Synthesis and preclinical evaluation of a novel molecular probe [18F]AlF-NOTA-PEG2-Asp2-PDL1P for PET imaging of PD-L1 positive tumor.

Immunotherapy has brought great benefits to cancer patients, but only some patients benefit from it. Noninvasive, real-time and dynamic monitoring of the effectiveness of immunotherapy through PET imaging may provide assistance for the treatment plan of immunotherapy. In this study, we designed and synthesized a new targeted PD-L1 peptide NOTA-PEG2-Asp2-PDL1P, which was labeled with nuclide 18F to obtain a new imaging agent [18F]AlF-NOTA-PEG2-Asp2-PDL1P. The total radiochemical yield of [18F]AlF-NOTA-PEG2-Asp2-PDL1P was 13.7 % (Uncorrected radiochemical yield, n > 5). [18F]AlF-NOTA-PEG2-Asp2-PDL1P achieved high radiochemical purity (>95 %) with a molar activity more than 51.2 GBq/µmol. [18F]AlF-NOTA-PEG2-Asp2-PDL1P exhibited good hydrophilicity and had good stability both in vivo and in vitro, it can specifically targets B16F10 tumor with PD-L1 expression, and had a relatively high retention in tumor, a relatively fast clearance in vivo and a higher tumor-to-non-target ratio, all of which could make [18F]AlF-NOTA-PEG2-Asp2-PDL1P a potential tracer for PD-L1 prediction before clinical immunotherapy.

Ultrasonographic scoring system for the diagnosis of adnexal torsion.

PURPOSE: To establish the utility of an ultrasonographic scoring system for the diagnosis of adnexal torsion. METHODS: We retrospectively analyzing 358 adnexal torsion cases. Using Pearson's χ2 test we determined whether ultrasonographic signs were significantly associated with adnexal torsion. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of the system. Ultimately by using binary logistic regression we established a precise and convenient scoring system. RESULTS: The torsion score was based on five criteria that were identified to be independently associated with adnexal torsion: (1) abnormal position of the index adnexa (odds ratio [OR], 2.311); (2) presence of a mass or cyst (OR, 3.495); (3) unilateral ovarian enlargement (OR, 3.051); (4) vascular pedicle twisting (OR, 2.105); and (5) peripheral hypervascularity of the corpus luteum with ovarian edema(encapsulating cyst sign) (OR, 4.164).patients with torsion who scored 0, have a predicted diagnosis rate of 20.9%; patients whose scores were 1,2 have a predicted probability of 41.8% and 66.15%, respectively. For patients with torsion scores of 3, 4, and 5, predicted diagnosis rates were 84.16%, 93.52%, and 98.27%, respectively. CONCLUSION: The ultrasonographic scoring system is feasible and precisely diagnoses adnexal torsion using ultrasound.

GLP-1 improves the neuronal supportive ability of astrocytes in Alzheimer's disease by regulating mitochondrial dysfunction via the cAMP/PKA pathway.

The glucagon-like peptide-1 (GLP-1) was shown to have neuroprotective effects in Alzheimer's disease (AD). However, the underlying mechanism remains elusive. Astrocytic mitochondrial abnormalities have been revealed to constitute important pathologies. In the present study, we investigated the role of astrocytic mitochondria in the neuroprotective effect of GLP-1 in AD. To this end, 6-month-old 5 × FAD mice were subcutaneously treated with liraglutide, a GLP-1 analogue (25 nmol/kg/qd) for 8 weeks. Liraglutide ameliorated mitochondrial dysfunction and prevented neuronal loss with activation of the cyclic adenosine 3',5'-monophosphate (cAMP)/phosphorylate protein kinase A (PKA) pathway in the brain of 5 × FAD mice. Next, we exposed astrocytes to ß-amyloid (Aß) in vitro and treated them with GLP-1. By activating the cAMP/PKA pathway, GLP-1 increased the phosphorylation of DRP-1 at the s637 site and mitigated mitochondrial fragmentation in Aß-treated astrocytes. GLP-1 further improved the Aß-induced energy failure, mitochondrial reactive oxygen species (ROS) overproduction, mitochondrial membrane potential (MMP) collapse, and cell toxicity in astrocytes. Moreover, GLP-1 also promoted the neuronal supportive ability of Aß-treated astrocytes via the cAMP/PKA pathway. This study revealed a new mechanism behind the neuroprotective effect of GLP-1 in AD.

Metabolomics as a potential method for predicting thyroid malignancy in children and adolescents.

PURPOSE: To identify potential metabolic biomarkers for distinguishing malignant and benign thyroid nodules in children and adolescents using a metabolomics approach. METHODS: A total of 96 consecutive patients (median age 14.29 ± 2.31 years, range 9-18 years) who underwent thyroidectomy and 40 healthy controls were enrolled. Patients were assigned to the papillary thyroid carcinoma and benign thyroid adenoma groups according to postoperative pathologic biopsy. Plasma samples were preoperatively collected, and multivariate analysis was performed to identify differential metabolites. RESULTS: Papillary thyroid carcinoma could be distinguished not only from healthy serum but also from benign thyroid adenoma according to the metabolic profiles. A total of 17 metabolites were identified. Compared with those from benign thyroid adenoma patients and healthy controls, the metabolites from papillary thyroid carcinoma patients, including leucine, lactate, alanine, glycine, acetate, lysine and choline, were increased, while glucose was decreased. CONCLUSION: The metabolomics method based on proton nuclear magnetic resonance has great potential for identifying papillary thyroid carcinoma in children and adolescents. Lactate and glycine may be used as potential serum markers for the diagnosis of papillary thyroid carcinoma.

The antibiotic clofoctol suppresses glioma stem cell proliferation by activating KLF13.

Gliomas account for approximately 80% of primary malignant tumors in the central nervous system. Despite aggressive therapy, the prognosis of patients remains extremely poor. Glioma stem cells (GSCs) which considered as the potential target of therapy for their crucial role in therapeutic resistance and tumor recurrence, are believed to be key factors for the disappointing outcome. Here, we took advantage of GSCs as the cell model to perform high-throughput drug screening and the old antibiotic, clofoctol, was identified as the most effective compound, showing reduction of colony-formation and induction of apoptosis of GSCs. Moreover, growth of tumors was inhibited obviously in vivo after clofoctol treatment especially in primary patient-derived xenografts (PDXs) and transgenic xenografts. The anticancer mechanisms demonstrated by analyzing related downstream genes and discovering the targeted binding protein revealed that clofoctol exhibited the inhibition of GSCs by upregulation of Kruppel-like factor 13 (KLF13), a tumor suppressor gene, through clofoctol's targeted binding protein, Upstream of N-ras (UNR). Collectively, these data demonstrated that induction of KLF13 expression suppressed growth of gliomas and provided a potential therapy for gliomas targeting GSCs. Importantly, our results also identified the RNA-binding protein UNR as a drug target.

Human papillomavirus infections among women with cervical lesions and cervical cancer in Eastern China: genotype-specific prevalence and attribution.

BACKGROUND: Cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent high-risk human papillomavirus (HPV) infection. HPV genotype prevalence varies with severity of cervical lesions, patient age and geographical location. The aim of this study was to investigate HPV genotypes prevalence and attribution according to the severity of cervical lesions among Chinese women. METHOD: A 4-year surveillance study was performed. A total of 1664 female patients were included and their cervical histological diagnosis consisted of cervical intraepithelial neoplasia grade 1 (CIN1, 376 cases), grade 2 (CIN2, 408 cases), grade 3 (CIN3, 336 cases) and invasive cervical cancers (ICC, 544 cases). HPV genotypes prevalence and attribution to cervical lesions were calculated and analyzed. The 95% confidence interval (CI) for proportion was also calculated. RESULTS: HPV positivity rates increased directly with cervical lesions severity (72.4% for CIN1, 81.4% for CIN2, 88.1% for CIN3 and 90.4% for ICC). Infections with multiple HPV types were inversely related to cervical lesions severity. HPV16, 52, 31, 33 and 58 were the most prevalent genotypes in ICC. 49.1% of squamous cell carcinoma, 65.1% of adenocarcinoma and 12.0-43.3% of cervical intraepithelial neoplasia could be attributed to vaccine-covered high-risk genotypes (HPV16/18). Inclusion of HPV52 and HPV31 in future vaccines would provide the highest marginal benefit in protection for individuals residing in this region. CONCLUSIONS: These findings provide information about HPV genotypes in this region which may be important to target with future vaccination and screening programs.

Human papillomavirus prevalence and genotypes distribution among female outpatients in Qingdao, East China.

Persistent infection with human papillomavirus, especially high risk ones, is a necessary cause of cervical cancer. This study aimed to investigate the distribution of HPV genotypes in female outpatients from Qingdao, East China. A total of 4,534 cervical swabs from women visiting this medical institution for gynecologic care were included. HPV genotypes were examined by a PCR-based hybridization gene chip assay and liquid-based cytology analysis was used to evaluate cervical cytology. The overall HPV prevalence in this study was 32.2% (1,459/4,534). A total of 23 HPV genotypes were identified and the five most prevalent ones were HPV16 (16.1%), HPV52 (8.9%), HPV58 (7.9%), HPV6 (7.0%), and HPV53 (6.5%). Age-specific prevalence of HPV exhibited one peak at the youngest age group and the HPV positive rate decreased gradually with age growth. But high risk HPV infections were more prevalent among aged women. Besides, association between cervical cytology and HPV infection was also determined, 27.2% (1124/4,126) of women with normal cytology were HPV positive while 82.1% (335/408) of women with abnormal cytology were HPV positive. These findings give new epidemiological data and may provide guidance for the vaccination program in this area.