The reproducibility and predictivity of radiomic features extracted from dynamic contrast-enhanced computed tomography of hepatocellular carcinoma.

PURPOSE: To assess the reproducibility of radiomic features (RFs) extracted from dynamic contrast-enhanced computed tomography (DCE-CT) scans of patients diagnosed with hepatocellular carcinoma (HCC) with regards to inter-observer variability and acquisition timing after contrast injection. The predictive ability of reproducible RFs for differentiating between the degrees of HCC differentiation is also investigated. METHODS: We analyzed a set of DCE-CT scans of 39 patients diagnosed with HCC. Two radiologists independently segmented the scans, and RFs were extracted from each sequence of the DCE-CT scans. The same lesion was segmented across the DCE-CT sequences of each patient's scan. From each lesion, 127 commonly used RFs were extracted. The reproducibility of RFs was assessed with regard to (i) inter-observer variability, by evaluating the reproducibility of RFs between the two radiologists; and (ii) timing of acquisition following contrast injection (inter- and intra-imaging phase). The reproducibility of RFs was assessed using the concordance correlation coefficient (CCC), with a cut-off value of 0.90. Reproducible RFs were used for building XGBoost classification models for the differentiation of HCC differentiation. RESULTS: Inter-observer analyses across the different contrast-enhancement phases showed that the number of reproducible RFs was 29 (22.8%), 52 (40.9%), and 36 (28.3%) for the non-contrast enhanced, late arterial, and portal venous phases, respectively. Intra- and inter-sequence analyses revealed that the number of reproducible RFs ranged between 1 (0.8%) and 47 (37%), inversely related with time interval between the sequences. XGBoost algorithms built using reproducible RFs in each phase were found to be high predictive ability of the degree of HCC tumor differentiation. CONCLUSIONS: The reproducibility of many RFs was significantly impacted by inter-observer variability, and a larger number of RFs were impacted by the difference in the time of acquisition after contrast injection. Our findings highlight the need for quality assessment to ensure that scans are analyzed in the same physiologic imaging phase in quantitative imaging studies, or that phase-wide reproducible RFs are selected. Overall, the study emphasizes the importance of reproducibility and quality control when using RFs as biomarkers for clinical applications.

The value of phenylalanine in predicting atrial fibrillation risk in chronic heart failure.

Backgrounds: Atrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF. Methods: The cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography-tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months). Results: Serum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P < 0.001). Serum Phe value was the independent risk factor for predicting AF in HF [odds ratio (OR), 1.640; 95% CI: 1.150-2.339; P = 0.006]. Phe levels were correlated positively with hsCRP value in HF patients with AF (r = 0.577, P < 0.001). The elevated Phe levels were associated with a higher risk of HF endpoint events in HF patients with AF (log-rank P = 0.005). Conclusions: In HF with AF subjects, elevated Phe value confers an increased risk for prediction AF and was more related to poor HF endpoint events. Phe can be a valuable index of AF in HF.

Clinical spectrum and possible pathogenesis of progressive outer retinal necrosis.

OBJECTIVE: Progressive outer retinal necrosis (PORN) is an alphaherpesvirus-caused panuveitis with devastating consequences for the eye. Our study aims to describe new findings in the clinical spectrum and propose a mechanism for the pathogenesis of PORN. METHODS: Observational, consecutive case series. Seven eyes from five patients diagnosed with PORN were enrolled. Detailed case histories, ocular examination findings and multimodal images of retina were collected. Optic nerve and brain imaging were obtained by MRI. RESULTS: All eyes were confirmed human alphaherpesviruses positive in ocular fluid by qPCR. Optic nerve oedema was observed on MRI in all eyes. A relative afferent pupillary defect was recorded in the affected eye for the unilateral cases. Two patients with unilateral involvement had a history of viral encephalitis and focal encephalomalacia found in the temporal lobe on brain MRI. The affected eyes were characterised by sensory retinal necrosis sparing retinal pigment epithelium, starting at the end of the retinal nerve fibre (horizontal raphe or peripheral area of the retina) and progressing rapidly along the nerve fibre. The wall of the retinal artery and vein was destroyed, resulting in blood flow interruption on fluorescein angiography and retinal haemorrhages along the large vessels. CONCLUSIONS: Combination the neurotropic characteristics of alphaherpesviruses and the signs of PORN, we hypothesised that the reactivated PORN virus originated from the lateral geniculate nucleus, then propagated along the optic nerve and was released at the terminals, causing necrosis of the entire sensory retina rather than just affecting the outer segment.

Development of Ampelopsis Radix Ethanolic Extract Loaded Phytosomes for Improved Efficacy in Colorectal Cancer: in vitro and in vivo Assessment Study.

The aim of present work was to develop and evaluate Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer. Ampelopsis Radix ethanolic extract was prepared by Soxhlet extraction process followed by development of phytosomes using lipids and other excipients. The phytosomes were evaluated for surface morphology, particle size analysis, zeta potential, encapsulation efficiency, drug loading, in vitro drug release, Cytotoxicity assay, cellular uptake studies were performed on HCT-116 and SW480 cell lines. In vivo antitumor activity was performed. The phytosomes were found spherical shape with smooth surface characteristics. The drug loading was observed between 29.27 to 42.10 % while particle size of 85 to 130 nm was found. Phytosomes showed desired release pattern which is required for cancer treatment. Phytosomes showed maximum antiproliferative activity on cell lines over the period of 24 hours and showed highest internalization within both types of cell lines. The survival rate of animals in phytosomes treated group was found to be 100% proving the safety and efficacy. Phytosomes showed highest antitumor activity as compared to other formulations. Study confirms the potential use Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer.

Efficiency and safety of continuous theta burst stimulation for primary insomnia: A randomized clinical trial.

OBJECTIVES: Primary insomnia is a substantial public health burden, but current treatments for this disorder have limited effectiveness and adherence. Herein, we aimed to investigate the efficacy and safety of continuous theta burst stimulation (cTBS) for the treatment of primary insomnia. METHODS: This two-armed, randomized, sham-controlled trial was conducted at Peking University Sixth Hospital and local community clinics. A total of 46 patients with primary insomnia were recruited and randomly allocated to either the cTBS group or sham group. Forty-one patients completed 10 sessions of cTBS or sham intervention and follow-up assessments. RESULTS: After the intervention, the severity of insomnia was significantly lower in the cTBS group than in the sham group, with a large effect size (Cohen's d = -1.938). Additionally, 52.4 % of patients in the cTBS group achieved a response (Insomnia Severity Index score reduction ≥8), whereas only 4 % of patients in the sham group achieved a response. The duration of objective total sleep time and slow-wave sleep were higher in the cTBS group than in the sham group. The degree of anxiety was lower in the cTBS group than in the sham group. There were no significant differences in depression, sleepiness, or cognitive function between the cTBS and sham groups. During follow-up, the sleep quality of the cTBS group significantly improved and remained stable at the 6-month follow-up. CONCLUSION: In this randomized clinical trial, cTBS improved insomnia symptoms and was generally well tolerated, thus supporting the further development of cTBS for the treatment of primary insomnia.

Incorporation of amylose improves rheological and textural properties of Moringa oleifera seed salt-soluble protein.

The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.

Coronary angiography in dextrocardia with situs inversus and acute myocardial infarction: A case report and literature review.

We present the case of a 74-year-old man with dextrocardia and situs inversus who presented with non-ST-elevation acute myocardial infarction. The patient underwent successful coronary angiography without requiring percutaneous coronary intervention or coronary artery bypass grafting. We discuss the patient's clinical characteristics, electrocardiography findings, diagnosis, and treatment, and review the relevant literature.

Memory Reconsolidation Updating in Substance Addiction: Applications, Mechanisms, and Future Prospects for Clinical Therapeutics.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.

Age-related alterations in vortex veins on indocyanine green angiography.

To determine age-related alterations in vortex veins in healthy subjects. A total of 228 healthy subjects (aged 4 to 86 years) were recruited and divided into four groups (G1, <21 years; G2, 21-40 years; G3, 41-60 years; and G4, 61-86 years). The clinical characteristics of the participants were recorded, and parameters including the number of vortex vein roots (NVVR), the central vortex vein diameter (CVVD), the mean root area of the vortex vein (MRAVV), and the weighted mean of the thickest branch diameter (WMTBD) were obtained by marking the vortex veins on indocyanine green angiography (ICGA). The NVVR in the age group over 60 years old was significantly lower than that in other age groups (P < 0.05). The CVVD, MRAVV, and WMTBD of all age groups increased with increasing age (P < 0.05). The NVVR was unevenly distributed among the quadrants (P < 0.001). The proportions of type four vortex veins (complete systems including ampulla) and anastomotic branches of the vortex veins were significantly increased in elderly participants over 50 years of age (P < 0.05). Subfoveal choroidal thickness was significantly correlated with age, NVVR, CVVD and MRAVV (P < 0.05). This is the first study to reveal age-related alterations in vortex veins on ICGA in a healthy population. Aging may lead to partial vortex occlusion and residual vortex dilation. As age increases, anastomotic branches increasingly appear between the originally independent vortex veins. Translational relevance: Aging may lead to partial vortex occlusion and residual vortex dilation.

Predicting neurodevelopmental outcomes in extremely preterm neonates with low-grade germinal matrix-intraventricular hemorrhage using synthetic MRI.

Objectives: This study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions. Materials and methods: In this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling. Results: Elevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p < 0.05). The T1-FWM, T1-Caudate, T2-FWM, and T2-Caudate models exhibited overall predictive performance with AUC values of 0.751, 0.695, 0.856, and 0.872, respectively. Combining these models into T1-FWM + T1-Caudate + T2-FWM + T2-Caudate resulted in an improved AUC of 0.955, surpassing individual models (p < 0.05). Bootstrap resampling confirmed the validity of the models. Conclusion: Synthetic MRI proves effective in early predicting adverse outcomes in extremely preterm infants with GMH-IVH. The combination of T1-FWM + T1-Caudate + T2-FWM + T2-Caudate further enhances predictive accuracy, offering valuable insights for early intervention strategies.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Association of lifestyle with sleep health in general population in China: a cross-sectional study.

The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Integrated single-cell and bulk RNA sequencing analyses identify an immunotherapy nonresponse-related fibroblast signature in gastric cancer.

Factors that determine nonresponse to immune checkpoint inhibitor (ICI) remain unclear. The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for cancer treatment. There is, however, a lack of CAF-related signature in predicting response to immunotherapy in gastric cancer (GC). Single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data of GC immunotherapy were downloaded from the Gene Expression Omnibus database. Bulk RNA-seq data were obtained from The Cancer Genome Atlas. The R package 'Seurat' was used for scRNA-seq data processing. Cellular infiltration, receptor-ligand interactions, and evolutionary trajectory analysis were further explored. Differentially expressed genes affecting overall survival were obtained using the limma package. Weighted Gene Correlation Network Analysis was used to identify key modules of immunotherapy nonresponder. Prognostic model was constructed by univariate Cox and least absolute contraction and selection operator analysis using the intersection of activated fibroblast genes (AFGs) with key module genes. The differences in clinicopathological features, immune microenvironment, immunotherapy prediction, and sensitivity to small molecule agents between the high- and low-risk groups were further investigated. Based on scRNA-seq, we finally identified 20 AFGs associations with the prognosis of GC patients. AFGs' high expression levels were correlated with both poor prognosis and tumor progression. Three genes (FRZB, SPARC, and FKBP10) were identified as immunotherapy nonresponse-related fibroblast genes and used to construct the prognostic signature. This signature is an independent significant risk factor affecting the clinical outcomes of GC patients. Remarkably, there were more CD4 memory T cells, resting mast cells, and M2 macrophages infiltrating in the high-risk group, which was characterized by higher tumor immune exclusion. Moreover, patients with higher risk scores were more prone to not respond to immunotherapy but were more sensitive to various small molecule agents, such as memantine. In conclusion, this study constructed a fibroblast-associated ICI nonresponse gene signature, which could predict the response to immunotherapy. This study potentially revealed a novel way to overcome immune resistance in GC.

Hippocampal, thalamic, and amygdala subfield morphology in major depressive disorder: an ultra-high resolution MRI study at 7-Tesla.

Morphological changes in the hippocampal, thalamic, and amygdala subfields have been suggested to form part of the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented in-depth examinations at the subfield level, precluding a fine-grained understanding of these subfields and their involvement in MDD pathophysiology. We uniquely employed ultra-high field MRI at 7.0 Tesla to map hippocampal, thalamic, and amygdala subfields in MDD. Fifty-six MDD patients and 14 healthy controls (HCs) were enrolled in the final analysis. FreeSurfer protocols were used to segment hippocampal, thalamic, and amygdala subfields. Bayesian analysis was then implemented to assess differences between groups and relations with clinical features. While no effect was found for MDD diagnosis (i.e., case-control comparison), clinical characteristics of MDD patients were associated with subfield volumes of the hippocampus, thalamus, and amygdala. Specifically, the severity of depressive symptoms, insomnia, and childhood trauma in MDD patients related to lower thalamic subfield volumes. In addition, MDD patients with typical MDD versus those with atypical MDD showed lower hippocampal, thalamic, and amygdala subfield volumes. MDD patients with recurrent MDD versus those with first-episode MDD also showed lower thalamic subfield volumes. These findings allow uniquely fine-grained insights into hippocampal, thalamic, and amygdala subfield morphology in MDD, linking some of them to the clinical manifestation of MDD.

VISION AND METAMORPHOPSIA OUTCOMES OF MACULAR BUCKLING FOR FOVEOSCHISIS-ASSOCIATED MACULAR DETACHMENT IN HIGHLY MYOPIC EYES.

PURPOSE: To assess the functional outcomes in visual acuity, metamorphopsia, and vision-related quality of life (VR-QOL) and to evaluate prognostic factors after macular buckling (MB) surgery in eyes with high myopia and foveoschisis (FS)-associated macular detachment (MD). METHODS: Thirty-nine eyes of 39 patients with FS-associated MD who underwent MB surgery were enrolled. Measured outcomes comprised best-corrected visual acuity (BCVA), metamorphopsia, VR-QOL, axial length (AL), macular reattachment, and resolution of foveoschisis. In addition, factors affecting final BCVA and metamorphopsia were analyzed. RESULTS: At 12 months postoperatively, 36 eyes (92.31%) achieved macular reattachment, 37 eyes (94.87%) achieved complete resolution of foveoschisis, and metamorphopsia diminished in 31 eyes (79.49%). LogMAR BCVAs at baseline and months 1, 3, 6, and 12 postoperatively were 0.62 ± 0.35 (20/83), 0.65 ± 0.3 (20/89), 0.59 ± 0.31 (20/77), 0.54 ± 0.31 (20/69), and 0.46 ± 0.27 (20/57) (P < 0.001), respectively. Metamorphopsia scores by M-CHARTS were 1.36° ± 0.51°, 1.04° ± 0.51°, 0.74° ± 0.47°, 0.59° ± 0.47°, and 0.13° ± 0.29° (P < 0.001). All Visual Function Questionnaire-25 subscales demonstrated significant improvement postoperatively, with the exception of "general health" (P = 0.08) and "driving" (P = 0.111). Preoperative BCVA was an independent risk factor for postoperative BCVA at month 12 (r = 0.638, P < 0.001), and the preoperative M-score was an independent risk factor for postoperative M-score at month 12 (r = 0.187, P = 0.045). CONCLUSION: MB surgery significantly improved BCVA, metamorphopsia, and VR-QOL in patients with FS-associated MD. Preoperative BCVA and metamorphopsia score were prognostic factors for postoperative BCVA and metamorphopsia score at month 12.

To nap or not? Evidence from a meta-analysis of cohort studies of habitual daytime napping and health outcomes.

Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less.

Differentiating lung neuroendocrine neoplasms from tumor-like infection using CT in patients with ectopic ACTH syndrome.

OBJECTIVES: Pulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators. METHODS: Forty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected. RESULTS: High-sensitivity C-reactive protein (p < 0.001) and expectoration occurrence (p = 0.04) were higher, and finger oxygen saturation (p = 0.01) was lower in the infection group than the NENs group. Higher-grade NENs were underrepresented in our cohort. Pulmonary NENs were solitary primary tumors, 80% of which were peripheral tumors. Overlying vessel sign and airway involvement were more frequent in the NENs group (p < 0.001). Multifocal (p = 0.001) and peripheral (p = 0.02) lesions, cavity (p < 0.001), spiculation (p = 0.01), pleural retraction (p < 0.001), connection to pulmonary veins (p = 0.02), and distal atelectasis or inflammatory exudation (p = 0.001) were more frequent in the infection group. The median CT value increment between the non-contrast and arterial phases was significantly higher in NENs lesions (p < 0.001). Receiver operating characteristic curve analysis indicated a moderate predictive ability at 48.3 HU of delta CT value (sensitivity, 95.0%; specificity, 54.1%). CONCLUSION: Chest CT scans are valuable for localizing and characterizing pulmonary lesions in rare EAS, thereby enabling prompt differential diagnosis and treatment. CRITICAL RELEVANCE STATEMENT: Thin-slice CT images are valuable for the localization and identification of pulmonary ectopic adrenocorticotropic hormone syndrome lesions, leading to prompt differential diagnosis and effective treatment. KEY POINTS: Lung tumor-like infections can mimic neuroendocrine neoplasms (NENs) in ectopic adrenocorticotropic hormone syndrome (EAS) patients. NENs are solitary lesions, whereas infections are multiple peripheral pseudotumors each with identifying imaging findings. Typical CT signs aid in localization and creating an appropriate differential diagnosis.

Diagnostic and prognostic value of CD44v9 and TIM3 expression in CK­ and CK+ regions in gastric cancer tissues.

The specificity and sensitivity of the current diagnostic and prognostic biomarkers for gastric cancer (GC) are limited. The present study aimed to evaluate the diagnostic and prognostic significance of cluster-of-differentiation gene 44 variant isoform 9 (CD44v9) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) expression levels alone or combined in the tumor tissues of patients with GC and reveal the roles of CD44v9 and TIM3 in the cytokeratin (CK)+ and CK- regions. Multiplex immunofluorescence staining was performed for CD44v9, TIM3 and CK using a tissue microarray. The tissues were divided into three regions based on CK expression: Total, CK+, and CK- regions. The diagnostic and prognostic value was evaluated using receiver operating characteristic curves, Kaplan-Meier and Cox regression analyses. The results demonstrated that the density of cells expressing CD44v9, TIM3 and co-expressing CD44v9 and TIM3 (CD44v9/TIM3) in both the CK+ and CK- regions of tumor tissues was significantly higher than those in normal tissues (P<0.001). Moreover, the expression of CD44v9 in the CK- region was significantly positively correlated with age and tumor grade (P<0.05), and the expression of CD44v9/TIM3 in the CK- region of tumor tissues was significantly positively correlated with age, tumor grade and metastasis (P<0.05). Furthermore, the area under the curve for TIM3 expression in the CK+ region was 0.709, with a sensitivity of 45.83% and a specificity of 85.54% (P<0.001). High expression of CD44v9 in the CK- region was also significantly associated with poor survival and independently predicted a poor prognosis in patients with GC (hazard ratio, 2.387; 95% confidence interval, 1.384-4.118; P<0.01). In conclusion, dividing tissue regions based on CK expression is important for the diagnosis of GC. The expression of TIM3 in the CK+ region demonstrated diagnostic potential for GC, and high expression of CD44v9 in the CK- region was an independent prognostic risk factor for patients with GC.

Gender differences in major depressive disorder at different ages: a REST-meta-MDD project-based study.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous disease, with differences in clinical manifestations among depression patients based on onset ages and genders. The neural mechanisms underlying these differences remain unclear. In this study, we utilized resting state functional imaging data from a large sample database and adopted the ReHo method to investigate gender differences in local brain function in MDD patients across different onset age groups. METHODS: The study included 364 MDD patients and 695 healthy participants who were part of the REST-meta-MDD project. Regional homogeneity (ReHo) assessed gender disparities in MDD and healthy individuals within groups delineated by gender and onset age (young group: 18-29 years; middle-aged group: 30-45 years). RESULTS: Among the young MDD groups, there were significant gender differences in the right superior frontal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and right superior parietal lobule, with male MDD patients having higher ReHo values compared to females. When compared to healthy males, male MDD patients exhibited elevated ReHo values in the right superior parietal lobule. In the middle-aged groups, a marked ReHo difference was observed in the bilateral cerebellum posterior lobe, with female MDD patients showing higher ReHo values. CONCLUSIONS: The functional mechanisms of MDD differ between genders and show distinct variations across different onset age groups. These findings underscore the importance of developing personalized interventions that address the unique needs of MDD patients, tailored to their gender and age, and necessitate the development of antidepressant medications targeted at each gender-age subgroup.