High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes.

OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: • The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. • The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. • Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.

Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway.

Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.

Multimode heralded single photons based on the DLCZ.

High-quality single-photon sources are crucial for the development of simple quantum devices. Quantum communication stands at the forefront of cutting-edge technologies, promising unprecedented levels of security and efficiency. A cornerstone of this revolutionary field is the development of high-speed single-photon sources, which play a pivotal role in quantum key distribution and other quantum communication protocols. In this context, the concept of space multimode emerges as a promising avenue to propel the capabilities of single-photon sources to new heights. We have spatial multiplexing technology to develop single-photon sources that deliver high-speed heralded single photons in the Duan-Lukin-Cirac-Zoller (DLCZ) scheme. We propose a spatial multiplexing single-photon source scheme based on the DLCZ. Compared to a single spatial mode, by adding six spatial modes through spatial multiplexing, the single-photon generation rate increases 4.3 times. And the second-order correlation function of single photons is less than 0.5. We show that expanding the spatial degrees of freedom of the quantum storage scheme based on DLCZ does not affect the single-photon properties. The generation rate of the single photon can be significantly increased through spatial multiplexing with a feedback circuit. Our approach offers a promising path to creating a high-speed photon source based on a spatial multimode scheme.

Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis.

AIMS: Blood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis. METHODS AND RESULTS: Immunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4-/-, and Il13-/- mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-ß receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries. CONCLUSION: Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.

Regulating the Coordination Geometry and Oxidation State of Single-Atom Fe Sites for Enhanced Oxygen Reduction Electrocatalysis.

FeNC catalysts demonstrate remarkable activity and stability for the oxygen reduction reaction (ORR) in polymer electrolyte membrane fuel cells and Zn-air batteries (ZABs). The local coordination of Fe single atoms in FeNC catalysts strongly impacts ORR activity. Herein, FeNC catalysts containing Fe single atoms sites with FeN3 , FeN4 , and FeN5 coordinations are synthesized by carbonization of Fe-rich polypyrrole precursors. The FeN5 sites possess a higher Fe oxidation state (+2.62) than the FeN3 (+2.23) and FeN4 (+2.47) sites, and higher ORR activity. Density functional theory calculations verify that the FeN5 coordination optimizes the adsorption and desorption of ORR intermediates, dramatically lowering the energy barrier for OH- desorption in the rate-limiting ORR step. A primary ZAB constructed using the FeNC catalyst with FeN5 sites demonstrates state-of-the-art performance (an open circuit potential of 1.629 V, power density of 159 mW cm-2 ). Results confirm an intimate structure-activity relationship between Fe coordination, Fe oxidation state, and ORR activity in FeNC catalysts.

Cavity-enhanced and temporally multiplexed atom-photon entanglement interface.

Practical realization of quantum repeaters requires quantum memories with high retrieval efficiency, multi-mode storage capacities, and long lifetimes. Here, we report a high-retrieval-efficiency and temporally multiplexed atom-photon entanglement source. A train of 12 write pulses in time is applied to a cold atomic ensemble along different directions, which generates temporally multiplexed pairs of Stokes photons and spin waves via Duan-Lukin-Cirac-Zoller processes. The two arms of a polarization interferometer are used to encode photonic qubits of 12 Stokes temporal modes. The multiplexed spin-wave qubits, each of which is entangled with one Stokes qubit, are stored in a "clock" coherence. A ring cavity that resonates simultaneously with the two arms of the interferometer is used to enhance retrieval from the spin-wave qubits, with the intrinsic retrieval efficiency reaching 70.4%. The multiplexed source gives rise to a ∼12.1-fold increase in atom-photon entanglement-generation probability compared to the single-mode source. The measured Bell parameter for the multiplexed atom-photon entanglement is 2.21(2), along with a memory lifetime of up to ∼125 µs.

The Effect and Mechanism of Syringa pinnatifolia Hemsl. Ligans on Cerebral Ischemia-Reperfusion Injury and Oxidative Stress in Mice.

Lignans are the main components of Syringa pinnatifolia Hemsl. (SP). Previous studies have shown that SP lignans (SPL) can considerably improve CCl4-induced acute liver injury in mice by the anti-oxidative stress (OS) mechanism. In this study, we investigated the antioxidant effects of SPL on cerebral ischemia/reperfusion injury (CIRI) and its underlying molecular mechanism. We developed a middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice to achieve CIRI and orally administered SPL daily for 1-3 days. We evaluated neurological function deficits and performed hematoxylin and eosin staining. We further calculated the infarct volume. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the brain were detected using corresponding kits. The transcription and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in brain tissues were analyzed by real-time reverse transcription polymerase chain reaction and western blotting, respectively. The results showed that SPL could remarkably ameliorate neurological functions and pathological damage in brain tissues, reducing the cerebral infarct volume. It also increased the SOD and GPx activities decreased the MDA levels as well as inhibited the expression of (NOX)2 and NOX4. We also found that the mRNA and protein levels of Nrf2, HO-1, and NQO1 in the CIRI mice increased transiently and peaked at 24 h of reperfusion, and then began to decline. SPL could reverse decreasing Nrf2 and HO-1 levels after 24 h. In conclusion, SPL can alleviate CIRI and OS by activating the Nrf2/HO-1 pathway.

Supervised convex clustering.

Clustering has long been a popular unsupervised learning approach to identify groups of similar objects and discover patterns from unlabeled data in many applications. Yet, coming up with meaningful interpretations of the estimated clusters has often been challenging precisely due to their unsupervised nature. Meanwhile, in many real-world scenarios, there are some noisy supervising auxiliary variables, for instance, subjective diagnostic opinions, that are related to the observed heterogeneity of the unlabeled data. By leveraging information from both supervising auxiliary variables and unlabeled data, we seek to uncover more scientifically interpretable group structures that may be hidden by completely unsupervised analyses. In this work, we propose and develop a new statistical pattern discovery method named supervised convex clustering (SCC) that borrows strength from both information sources and guides towards finding more interpretable patterns via a joint convex fusion penalty. We develop several extensions of SCC to integrate different types of supervising auxiliary variables, to adjust for additional covariates, and to find biclusters. We demonstrate the practical advantages of SCC through simulations and a case study on Alzheimer's disease genomics. Specifically, we discover new candidate genes as well as new subtypes of Alzheimer's disease that can potentially lead to better understanding of the underlying genetic mechanisms responsible for the observed heterogeneity of cognitive decline in older adults.

Hyperoside mediates protection from diabetes kidney disease by regulating ROS-ERK signaling pathway and pyroptosis.

Renal tubular injury is a key factor in the progression of diabetic kidney disease to end-stage renal disease. Hyperoside, a natural flavonol glycoside in various plants, is a potentially effective drug for the clinical treatment of diabetic kidney disease. However, the specific mechanisms remain unknown. Therefore, this study will explore the effect and mechanism of hyperoside on renal tubulointerstitium in diabetic kidney disease. db/db mouse (C57BL/KsJ) is a model of type 2 diabetes resulting from Leptin receptor point mutations, with the appearance of diabetic kidney disease. Therefore, db/db mice were used for in vivo experimental studies. In vitro, human renal tubular epithelial cells were incubated with bovine serum albumin to simulate the injury of renal tubular epithelial cells caused by excessive albumin in primary urine. The experimental results showed that hyperoside could improve kidney function and reduce kidney tissue damage in mice, and could inhibit oxidative stress, extracellularly regulated protein kinases 1/2 signaling activation, and pyroptosis in human renal tubular epithelial cells. Therefore, hyperoside inhibited oxidative stress by regulating the activation of the extracellularly regulated protein kinases 1/2/mitogen-activated protein kinase signaling pathway, thereby alleviating proteinuria-induced pyroptosis in renal tubular epithelial cells. This study provides novel evidence that could facilitate the clinical application of hyperoside in diabetic kidney disease treatment.

A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study.

BACKGROUND: Currently, there is no clinically relevant non-invasive biomarker for early detection of esophageal squamous cell carcinoma (ESCC). Herein, we established and evaluated a circulating microRNA (miRNA)-based signature for the early detection of ESCC using a systematic genome-wide miRNA expression profiling analysis. METHODS: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n = 108, 238, and 216) and the candidate miRNAs were confirmed in tissue specimens (n = 64) by qRT-PCR. Using a serum training cohort (n = 408), we conducted multivariate logistic regression analysis to develop an ESCC circulating miRNA signature and the signature was subsequently validated in two independent retrospective and two prospective cohorts. RESULTS: We identified eighteen initial miRNA candidates from three miRNA expression datasets (n = 108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confirmed the overexpression of 8 miRNAs (miR-103, miR-106b, miR-151, miR-17, miR-181a, miR-21, miR-25, and miR-93) in serum specimens. Using a serum training cohort, we developed a circulating miRNA signature (AUC:0.83 [95%CI:0.79-0.87]) and the diagnostic performance of the miRNA signature was confirmed in two independent validation cohorts (n = 126, AUC:0.80 [95%CI:0.69-0.91]; and n = 165, AUC:0.89 [95%CI:0.83-0.94]). Finally, we demonstrated the diagnostic performance of the 8-miRNA signature in two prospective cohorts (n = 185, AUC:0.92, [95%CI:0.87-0.96]); and (n = 188, AUC:0.93, [95%CI:0.88-0.97]). Importantly, the 8-miRNA signature was superior to current clinical serological markers in discriminating early stage ESCC patients from healthy controls (p < 0.001). CONCLUSIONS: We have developed a novel and robust circulating miRNA-based signature for early detection of ESCC, which was successfully validated in multiple retrospective and prospective multinational, multicenter cohorts.

A liquid biopsy signature predicts lymph node metastases in T1 oesophageal squamous cell carcinoma: implications for precision treatment strategy.

BACKGROUND: The treatment strategies for T1 oesophageal squamous cell carcinoma (ESCC) patients with or without lymph node metastasis (LNM) are different. Given the advantages of the minimally invasive, sensitive and real-time detection, liquid biopsy has become an important cancer diagnostic and prognostic tool. METHODS: MiRNA array and small-RNA sequencing were performed. Then, 222 formalin-fixed and paraffin-embedded tumour samples and 229 pretreatment serum samples from T1 ESCC patients were used to verify and evaluate the results. RESULTS: We demonstrated that serum miR-20b-5p could predict LNM in T1 ESCC patients. The AUC for serum miR-20b-5p was higher (0.827) than those for lymphovascular invasion (LVI) (0.751, P = 0.2128), invasion depth (0.662, P = 0.0027) and tumour differentiation grade (0.634, P = 0.0019). A nomogram for predicting LNM with three independent significant predictors (miR-20b-5p, LVI and invasion depth) was constructed with a concordance index of 0.931. Serum miR-20b-5p was also significantly correlated with disease-free survival (P < 0.001). An algorithm of improved T1 ESCC treatment strategy after biopsy and/or after endoscopic resection based on serum miR-20b-5p level was constructed. CONCLUSIONS: This study suggests that serum miR-20b-5p is a potential biomarker for predicting LNM and can be helpful for precise clinical decision-making strategies and improve treatment outcomes for T1 ESCC patients.

Dynamic changes of serum metabolites associated with infection and severity of patients with acute hepatitis E infection.

Dynamic changes in metabolites may affect liver disease progression, and provide new methods for predicting liver damage. We used ultra-performance liquid chromatography-mass spectroscopy to assess serum metabolites in healthy controls (HC), and patients with acute hepatitis E (AHE) or hepatitis E virus acute liver failure (HEV-ALF). The principal component analysis, partial least squares discriminant analysis, and discriminant analysis of orthogonal projections to latent structures models illustrated significant differences in the metabolite components between AHE patients and HCs, or between HEV-ALF and AHE patients. In pathway enrichment analysis, we further identified two altered pathways, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, when comparing AHE patients with HCs. Linoleic acid metabolism and porphyrin and chlorophyll metabolism pathways were significantly different in HEV-ALF when compared with AHE patients. The discriminative performances of differential metabolites showed that taurocholic acid, glycocholic acid, glycochenodeoxycholate-3-sulfate, and docosahexaenoic acid could be used to distinguish HEV-ALF from AHE patients. The serum levels of glycocholic acid, taurocholic acid, deoxycholic acid glycine conjugate, and docosahexaenoic acid were associated with the prognosis of HEV-ALF patients. Dynamic changes in serum metabolites were associated with AHE infection and severity. The identified metabolites can be used to diagnose and predict the prognosis of HEV-ALF.

Generation of entanglement between a highly wave-packet-tunable photon and a spin-wave memory in cold atoms.

Controls of waveforms (pulse durations) of single photons are important tasks for effectively interconnecting disparate atomic memories in hybrid quantum networks. So far, the waveform control of a single photon that is entangled with an atomic memory remains unexplored. Here, we demonstrated control of waveform length of the photon that is entangled with an atomic spin-wave memory by varying light-atom interaction time in cold atoms. The Bell parameter S as a function of the duration of photon pulse is measured, which shows that violations of Bell inequality can be achieved for the photon pulse in the duration range from 40 ns to 50 µs, where, S = 2.64 ± 0.02 and S = 2.26 ± 0.05 for the 40-ns and 50-µs durations, respectively. The measured results show that S parameter decreases with the increase in the pulse duration. We confirm that the increase in photon noise probability per pulse with the pulse-duration is responsible for the S decrease.

Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy.

Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6-8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.

Potato protease inhibitor II prevents obesity by inducing browning of white adipose tissue in mice via ß3 adrenergic receptor signaling pathway.

There are currently few effective and safe pharmacologic means for inducing beige adipogenesis in humans. This study highlights the role of potato protease inhibitor II (PPI II) in regulating the browning of adipose tissue. The in vitro results showed that PPI II increased the expression of the uncoupling protein 1 (UCP1) protein and gene and beige-specific genes, including Cd137, Cited1, Tbx1, and Tmem26 in vitro. PPI II treatment for three months in diet-induced obesity mice increased the levels of the UCP1 protein in white adipose tissue, causing elevated energy expenditure, thus preventing obesity and improving glucose tolerance. Mechanistic studies further revealed that PPI II regulated the abundance and activity of ß3 adrenergic receptor (ß3 -AR) in white adipocytes. Chemical-inhibition experiments revealed the crucial role of ß3 -AR-dependent protein kinase A (PKA)-p38 kinase (p38)/extracellular signal-related kinase1/2 (ERK1/2) signaling in PPI II-mediated browning program of white adipose tissues. In summary, our findings highlight the role of PPI II in beige adipocyte differentiation and thermogenesis and provide new insights into its use in preventing obesity.

Potentially traumatic events and post-traumatic growth among Chinese peacekeepers: A moderated mediation model.

Peacekeepers are inherently exposed to potentially traumatic events (PTEs) in the line of duty. However, little is known about whether PTEs during peacekeeping missions may foster post-traumatic growth (PTG) among peacekeepers and its mechanisms. This study aimed to investigate the association between PTEs and PTG among Chinese peacekeepers, as well as the mediating role of coping style and the moderating role of resilience. Five hundred ninety-five Chinese peacekeepers completing the United Nations (UN) peacekeeping mission in South Sudan and returning to China were recruited to complete Peacekeeping Traumatic Stress Exposure Scale, Posttraumatic Growth Inventory, Simplified Coping Style Questionnaire and the Chinese version of Connor and Davidson's Resilience Scale. PTEs were positively associated with PTG among Chinese peacekeepers. Coping style partially mediated the association between PTEs and PTG. Resilience moderated the association between coping style and PTG. Specifically, at a lower level of resilience, positive coping style was more effective in predicting PTG. This study contributes to understanding the complex association between PTEs in peacekeeping missions, coping style, resilience and PTG by focusing on the experiences of Chinese peacekeepers and adds value to the current literature on psychological health in peacekeepers.

IgE Contributes to Atherosclerosis and Obesity by Affecting Macrophage Polarization, Macrophage Protein Network, and Foam Cell Formation.

OBJECTIVE: By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Yet, a direct role of IgE and its mechanisms in cardiometabolic diseases remain incompletely understood. Approach and Results: Using atherosclerosis prone Apoe-/- mice and IgE-deficient Ige-/- mice, we demonstrated that IgE deficiency reduced atherosclerosis lesion burden, lesion lipid deposition, smooth muscle cell and endothelial cell contents, chemokine MCP (monocyte chemoattractant protein)-1 expression and macrophage accumulation. IgE deficiency also reduced bodyweight gain and increased glucose and insulin sensitivities with significantly reduced plasma cholesterol, triglyceride, insulin, and inflammatory cytokines and chemokines, including IL (interleukin)-6, IFN (interferon)-γ, and MCP-1. From atherosclerotic lesions and peritoneal macrophages from Apoe-/-Ige-/- mice that consumed an atherogenic diet, we detected reduced expression of M1 macrophage markers (CD68, MCP-1, TNF [tumor necrosis factor]-α, IL-6, and iNOS [inducible nitric oxide synthase]) but increased expression of M2 macrophage markers (Arg [arginase]-1 and IL-10) and macrophage-sterol-responsive-network molecules (complement C3, lipoprotein lipase, LDLR [low-density lipoprotein receptor]-related protein 1, and TFR [transferrin]) that suppress macrophage foam cell formation. These IgE activities can be reproduced in bone marrow-derived macrophages from wild-type mice, but muted in cells from FcεR1-deficient mice, or blocked by anti-IgE antibody or complement C3 deficiency. CONCLUSIONS: IgE deficiency protects mice from diet-induced atherosclerosis, obesity, glucose tolerance, and insulin resistance by regulating macrophage polarization, macrophage-sterol-responsive-network gene expression, and foam cell formation.

MRI-based nomogram analysis: recognition of anterior peritoneal reflection and its relationship to rectal cancers.

BACKGROUND: This study is aimed to explore the factors influencing the visualization of the anterior peritoneal reflection (APR) and evaluated the feasibility of measuring the distance from the anal verge to APR (AV-APR), the tumor height on MRI and the accuracy of determining the tumor location with regard to APR. METHODS: We retrospectively analyzed 110 patients with rectal cancer. A univariate and multivariate logistic regression was performed to identify the independent factors (age, sex, T stage, the degree of bladder filling, pelvic effusion, intraoperative tumor location, BMI, uterine orientation, the distance from seminal vesicle/uterus to rectum) associated with the visualization of the APR on MRI. The nomogram diagram and receiver operating characteristic curve (ROC curve) were established. Intraclass correlation coefficient (ICC) was used to evaluate the consistency of the distance of AV-APR. The Pearson correlation coefficient was used to characterize the agreement between measurements of the tumor height by colonoscopy and MRI. The Kappa statistics was used to evaluate the value of MRI in the diagnosis of the tumor location with regard to the APR. RESULTS: Multivariate logistic regression showed that BMI (P = 0.031, odds ratio, OR = 1.197), pelvic effusion (P = 0.020, OR = 7.107) and the distance from seminal vesicle/uterus to the rectum (P = 0.001, OR = 3.622) were correlated with the visualization of APR. The cut-off point of BMI and the distance from seminal vesicle/uterus to the rectum is 25.845 kg/m2 and 1.15 cm. The area under curve (AUC) (95% Confidence Interval, 95% CI) of the combined model is 0.840 (0.750-0.930). The favorable calibration of the nomogram showed a non-significant Hosmer-Lemeshow test statistic (P = 0.195). The ICC value (95% CI) of the distance of AV-APR measured by two radiologists was 0.981 (0.969-0.989). The height measured by MRI and colonoscopy were correlated with each other (r = 0.699, P < 0.001). The Kappa value was 0.854. CONCLUSIONS: BMI, pelvic effusion, and the distance from seminal vesicle/uterus to rectum could affect the visualization of APR on MRI. Also, it's feasible to measure the distance of AV-APR, the tumor height, and to evaluate the tumor location with regard to APR using MRI.

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. METHODS: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. RESULTS: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). CONCLUSIONS: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.

A male-ABCD algorithm for hepatocellular carcinoma risk prediction in HBsAg carriers.

OBJECTIVE: Hepatocellular carcinoma (HCC) development among hepatitis B surface antigen (HBsAg) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBsAg-positive male adults. METHODS: HBsAg-positive males of 35-69 years old (N=6,153) were included from a multi-center population-based liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using B-ultrasonography and α-fetoprotein (AFP). We used logistic regression models to determine potential risk factors, built and examined the operating characteristics of a point-based algorithm for HCC risk prediction. RESULTS: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT (γ-glutamyl-transpeptidase), counts of platelets, white cells, concentration of DCP (des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91 (0.90-0.93), larger than existing models. At 1.5 points of risk score, 26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk, with positive prediction value of 22.85% and 12.35%, respectively. CONCLUSIONS: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.