[Predicting response to non-small cell lung cancer immunotherapy using pre-treatment contrast-enhanced CT texture-based classification].

Objective: To explore the value of pre-treatment contrast-enhanced computed tomography (CT)-based texture analysis in predicting response to non-small cell lung cancer (NSCLC) immunotherapy. Methods: From January to July 2018, a total of 51 lesions from 42 patients with advanced non-small cell lung cancer receiving immunotherapy at Shanghai Chest Hospital were selected in this retrospective study. Pre-treatment contrast-enhanced CT-based texture features were extracted by MaZda software. Ten optimal texture features were chosen based on three different methods: Fisher coefficient, mutual information measure (MI) and minimization of classification error probability combined average correlation coefficients(POE+ ACC), respectively. According to the efficacy of the first immunotherapy, 51 lesions were divided into non-progressive disease (non-PD, n=26) and progressive disease (PD, n=25). The differences were tested in each texture feature set between the two groups. The immunotherapy effects of target lesions were analyzed by principal component analysis(PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA). The sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) were calculated. The area under the curve (AUC) was used to quantify the predictive accuracy of the three analysis models for each texture feature set and compare them with the actual classification results. Results: In all of three texture feature sets, the texture parameter differences of Perc.50%, Perc.90%, "S(5, 5)SumEntrp" and "S(4, 4)SumEntrp" were higher in PD group than those in non-PD group (all P<0.05). The classification result of texture feature set chosen by POE+ ACC and analyzed by NDA was identified as the best model (AUC=0.802, 95%CI: 0.674-0.930), and its sensitivity, specificity, accuracy, PPV and NPV were 72%, 88.5%, 80.4%, 85.7%, 76.7%, respectively. Conclusion: Pre-treatment contrast-enhanced CT-based texture characteristics of NSCLC may function as non-invasive biomarkers for the evaluation of response to immunotherapy.

[Association between gestational blood pressure and pregnancy induced hypertension or pre-eclampsia].

Objective: To construct the gestational-age-specific blood pressure curve and percentile blood pressure values of pregnant women in Jiangsu Province, and to explore the clinic significance of the blood pressure changes in women whose blood pressure was less than 140/90 mmHg (1 mmHg=0.133 kPa) in each trimester and eventually developed pregnancy induced hypertension (PIH) or pre-eclampsia (PE). Methods: A prospective longitudinal cohort during pregnancy was built. Singleton pregnant women in the first trimester (11-13+6 weeks) were recruited from July 2017 to September 2020 in Nanjing Drum Tower Hospital, and were followed up in the second trimester (19-23+6 weeks), the third trimester (30-33+6 weeks) and approaching the expected date of delivery (35-38+6 weeks). The Viewpoint 6.0 software was used to record pregnancy-related information. The blood pressure was measured by standard methods in our clinic. Least mean square (LMS) function was performed to fit the gestational-age-specific blood pressure curve and percentile blood pressure values were calculated at every follow-up time point. Logistic regression was applied to calculate the OR for the groups with blood pressure ≥95th percentile (P95). Results: There were 3 728 singleton pregnant women invited in this study, including 3 490 normal pregnant women (93.62%, 3 490/3 728), and 238 pregnant women with PIH or PE (6.38%, 238/3 728). Gestational-age-specific blood pressure curve showed that systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) decreased in the second trimester, compared with those in the first and the third trimester, however the fluctuation of blood pressure was low, but regardless of the gestational age, P95 of SBP, DBP and MAP increased by 14, 11 and 11 mmHg respectively, compared with 50th percentile (P50). In the first trimester, the risk of developing PIH or PE finally in pregnant women with blood pressure ≥P95 was 4.36-fold (95%CI: 2.99-6.35) for SBP than women with SBP

Rapid and sensitive LC-MS/MS method for the determination of auraptene in rat plasma and its application in a pharmacokinetic and bioavailability study in rats.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of auraptene, a constituent isolated from Fructus aurantii with potential to combat Alzheimer's disease, in rat plasma. Rat plasma samples were pretreated by protein precipitation with methanol. The analytes were separated by a Waters Sun Fire C18 column (50 mm x 2 mm, 5 µm) and eluted with 1:1000 methanol and formic acid/water (v/v) mobile phase with a flow rate of 0.5 mL/min. Multiple reaction monitoring was used to monitor the transition of the deprotonated auraptene molecule with an m/z of 299.3 [M+H](+), to the product ion with an m/z of 162.9 [M+H](+). Progesterone, with an m/z of 315.2→ 96.9 was used as an internal standard. The limits of detection and of quantification of auraptene in the rat plasma were 1 and 5 ng/mL, respectively. The method was linear in the concentration range of 20- 2000 ng/mL with coefficient correlation of 0.9956. After auraptene (100 mg/kg, p.o.) administration, the maximum plasma concentration and the time taken to reach maximum concentration were 1719.5 ± 384.3 g/mL and 108.0 ± 25.3 min, respectively. The elimination half-life was 108.0 ± 25.3 for auraptene (100 mg/kg, p.o.) and 3.0 ± 0 min for auraptene (2 mg/kg, i.v.). The oral bioavailability was about 8.5%.

Peptidergic innervation of the retinal vasculature and optic nerve head.

Using immunocytochemistry, the authors studied the peptidergic innervation to the vasculature of the optic nerve and retina in the rhesus monkey and rat. In the monkey, beaded nerve fibers immunoreactive to the vasoactive peptides, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal peptide (VIP), are present in the adventitia and perivascular space along the course of the central retinal artery within the optic nerve. The CGRP and SP immunoreactivities fully co-localize. Perivascular peptidergic nerve fibers terminate as the blood vessel enters the globe and do not follow the branches of the central retinal artery inside the eye. Within the substance of the optic nerve behind the lamina cribrosa, small blood vessels occasionally are supplied with CGRP-, SP-, and sometimes NPY- or VIP-immunoreactive nerve fibers. Of special note, fine nerve fibers not clearly related to blood vessels are seen within the lamina cribrosa; their simultaneous immunoreactivity to CGRP and SP suggests a sensory function. In the rat as in the monkey, the retinal arterioles beyond the surface of the optic disc lack evident peptidergic innervation. Perhaps an explanation for the known physiologic reactivity of the retinal circulation to neurohumors in the absence of recognizable peripheral innervation can be based on comparison to the brain where intraparenchymal blood vessels may be regulated by local neurons. Since the inner plexiform layer has abundant amacrine-derived nerve processes containing classical neurotransmitters and/or neuropeptides, a local mechanism coupled to intrinsic retinal activity might contribute to the regulation of the circulation.

Dynamic CT of solitary pulmonary nodules: comparison of contrast medium distribution characteristic of malignant and benign lesions.

BACKGROUND: To prospectively assess the role of the dynamic contrast-enhanced CT enhancement characteristics in distinguishing malignant form of benign solitary pulmonary nodules. METHODS: The study included 87 patients (59 men, 28 women; median age, 59 years) with 87 solitary pulmonary nodules. In all cases, dynamic CT images were obtained before and 20, 30, 45, 60, 75, 90, 120 s, 3, 5, 9, 12, 15 and 20 min after injection of contrast medium. Peak enhancement attenuation value, net enhancement attenuation value, the slope of enhancement, enhancement ratio, outflow of contrast medium (washout), washout ratio and the slope of washout ratio were assessed. Statistical analyses were performed with the Mann-Whitney test, χ(2) test, and receiver-operating characteristic curves. RESULTS: There were 52 malignant and 35 benign nodules. There were no significant differences in net enhancement value, enhancement ratio and the slope of enhancement ratio between malignant and benign nodules (P > 0.05). Malignant nodules showed smaller outflow of contrast medium than did benign nodules. With 12.4HU or lower washout as a cutoff value, the sensitivity and specificity for malignancy were 52.5 and 65.0 %, respectively. With 18.9 % or lower washout ratio as a cutoff value, sensitivity and specificity for malignancy were 60.0 and 75.0 %, respectively. With 0.0180 %/s or lower slope of washout ratio as a cutoff value, sensitivity and specificity for malignancy were 60.0 and 80.0 %, respectively. CONCLUSIONS: Dynamic contrast-enhanced CT is helpful in differentiating malignant from benign solitary pulmonary nodules. Smaller washout of contrast enhancement is a predictor that a lesion is malignant.

Novel functional magnetic resonance imaging biomarkers for assessing response to therapy in hepatocellular carcinoma.

The established and adapted image biomarkers based on size for tumor burden measurement continue to be applied to hepatocellular carcinoma (HCC) as size measurement can easily be used in clinical practice. However, in the setting of novel targeted therapies and liver directed treatments, simple tumor anatomical changes can be less informative and usually appear later than biological changes. Functional magnetic resonance imaging (MRI) has a potential to be a promising technique for assessment of HCC response to therapy. In this review, we discuss various functional MRI biomarkers that play an increasingly important role in evaluation of HCC response after treatment.