Factors associated with overdiagnosis of benign pulmonary nodules as malignancy: a retrospective cohort study.

OBJECTIVE: To establish a preoperative model for the differential diagnosis of benign and malignant pulmonary nodules (PNs), and to evaluate the related factors of overdiagnosis of benign PNs at the time of imaging assessments. MATERIALS AND METHODS: In this retrospective study, 357 patients (median age, 52 years; interquartile range, 46-59 years) with 407 PNs were included, who underwent surgical histopathologic evaluation between January 2020 and December 2020. Patients were divided into a training set (n = 285) and a validation set (n = 122) to develop a preoperative model to identify benign PNs. CT scan features were reviewed by two chest radiologists, and imaging findings were categorized. The overdiagnosis rate of benign PNs was calculated, and bivariate and multivariable logistic regression analyses were used to evaluate factors associated with benign PNs that were over-diagnosed as malignant PNs. RESULTS: The preoperative model identified features such as the absence of part-solid and non-solid nodules, absence of spiculation, absence of vascular convergence, larger lesion size, and CYFRA21-1 positivity as features for identifying benign PNs on imaging, with a high area under the receiver operating characteristic curve of 0.88 in the validation set. The overdiagnosis rate of benign PNs was found to be 50%. Independent risk factors for overdiagnosis included diagnosis as non-solid nodules, pleural retraction, vascular convergence, and larger lesion size at imaging. CONCLUSION: We developed a preoperative model for identifying benign and malignant PNs and evaluating factors that led to the overdiagnosis of benign PNs. This preoperative model and result may help clinicians and imaging physicians reduce unnecessary surgery.

The effect of tumor vascular remodeling and immune microenvironment activation induced by radiotherapy: quantitative evaluation with magnetic resonance/photoacoustic dual-modality imaging.

Background: Tumor radiotherapy combined with immunotherapy for solid tumors has been proposed, but tumor vascular structure abnormalities and immune microenvironment often affect the therapeutic effect of tumor, and multimodal imaging technology can provide more accurate and comprehensive information in tumor research. The purpose of this study was to evaluate the dynamic monitoring of tumor blood vessels and microenvironment induced by radiotherapy by magnetic resonance/photoacoustic (MR/PA) imaging, and to explore its application value in radiotherapy combined with immunotherapy. Methods: The tumor-bearing mice were randomly allocated into six groups, which received different doses of radiation therapy (2 Gy ×14 or 8 Gy ×3) and anti-programmed death ligand-1 (PD-L1) antibody for two consecutive weeks. MR/PA imaging was used to noninvasively evaluate the response of tumor to different doses of radiotherapy, combined with histopathological techniques to observe the tumor vessels and microenvironment. Results: The inhibitory effect of high-dose radiotherapy on tumors was significantly greater than that of low-dose radiotherapy, with the MR images revealing that the signal intensity decreased significantly (P<0.05). Compared with those in the other groups, the tumor vascular density decreased significantly (P<0.01), and the vascular maturity index increased significantly in the low-dose group (P<0.05). The PA images showed that the deoxyhemoglobin and total hemoglobin levels decreased and the SO2 level increased after radiation treatment (P<0.05). In addition, the high-dose group had an increased number of tumor-infiltrating lymphocytes (CD4+ T and CD8+ T cells) (P<0.01, P<0.05) and natural killer cells (P<0.001) and increased PD-L1 expression in the tumors (P<0.05). The combination of radiotherapy and immunotherapy increased the survival rate of the mice (P<0.05), and a regimen of an 8 Gy dose of radiation combined with immunotherapy inhibited tumor growth and increased the survival rate of the mice to a greater degree than the 2 Gy radiation dose with immunotherapy combination (P=0.002). Conclusions: Differential fractionation radiotherapy doses exert biological effects on tumor vascular and the immune microenvironment, and MR/PA can be used to evaluate tumor vascular remodeling after radiotherapy, which has certain value for the clinical applications of radiotherapy combined with immunotherapy.

Diagnostic accuracy of glioma pseudoprogression identification with positron emission tomography imaging: a systematic review and meta-analysis.

Background: Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However, there is some controversy concerning the diagnostic accuracy of PET using different radiotracers to differentiate between glioma pseudoprogression (PsP) and true progression (TPR). The purpose of this meta-analysis was to systematically evaluate the methodological quality and clinical value of original studies for distinguishing PsP from TPR in glioma. Methods: The Medline, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception until September 1, 2022. Retrieved clinical studies only investigated the PsP cases but did not include the cases of radiation necrosis or other treatment-related changes. Eligible studies were screened for data extraction and evaluated by 2 independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A random effects model was used to describe summary receiver operating characteristics. Meta-regression and subgroup analyses were applied to identify any sources of heterogeneity. Results: The meta-analysis included 20 studies, comprising 317 (30.9%) patients with PsP and 708 (69.1%) with TPR. The summary sensitivity and specificity of general PET for identifying PsP were 0.86 [95% confidence interval (CI): 0.77-0.91] and 0.84 (95% CI: 0.79-0.88), respectively. The statistical heterogeneity was explained by sample size, study design, World Health Organization (WHO) grade, gold standard, and radiotracer type. The summary sensitivity and specificity of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET PET) were 0.80 (95% CI: 0.68-0.88) and 0.81 (95% CI: 0.75-0.85), respectively. The maximum tumor-to-brain ratio (TBRmax) and the mean tumor-to-brain ratio (TBRmean) both showed excellent diagnostic performance in 18F-FET studies, the summary sensitivity was 0.83 (95% CI: 0.72-0.91) and 0.79 (95% CI: 0.65-0.98), respectively, and the specificity was 0.76 (95% CI: 0.68-0.84) and 0.78 (95% CI: 0.64-0.88), respectively. Conclusions: PET imaging is generally accurate in identifying glioma PsP. Considering the credibility of meta-evidence and the practicability of using radiotracer, 18F-FET PET holds the highest clinical value, while TBRmax and TBRmean should be regarded as reliable parameters. PET used with the radiotracers and multiple-parameter combinations of PET with magnetic resonance imaging (MRI) and radiomics analysis have broad research and application prospects, whose diagnostic values for identifying glioma PsP warrant further investigation.

Prediction of brain age using quantitative parameters of synthetic magnetic resonance imaging.

Objective: Brain tissue changes dynamically during aging. The purpose of this study was to use synthetic magnetic resonance imaging (syMRI) to evaluate the changes in relaxation values in different brain regions during brain aging and to construct a brain age prediction model. Materials and methods: Quantitative MRI was performed on 1,000 healthy people (≥ 18 years old) from September 2020 to October 2021. T1, T2 and proton density (PD) values were simultaneously measured in 17 regions of interest (the cerebellar hemispheric cortex, pons, amygdala, hippocampal head, hippocampal tail, temporal lobe, occipital lobe, frontal lobe, caudate nucleus, lentiform nucleus, dorsal thalamus, centrum semiovale, parietal lobe, precentral gyrus, postcentral gyrus, substantia nigra, and red nucleus). The relationship between the relaxation values and age was investigated. In addition, we analyzed the relationship between brain tissue values and sex. Finally, the participants were divided into two age groups: < 60 years old and ≥ 60 years old. Logistic regression analysis was carried out on the two groups of data. According to the weight of related factors, a brain age prediction model was established and verified. Results: We obtained the specific reference value range of different brain regions of individuals in different age groups and found that there were differences in relaxation values in brain tissue between different sexes in the same age group. Moreover, the relaxation values of most brain regions in males were slightly higher than those in females. In the study of age and brain relaxation, it was found that brain relaxation values were correlated with age. The T1 values of the centrum semiovale increased with age, the PD values of the centrum semiovale increased with age, while the T2 values of the caudate nucleus and lentiform nucleus decreased with age. Seven brain age prediction models were constructed with high sensitivity and specificity, among which the combined T1, T2 and PD values showed the best prediction efficiency. In the training set, the area under the curve (AUC), specificity and sensitivity were 0.959 [95% confidence interval (CI): 0.945-0.974], 91.51% and 89.36%, respectively. In the test cohort, the above indicators were 0.916 (95% CI: 0.882-0.951), 89.24% and 80.33%, respectively. Conclusion: Our study provides specific reference ranges of T1, T2, and PD values in different brain regions from healthy adults of different ages. In addition, there are differences in brain relaxation values in some brain regions between different sexes, which help to provide new ideas for brain diseases that differ according to sex. The brain age model based on synthetic MRI is helpful to determine brain age.

Heroin Addiction Induces Axonal Transport Dysfunction in the Brain Detected by In Vivo MRI.

Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport at different stages of heroin addiction. Rat models of heroin addiction (HA) and prolonged heroin addiction (PHA) were established by injecting rats with heroin at different stages. Heroin-induced learning and memory deficits were evaluated in the Morris water maze (MWM), and MEMRI was used to dynamically evaluate axonal transport in the olfactory pathway. The expression of proteins related to axonal structure and function was also assessed by Western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes, and protein levels of neurofilament heavy chain (NF-H) were analyzed by immunofluorescence staining. HA rats, especially PHA rats, exhibited worse spatial learning and memory than control rats. Compared with HA rats and control rats, PHA rats exhibited significantly longer escape latencies, significantly fewer platform-location crossings, and significantly more time in the target quadrant during the MWM test. Mn2+ transport was accelerated in HA rats. PHA rats exhibited severely reduced Mn2+ transport, and the axonal transport rate (ATR) was significantly lower in these rats than in control rats (P < 0.001). The levels of cytoplasmic dynein and kinesin-1 were significantly decreased in the PHA group than in the control group (P < 0.001); additionally, the levels of energy-related proteins, including cytochrome c oxidase (COX) IV and ATP synthase subunit beta (ATPB), were lower in the PHA group (P < 0.001). The brains of heroin-exposed rats displayed an abnormal ultrastructure, with neuronal apoptosis and mitochondrial dysfunction. Heroin exposure decreased the expression of NF-H, as indicated by significantly reduced staining intensities in tissues from HA and PHA rats (P < 0.05). MEMRI detected axonal transport dysfunction caused by long-term repeated exposure to heroin. The main causes of axonal transport impairment may be decreases in the levels of motor proteins and mitochondrial dysfunction. This study shows that MEMRI is a potential tool for visualizing axonal transport in individuals with drug addictions, providing a new way to evaluate addictive encephalopathy.

Purification and partial characterisation of a cathepsin L-like proteinase from sea cucumber (Stichopus japonicus) and its tissue distribution in body wall.

A cathepsin L-like proteinase (CLP) with molecular weight of 30.9 kDa from the gut of sea cucumber (Stichopus japonicas, S. japonicus) was isolated and purified to homogeneity by several chromatographic procedures. The enzyme exhibited optimum activity at pH 5.0-5.5 and 50 °C, and showed thermostability up to 40 °C. The enzyme activity was completely inhibited by Zn(2+), strongly inhibited by Fe(2+) and Cu(2+), drastically reduced by cysteine proteinase inhibitors, but slightly enhanced by thiol-activating agents. The enzyme efficiently hydrolysed the specific substrate of cathepsin L, but hardly hydrolysed the specific substrates for cathepsin B, cathepsin H and cathepsin K. Immunohistochemical studies indicated that the CLP was more abundant in the epidermis rather than in the dermis of S. japonicus body wall. The distribution of CLP showed positive correlation with autolysis rate. Therefore, the relationship between CLP and autolysis deserved further study.