperative radiotherapy was a protective factor for PFS and OS ( HR=0.374, 95% CI: 0.157-0.895, P=0.027; HR=0.218, 95% CI: 0.091-0.521, P=0.001), and clinical stage was an independent risk factor for OS ( HR=2.637, 95% CI: 1.107-6.280, P=0.029). In tongue squamous cell carcinoma tissues, the expression of LSD1 was positively correlated with that of PDPN ( rs=0.655, P<0.001). Conclusion:The expressions of LSD1 and PDPN in tongue squamous cell carcinoma are higher than those in adjacent tissues. LSD1 is an independent risk factor for PFS and OS, PDPN is an independent risk factor for PFS, clinical stage is an independent risk factor for OS, and postoperative radiotherapy is a protective factor for PFS and OS. There is a positive correlation between the expressions of LSD1 and PDPN in tongue squamous cell carcinoma, and they can both be used as independent predictors of prognosis in patients with tongue squamous cell carcinoma.

OBJECTIVETo study anti-HIV activity and mechanism of Cynanchum otophyllum glucan sulfate in vitro.

METHODAnti-HIV-1 activity was detected with syncytial formation assay and quantitative P24 enzyme-linked immunosorbent assay (ELISA); cytotoxicity was tested with MTT colorimetric assay. Antiviral mechanism was investigated by fusion inhibition, time of addition and pre-treatment experiments.

RESULTThe 50% inhibition concentrations (IC50) of PS20 for HIV-1(IIIB), HIV-1(Ada-M), and HIV-1(Bal), were 0.26, 0.46, 0.90 micromol x L(-1), respectively. Studies on antiviral mechanism of PS20 showed that target molecule may be viral envelope protein.

CONCLUSIONThe results suggested that PS20 had high anti-HIV activity and was worth to be studied further.

Anti-HIV Agents ; pharmacology ; Cell Fusion ; Cell Line ; Cell Proliferation ; drug effects ; Cynanchum ; chemistry ; Glucans ; isolation & purification ; pharmacology ; HIV-1 ; drug effects ; Humans ; Inhibitory Concentration 50 ; Plant Extracts ; pharmacology ; Plant Roots ; chemistry ; metabolism ; Viral Envelope Proteins ; drug effects