The value of CT-based radiomics in early assessment of chemotherapeutic effect in patients with advanced lung adenocarcinoma: a preliminary study.

BACKGROUND: Computed tomography (CT) is the preferred method for evaluating the therapeutic effect of lung cancer. Radiomics parameters can provide a lot of supplementary information for clinical diagnosis and treatment. PURPOSE: To investigate the value of radiomics features of CT imaging to predict and evaluate the early efficacy of chemotherapy in patients with advanced lung adenocarcinoma. MATERIAL AND METHODS: A total of 101 patients with advanced lung adenocarcinoma were enrolled. Patients were classified into a response group and non-response group according to RECIST 1.1 standard. All patients underwent chest CT examination before and after two cycles of chemotherapy. A total of 293 radiomics features were calculated. The features between response group and non-response group were compared before and after chemotherapy. The diagnostic efficacy was evaluated using the receiver operating characteristic curve. RESULTS: The six pre-chemotherapy radiomics features were selected, with area under the curve (AUC), sensitivity, and specificity at 0.720, 68.3%, and 69.0% in the training group and 0.573, 50.0%, and 76.9% in the test group, respectively. The eleven post-chemotherapy radiomics features were selected, with AUC, sensitivity, specificity at 0.789, 75.6%, and 75.9% in the training group and 0.718, 61.1%, and 76.9% in the test group, respectively. The prognostic value of △f8, △f16, %f8, and %f16 were higher than the other features with AUCs of 0.787, 0.837, 0.763, and 0.877, respectively. CONCLUSION: Radiomics is expected to provide more valuable information for evaluating the chemotherapy efficacy of lung adenocarcinoma.

Hemostasis functions are associated with hemorrhagic transformation in non-atrial fibrillation patients: a case-control study.

BACKGROUND: Hemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients. METHODS: We consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels. RESULTS: In this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268-9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455-0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346-2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032-1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047-1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients. CONCLUSIONS: Low PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.

Comparison of poststroke depression between acute ischemic and hemorrhagic stroke patients.

OBJECTIVES: Depression is the most common mental complication in stroke survivors with about one-third of patients suffering from poststroke depression (PSD). This was the first prospective study aimed to compare the prevalence of PSD and its symptoms between two cohorts of patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). METHODS: Both AIS and ICH patients were simultaneously enrolled in the study. Depression symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17) after a 1-month follow-up. Patients were diagnosed with PSD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition and the HAMD-17 (HAMD scores >7). RESULTS: The prevalence of PSD (42.3%) in the ICH group was significantly higher than that (22.9%) in the AIS group (p < 0.001). After adjustment for conventional confounding factors, the odds ratio of PSD was 2.65 (95% CI, 1.34-5.24, p = 0.005) for ICH compared to AIS. Depressive symptoms consisting of anxiety, loss of interest, insomnia, and fatigue were more frequent in patients with ICH than in AIS patients. CONCLUSIONS: PSD was more prevalent, and the risk was over twofold higher in patients with ICH than AIS.

Diffusion kurtosis imaging and tumour microstructure for monitoring response to radiotherapy in human nasopharyngeal carcinoma xenografts.

OBJECTIVE: To investigate the correlations and feasibility of diffusion kurtosis imaging (DKI) parameters and tumour histopathology after radiotherapy in human nasopharyngeal carcinoma (NPC) xenografts on nude mice. MATERIALS AND METHODS: Seventy-two nude mice were used for the construction of CNE-1 (radio-insensitive) and CNE-2 (radio-sensitive) NPC xenograft models, followed by fraction irradiation at different doses of X-ray. The nude mice were randomly divided into six groups in each cell line models according to the dose of X-ray they have received and with six mice in each group. DKI scan was performed after radiation. DKI parameters, tumour histopathology and AQP-1 biomarkers were detected. One-way ANOVA and Pearson's correlation analysis were used in statistical analysis. RESULTS: In CNE-1 and CNE-2 NPC xenografts, D values were increased (P < 0.01 and P < 0.001), while K values (P < 0.01 and P < 0.001) and tumour size (P < 0.001 and P < 0.001) were reduced during fraction irradiation. Additionally, cell density (CD) and AQP-1 expressions were decreased, and necrosis ratio (NR) was increased in CNE-2 xenografts after fraction irradiation (P < 0.001). The changes in D values were negatively correlated with tumour size (r = -0.856, P < 0.001), CD (r = -0.918, P < 0.001), AQP-1 mRNA (r = -0.856, P < 0.001) and protein (r = -0.381, P = 0.022) expressions while positively correlated with NR (r = 0.908, P < 0.001) in CNE-2 xenografts. The changes in K values were positively correlated with tumour size (r = 0.964, P < 0.001), CD (r = 0.888, P < 0.001), AQP-1 mRNA (r = 0.955, P < 0.001) and protein (r = 0.330, P = 0.049) expression levels while negatively correlated with NR (r = -0.930, P < 0.001). However, in CNE-1 xenografts, there were no correlation between DKI parameters and the expression of AQP-1. CONCLUSION: Changes in D and K parameters after fractional irradiation are closely related with NPC cellular and pathological characteristics, especially size reduction and necrosis induction. These parameters exhibit potential abilities of monitoring the response to fractional irradiation in radio-sensitive NPC xenografts.

Integrating dynamic contrast-enhanced magnetic resonance imaging and diffusion kurtosis imaging for neoadjuvant chemotherapy assessment of nasopharyngeal carcinoma.

BACKGROUND: Since neoadjuvant chemotherapy (NAC) has proven a benefit for locally advanced nasopharyngeal carcinoma (NPC), early response evaluation after chemotherapy is important to implement individualized therapy for NPC in the era of precision medicine. PURPOSE: To determine the combined and independent contribution between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) in the early monitoring of NAC response for NPC. STUDY TYPE: Prospective. POPULATION: Fifty-three locally advanced NPC patients. FIELD STRENGTH/SEQUENCE: Four examinations before and at 4, 20, and 40 days after NAC initiation were performed at 3T MRI including DCE-MRI and DKI (b values = 0, 500, 1000, 1500 s/mm2 ). ASSESSMENT: DCE-MRI parameters (Ktrans [the volume transfer constant of Gd-DTPA], kep [rate constant], νe [the extracellular volume fraction of the imaged tissue], and νp [the blood volume fraction]) and DKI parameters (Dapp [apparent diffusion for non-Gaussian distribution] and Kapp [apparent kurtosis coefficient]) were analyzed using dedicated software. STATISTICAL TESTS: MRI parameters and their corresponding changes were compared between responders and nonresponders after one or two NAC cycles treatment using independent-samples Student's t-test or Mann-Whitney U-test depending on the normality contribution test and then followed by logistic regression and receiver operating characteristic curve (ROC) analyses. RESULTS: The responder group (RG) patients presented significantly higher mean Ktrans and Dapp values at baseline and larger Δ K ( 0 - 4 ) trans , Δvp(0-4) , and ΔDapp(0-4) values after either one or two NAC cycles compared with the nonresponder group (NRG) patients (all P < 0.05). ROC analyses demonstrated the higher diagnostic accuracy of combined DCE-MRI and DKI model to distinguish nonresponders from responders after two NAC cycles than using DCE-MRI (0.987 vs. 0.872, P = 0.033) or DKI (0.987 vs. 0.898, P = 0.047) alone. DATA CONCLUSION: Combined DCE-MRI and DKI models had higher diagnostic accuracy for NAC assessment compared with either model used independently. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1208-1216.

Metabolic profiling of normal hepatocyte and hepatocellular carcinoma cells via 1 H nuclear magnetic resonance spectroscopy.

Hepatocellular carcinoma (HCC) causes death mainly by disseminated metastasis progression from the organ being confined. Different metastatic stages are closely related to cellular metabolic profiles. Normal hepatocyte and HepG2 cell line from low metastatic HCC were studied by NMR-based metabolomic techniques. Multivariate and univariate statistical analyses were utilized to identify characteristic metabolites from cells and cultured media. Elevated levels of acetate, creatine, isoleucine, leucine, and phenylalanine were observed in HepG2 cells, suggesting more active in gathering nutrient components along with altered amino acid metabolisms and enhanced lipid metabolism. High glucose consumption was significantly different in low metastatic cells. A series of characteristic metabolites were identified and served as biomarkers. Relative metabolic pathway analysis shows that low metastatic HepG2 cell line exhibits active behaviors in metabolisms and biosynthesis of specific amino acids and energy metabolism. Moreover, characteristic metabolites-based classification models executed by support vector machines algorithm perform robustly to classify normal hepatocyte and HepG2 cell line. It is concluded that NMR-based metabolomic analyses of cell lines can provide a powerful approach to understand metastasis-related biological alterations. The present study also provides a basis for metabolic markers determination of hepatic carcinoma in the future clinical study.

Current advances in the development of natural meniscus scaffolds: innovative approaches to decellularization and recellularization.

The increasing rate of injuries to the meniscus indicates the urgent need to develop effective repair strategies. Irreparably damaged menisci can be replaced and meniscus allografts represent the treatment of choice; however, they have several limitations, including availability and compatibility. Another approach is the use of artificial implants but their chondroprotective activities are still not proved clinically. In this situation, tissue engineering offers alternative natural decellularized extracellular matrix (ECM) scaffolds, which have shown biomechanical properties comparable to those of native menisci and are characterized by low immunogenicity and promising regenerative potential. In this article, we present an overview of meniscus decellularization methods and discuss their relative merits. In addition, we comparatively evaluate cell types used to repopulate decellularized scaffolds and analyze the biocompatibility of the existing experimental models. At present, acellular ECM hydrogels, as well as slices and powders, have been explored, which seems to be promising for partial meniscus regeneration. However, their inferior biomechanical properties (compressive and tensile stiffness) compared to natural menisci should be improved. Although an optimal decellularized meniscus scaffold still needs to be developed and thoroughly validated for its regenerative potential in vivo, we believe that decellularized ECM scaffolds are the future biomaterials for successful structural and functional replacement of menisci.

Bifidobacterium adolescentis protects against necrotizing enterocolitis and upregulates TOLLIP and SIGIRR in premature neonatal rats.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disorder that is often seen in premature infants. Probiotics decrease the risk of NEC; however, the mechanism by which probiotics work is not clear. The goal of this study was to evaluate the preventive effect of Bifidobacterium adolescentis in an NEC rat model. METHODS: Sprague-Dawley neonatal rats were obtained by caesarean section after 20-21 d gestation and randomly divided into the following 3 groups: dam fed (DF), formula fed (FF), and formula + B. adolescentis (FB). Those in the FF and FB groups developed NEC after exposure to asphyxia and cold stress. All rats were sacrificed 72 h after birth and intestinal injury and mRNA expression of TLR4, TOLLIP and SIGIRR were assessed. RESULTS: B. adolescentis significantly increased the 72-h survival rate from 56.3% in the FF group to 86.7% in the FB group. B. adolescentis significantly reduced the histological score from a median of 3.0 in the FF group to a median of 1.0 in the FB group,and significantly decreased the rate of NEC-like intestinal injury from 77.8% in the FF group to 23.1% in the FB group. The mRNA expression of TLR4 increased 3.6 fold in the FF group but decreased by 2 fold from B. adolescentis treatment. mRNA expression of TOLLIP and SIGIRR decreased 4.3 and 3.7 fold, respectively, in the FF group. B. adolescentis significantly increased mRNA expression of TOLLIP and SIGIRR by 3.7 fold and 2.6 fold, respectively. CONCLUSIONS: This study demonstrated B. adolescentis prevents NEC in preterm neonatal rats and that the mechanism for this action might be associated with the alteration of TLR4, TOLLIP, and SIGIRR expression.

Impact of preeclampsia on megakaryocytopoesis and platelet homeostasis of preterm infants.

UNLABELLED: The aim of this article is to investigate the megakaryopoyesis and thrombopoiesis in preterm infants born to mothers with preeclampsia and the potential effects mediated by soluble fms-like tyrosine kinase 1 (sFlt1) and thrombopoietin (TPO). A perspective case-control study was performed on 26 cord blood of preterm newborns born to mothers with preeclampsia (PE group) and 26 of preterms born to mothers without preeclampsia (control group). Circulating megakaryocyte count and megakaryocyte colony forming units (CFU-MK) were quantified by whole blood infiltration method and plasma clot culture system, respectively. Platelet activation markers, CD62P and CD63, were estimated by flow cytometry. Immunosorbent assays (ELISA) were employed to estimate plasma levels of sFlt1 and TPO of the two groups. When compared to the controls, infants born to mothers with PE had significantly lower peripheral platelet count (PE vs. CONTROLS: 157.9 [44.6] vs. 239.6 [57.5] × 10(9)/l, p < 0.001), circulating MK count (5.8 [1.0] vs. 7.7 [0.9]/ml, p < 0.001) and CFU-MK (14.1 [2.1] vs. 20.1 [2.8]/1 × 10(5) cell, p < 0.001); greater expressions of CD62P (15.5 [2.3] vs. 11.4 [1.9]% platelets, p < 0.001) and CD63 (12.3 [2.4] vs. 9.0 [1.6]% platelets, p < 0.001); increased plasma Flt level (130.1 [8.0] vs. 97.7 [8.7] pg/ml, p < 0.001) and TPO level (129.5 [17.8] vs. 98.9 [11.8] pg/ml, p < 0.001). In PE group, sFlt instead of TPO showed a significantly negative relationship with platelet counts, CFU-MK and circulating MK count, a positive relationship with CD62P, CD63 expressions. In control group, both sFlt and TPO did not show any relationship with these parameters. sFlt played important role in megakaryocytopoesis and platelet homeostasis in preterm infants born to mothers with PE. Its mechanism maybe the effect of impaired megakaryocyte formation and increased platelet activation.

Early response to chemoradiotherapy for nasopharyngeal carcinoma treatment: Value of dynamic contrast-enhanced 3.0 T MRI.

PURPOSE: To prospectively evaluate the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) value for predicting early nasopharyngeal carcinoma (NPC) chemoradiotherapy (CRT) response. MATERIALS AND METHODS: Forty-two patients with advanced NPC were recruited and received three DCE-MRI exams before treatment (Pre-Tx), as well as 3 days (Day 3-Tx) and 40 days (Day 40-Tx) after chemotherapy initiation (two neoadjuvant chemotherapy cycles, NAC). We used DCE-Tool to measure primary tumor kinetic parameters (K(trans) , Kep , ve , and vp ) using the extended Tofts model. Kinetic parameters and corresponding changes were compared between responders and nonresponders after NAC or CRT treatment using Student's t or Mann-Whitney U tests. RESULTS: Response to two NAC cycles correlated with short-term local control (P = 0.01). Compared to the nonresponder group, the responder group presented with significantly larger ΔK(trans) (0-3) , ΔKep(0-3) , and Δvp(0-3) values after NAC (P < 0.05). The complete response group after CRT exhibited significantly lower K(trans) (Day 40-Tx) and larger ΔK(trans) (0-3) values than the residual group (P = 0.05). High sensitivity (range: 74.1%-90%) and moderate-to-high specificity (range: 50%-84.3%) distinguished nonresponders from responders grouping after NAC or CRT, with diagnostic efficiency ranging from 69.3%-88%. CONCLUSION: Our study showed kinetic parameter changes earlier after chemotherapy were potential markers for NPC patients receiving CRT therapy following NAC.

Diffusion kurtosis imaging predicts neoadjuvant chemotherapy responses within 4 days in advanced nasopharyngeal carcinoma patients.

PURPOSE: To explore the clinical value of diffusion kurtosis imaging (DKI) and monoexponential diffusion-weighted imaging (DWI) for predicting early response to neoadjuvant chemotherapy (NAC) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-nine patients with stage III-IVb NPC underwent four 3.0T MR scans: prior to, and on the 4th, 21st, 42nd days after NAC initiation. The parameters of DKI (corrected diffusion coefficient, D; excess diffusion kurtosis coefficient, K) and monoexponential DWI (apparent diffusion coefficient, ADC) were obtained at the first three scans. Statistical methods included Student's t-test or Mann-Whitney U-test, receiver operating characteristic (ROC) curve analyses and paired X(2) test. RESULTS: D(pre) in responders group (RG) was significantly lower than nonresponders group (NRG) (1.029 ± 0.033 vs. 1.184 ± 0.055, ×10(-3) mm(2) /s, P = 0.020). ADC(day4) and ΔD(day4) were the most useful parameters of the two diffusional models to distinguish RG from NRG, respectively (area under the curve, 0.761 vs. 0.895). ΔD(day4) was more sensitive than ADC(day4) to predict treatment response to NAC (P = 0.006). CONCLUSION: Both DKI and monoexponential DWI showed potential to predict treatment response to NAC prior to morphological change. DKI may be superior to monoexponential DWI for predicting early response to NAC in patients with locally advanced NPC.

Dynamic contrast-enhanced MRI of nasopharyngeal carcinoma: a preliminary study of the correlations between quantitative parameters and clinical stage.

PURPOSE: To evaluate the relationship between quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical stage of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-one newly diagnosed NPC patients received MRI examination on Philips Achieva 3.0 Tesla TX MR system. We used DCE-Tool (Philips Healthcare, Best, The Netherlands) to investigate parameters from primary tumors. Tumor/node/metastasis and corresponding clinical stages were determined based on 2009 UICC 7th edition. The correlations between quantitative parameters and clinical stage were correlated using Pearson correlation analysis. RESULTS: Mean K(trans) , Kep , ve , and vp for primary tumors were 0.500 ± 0.188/min, 0.744 ± 0.273/min, 0.986 ± 0.595, and 0.052 ± 0.071, respectively. Both K(trans) and Kep of tumors showed moderate negative correlation with clinical stage, T stage and N stage (P < 0.05), while ve showed moderate positive correlation with them (P < 0.05). vp revealed a moderate negative correlation with T stage (r = -0.369; P < 0.004). Kep and ve have significant differences between many early and advanced stages patients. CONCLUSION: DCE-MRI is feasible to assess vascular permeability of NPC patients. Our results first revealed that the quantitative parameters were significantly related to clinical stage of NPC. Thus, DCE-MRI may be valuable to add noninvasive prognostic indicators in evaluating NPC.

The application value of LAVA-flex sequences in enhanced MRI scans of nasopharyngeal carcinoma: comparison with T1WI-IDEAL.

Introduction: Magnetic resonance imaging (MRI) staging scans are critical for the diagnosis and treatment of patients with nasopharyngeal cancer (NPC). We aimed to evaluate the application value of LAVA-Flex and T1WI-IDEAL sequences in MRI staging scans. Methods: Eighty-four newly diagnosed NPC patients underwent both LAVA-Flex and T1WI-IDEAL sequences during MRI examinations. Two radiologists independently scored the acquisitions of image quality, fat suppression quality, artifacts, vascular and nerve display. The obtained scores were compared using the Wilcoxon signed rank test. According to the signal intensity (SI) measurements, the uniformity of fat suppression, contrast between tumor lesions and subcutaneous fat tissue, and signal-to-noise ratio (SNR) were compared by the paired t-test. Results: Compared to the T1WI-IDEAL sequence, LAVA-Flex exhibited fewer artifacts (P<0.05), better visualization of nerves and vessels (P<0.05), and performed superior in the fat contrast ratio of the primary lesion and metastatic lymph nodes (0.80 vs. 0.52, 0.81 vs. 0.56, separately, P<0.001). There was no statistically significant difference in overall image quality, tumor signal-to-noise ratio (SNR), muscle SNR, and the detection rate of lesions between the two sequences (P>0.05). T1WI-IDEAL was superior to LAVA-Flex in the evaluation of fat suppression uniformity (P<0.05). Discussion: LAVA-Flex sequence provides satisfactory image quality and better visualization of nerves and vessels for NPC with shorter scanning times.

Early assessment of induction chemotherapy response of nasopharyngeal carcinoma by pretreatment diffusion-weighted magnetic resonance imaging.

OBJECTIVES: This study aimed to evaluate the feasibility of pretreatment diffusion-weighted imaging in predicting response after induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC). METHODS: Fifty-four patients with stage III and IV NPC underwent MRI examination at baseline, after 2 cycles of chemotherapy, and at the end of chemoradiotherapy. Apparent diffusion coefficient (ADC) values were compared between effective and ineffective subjects after IC. RESULTS: Mean ADC in effective groups was significantly (P < 0.05) higher than that in the ineffective group. Average and minimum ADCs demonstrated higher sensitivity than maximum ADC for predicting IC response, with 68.4%, 71.1%, and 50.0%, respectively, at an equivalent 68.7% specificity. We observed negative correlations between pretreatment ADC and tumor regression after chemotherapy (γ = - 0.425, P = 0.001) and after chemoradiotherapy (γ = - 0.418, P = 0.003). CONCLUSIONS: Pretreatment ADC was a valuable biomarker for predicting IC response of NPC. Noninvasive diffusion-weighted imaging provides additional indicator in guiding optical therapeutic options for patients with NPC.

[Low-dose daily de-escalatory administration of tadalafil for psychological erectile dysfunction].

OBJECTIVE: To investigate the effect of low-dose daily de-escalatory administration of tadalafil on psychological erectile dysfunction (ED). METHODS: We randomized 84 psychological ED patients into an observation and a control group of equal number to receive low-dose daily de-escalatory administration and on-demand medication of tadalafil, respectively, both for 2 months. We compared the scores on IIEF-5 and erection hardness (EHS) between the two groups before and after the treatment. RESULTS: The treatment and follow-up were accomplished for 79 cases, with 5 withdrawals in the control group. The IIEF-5 and EHS scores were remarkably improved in both the observation and control groups after treatment. The rate of therapeutic effectiveness was significantly higher in the observation group than in the control (95.2% vs 86.5%, P < 0.05). CONCLUSION: Low-dose daily de-escalatory administration of tadalafil is highly effective and even better than on-demand medication of tadalafil for psychological ED.

MRI-based deep learning model predicts distant metastasis and chemotherapy benefit in stage II nasopharyngeal carcinoma.

Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.

Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat.

BACKGROUND: Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses. RESULTS: We used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group. CONCLUSIONS: Our data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.

Microbial Community Structure of Colostrum in Women with Antibiotic Exposure Immediately After Delivery.

Background: The microbial community in human milk is associated with many maternal and neonatal factors. This study aimed to investigate the effect of antibiotic exposure on the microbial community structure of colostrum. Methods: Twenty women with antibiotic treatment immediately after delivery and 10 age-matched control women were enrolled at the Guangdong Women and Children Hospital. Colostrum samples were collected within postpartum 30 hours. The V4 variable region of the bacterial 16S rRNA gene was sequenced to characterize the microbial profile using Illumina MiSeq platform. Results: Phyla Proteobacteria and Firmicutes were the predominant bacteria in colostrum samples. The core and abundant genera in colostrum included Streptococcus, Staphylococcus, and Pseudomonas. Compared with the control group, principal coordinate analysis based on the Bray-Curtis distance showed a significant difference in milk microbial community in women with antibiotic exposure, accompanied by a significantly lower alpha diversity and a different microbial ecological network. Furthermore, the relative abundances of genera Actinomyces, Anaerobacter, and Clostridium_sensu_stricto significantly decreased after antibiotic treatment. Conclusions: This study provided evidence of alterations in the colostrum microbial community with antibiotic exposure, improving our understanding of the effects of antibiotic treatment on the milk microbiome.

Bone mesenchymal stem cell-derived exosomes prevent hyperoxia-induced apoptosis of primary type II alveolar epithelial cells in vitro.

Background: The presence of alveolar epithelial type II cells (AECIIs) is one of the most important causes of bronchopulmonary dysplasia (BPD). Exosomes from bone mesenchymal stem cells (BMSCs) can reduce hyperoxia-induced damage and provide better results in terms of alveolar and pulmonary vascularization parameters than BMSCs. Currently, intervention studies using BMSC-derived exosomes on the signaling pathways regulating proliferation and apoptosis of alveolar epithelial cells under the condition of BPD have not been reported. This study investigated the effects of rat BMSC-derived exosomes on the proliferation and apoptosis of hyperoxia-induced primary AECIIs in vitro. Methods: The isolated AECIIs were grouped as follows: normal control (21% oxygen), hyperoxia (85% oxygen), hyperoxia+exosome (20 µg/mL), hyperoxia+exosome+LY294002 (PI3K/Akt inhibitor, 20 µM), and hyperoxia+exosome+rapamycin (mTOR inhibitor, 5 nM). We used the PI3K/Akt inhibitor LY294002 and the mTOR inhibitor rapamycin to determine the roles of the PI3K/Akt and mTOR signaling pathways. The effects of BMSC-derived exosomes on AECII proliferation and apoptosis were assessed, respectively. Results: Decreased levels of the antiapoptotic protein Bcl-2, the cell proliferation protein Ki67, p-PI3K, p-Akt, and p-mTOR, as well as increased levels of AECII apoptosis and the proapoptotic protein Bax in the hyperoxia group were observed. Notably, Sprague Dawley rat BMSC-derived exosomes could reverse the effect of hyperoxia on AECII proliferation. However, the application of LY294002 and rapamycin inhibited the protective effects of BMSC-derived exosomes. Conclusion: Our findings revealed that BMSC-derived exosomes could regulate the expression of apoptosis-related proteins likely via the PI3K/Akt/mTOR signaling pathway, thereby preventing hyperoxia-induced AECII apoptosis.

Application Value of Magnetic Resonance Radiomics and Clinical Nomograms in Evaluating the Sensitivity of Neoadjuvant Chemotherapy for Nasopharyngeal Carcinoma.

OBJECTIVE: To predict the sensitivity of nasopharyngeal carcinoma (NPC) to neoadjuvant chemotherapy (NACT) based on magnetic resonance (MR) radiomics and clinical nomograms prior to NACT. MATERIALS AND METHODS: From January 2014 to July 2015, 284 consecutive patients with pathologically confirmed NPC underwent 3.0 T MR imaging (MRI) before initiating NACT. The patients' data were randomly assigned to a training set (n = 200) or a test set (n = 84) at a ratio of 7:3. The clinical data included sex, tumor (T) stage, lymph node (N) stage, American Joint Committee on Cancer (AJCC) stage, and the plasma concentration of Epstein-Barr virus (EBV) DNA. The regions of interest (ROI) were manually segmented on the axial T2-weighted imaging (T2WI) and enhanced T1-weighted imaging (T1WI) sequences using ITK-SNAP software. The radiomics data were post-processed using AK software. Moreover, the Maximum Relevance Minimum Redundancy (mRMR) algorithm and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for dimensionality reduction to screen for the features that best predicted the treatment efficacy, and clinical risk factors were used in combination with radiomics scores (Rad-scores) to construct the clinical radiomics-based nomogram. DeLong's test was utilized to compare the area under the curve (AUC) values of the clinical radiomics-based nomogram, radiomics model, and clinical nomogram. Decision curve analysis (DCA) was employed to evaluate each model's net benefit. RESULTS: The clinical nomogram was constructed based on data from patients who were randomly assigned according to T2WI and enhanced T1WI sequences. In the training set, the T2WI sequence-based clinical radiomics nomogram and the radiomics model outperformed the clinical nomogram in predicting the NACT efficacy (AUC, 0.81 vs. 0.60, p = 0.001279 and 0.76 vs. 0.60, p = 0.03026). These findings were well-verified in the test set. The enhanced T1WI sequence-based clinical radiomics nomogram exhibited better performance in predicting treatment efficacy than the clinical nomogram (AUC, 0.79 vs. 0.62, respectively; p = 0.0000834). The DCA revealed that the T2WI and clinical radiomics-based nomograms resulted in a net benefit in predicting the NACT efficacy. CONCLUSION: The clinical radiomics-based nomogram improved the prediction of NACT efficacy, with the T2WI sequence-based clinical radiomics achieving the best effect.