Brain-aging related protein expression and imaging characteristics of mice exposed to chronic hypoxia at high altitude.

Objective: To determine changes in protein expression related to brain aging and imaging features in mice after chronic hypoxia exposure at high altitude. Method: A total of 24 healthy 4-week-old mice were randomly divided into high altitude hypoxia (HH) and plain control (PC) groups (n = 8 per group). HH mice were transported from Xi'an (450 m above sea level) to Maduo (4,300 m above sea level) while PC mice were raised in Xi'an. After 6 months, 7.0T magnetic resonance imaging (MRI) was performed. All mice completed T2-weighted imaging (T2WI), diffusion tensor imaging (DTI), resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL), and magnetic resonance angiography (MRA) examinations. Next, brain slices were prepared and Nissl staining was used to observe morphological changes in neurons. Ultrastructural changes in neurons were observed by transmission electron microscopy. Expression changes of Caspase-3, klotho, P16, P21, and P53 at the gene and protein levels were detected by real-time PCR (RT-PCR) and Western blot. Results: The number of neuronal Nissl bodies in the hippocampus and frontal cortex was significantly decreased in the HH group compared to the PC group. Some hippocampal and frontal cortical neurons were apoptotic, the nuclei were wrinkled, chromatin was aggregated, and most mitochondria were mildly swollen (crista lysis, fracture). Compared with the PC group, the HH group showed elevated expression of caspase-3 mRNA, P16 mRNA, P21 mRNA, and P53 mRNA in the hippocampus and frontal cortex. Expression of Klotho mRNA in the frontal cortex was also significantly decreased. Western blot results showed that caspase-3 protein expression in the hippocampus and frontal cortex of the HH group was increased compared with the PC group. Moreover, there was decreased Klotho protein expression and significantly increased P-P53 protein expression. Compared with the PC group, expression of P16 protein in the frontal cortex of the HH group was increased and the gray matter (GM) volume in the left visceral area, left caudate nucleus, and left piriform cortex was decreased. Furthermore, the amplitude of low frequency fluctuation was decreased in the left posterior nongranular insular lobe, right small cell reticular nucleus, left flocculus, left accessory flocculus, and left primary auditory area, but increased in the GM layer of the left superior colliculus. Regional homogeneity was decreased in the left and right olfactory regions, but increased in the left bed nucleus. After exposure to high altitude, functional connectivity (FC) between the bilateral caudate nucleus and thalamus, corpus callosum, cingulate gyrus, anterior limbic cortex, globus pallidus, and hippocampus was weakened. FC between the right caudate nucleus and hypothalamus and entorhinal cortex was also weakened. The fractional anisotropy value of the left hippocampus was decreased in the HH group. Compared with the PC group, the HH group showed significantly increased inner diameters of the bilateral common carotid artery and left internal carotid artery. The cerebral blood flow values of the bilateral cortex and bilateral hippocampus in the HH group did not change significantly. Conclusion: Taken together, our findings show that chronic hypoxia exposure at high altitude may promote neuronal apoptosis and abnormal expression of related proteins, changing the structure and function of brain. These changes may contribute to brain aging.

Differentiation of retroperitoneal paragangliomas and schwannomas based on computed tomography radiomics.

The purpose of this study was to differentiate the retroperitoneal paragangliomas and schwannomas using computed tomography (CT) radiomics. This study included 112 patients from two centers who pathologically confirmed retroperitoneal pheochromocytomas and schwannomas and underwent preoperative CT examinations. Radiomics features of the entire primary tumor were extracted from non-contrast enhancement (NC), arterial phase (AP) and venous phase (VP) CT images. The least absolute shrinkage and selection operator method was used to screen out key radiomics signatures. Radiomics, clinical and clinical-radiomics combined models were built to differentiate the retroperitoneal paragangliomas and schwannomas. Model performance and clinical usefulness were evaluated by receiver operating characteristic curve, calibration curve and decision curve. In addition, we compared the diagnostic accuracy of radiomics, clinical and clinical-radiomics combined models with radiologists for pheochromocytomas and schwannomas in the same set of data. Three NC, 4 AP, and 3 VP radiomics features were retained as the final radiomics signatures for differentiating the paragangliomas and schwannomas. The CT characteristics CT attenuation value of NC and the enhancement magnitude at AP and VP were found to be significantly different statistically (P < 0.05). The NC, AP, VP, Radiomics and clinical models had encouraging discriminative performance. The clinical-radiomics combined model that combined radiomics signatures and clinical characteristics showed excellent performance, with an area under curve (AUC) values were 0.984 (95% CI 0.952-1.000) in the training cohort, 0.955 (95% CI 0.864-1.000) in the internal validation cohort and 0.871 (95% CI 0.710-1.000) in the external validation cohort. The accuracy, sensitivity and specificity were 0.984, 0.970 and 1.000 in the training cohort, 0.960, 1.000 and 0.917 in the internal validation cohort and 0.917, 0.923 and 0.818 in the external validation cohort, respectively. Additionally, AP, VP, Radiomics, clinical and clinical-radiomics combined models had a higher diagnostic accuracy for pheochromocytomas and schwannomas than the two radiologists. Our study demonstrated the CT-based radiomics models has promising performance in differentiating the paragangliomas and schwannomas.

GSI CTA evaluation of the vertebrobasilar artery in normal adults at high altitude.

Objective: Vascular geometry is influenced by several factors during its growth and development. Here, we compared the differences in vertebrobasilar geometry among residents of a plateau region at different altitudes and investigated the relationship between vascular geometry and altitude. Methods: Data of some adults in the plateau region who experienced vertigo and headache as the main symptoms but had no evident abnormalities found during imaging examination were collected. They were divided into three groups based on an altitude gradient: group A (1,800-2,500 masl), group B (2,500-3,500 masl), and group C (over 3,500 masl). They underwent head-neck energy-spectrum computed tomography angiography with a gemstone spectral imaging scanning protocol. The following indices were observed: (1) vertebrobasilar geometric configurations (walking, tuning fork, lambda, and no confluence), (2) vertebral artery (VA) hypoplasia, (3) the bending number of bilateral VA intracranial segment, (4) length and tortuosity of the basilar artery (BA), and (5) anteroposterior (AP)-mid-BA angle, BA-VA angle, lateral-mid-BA angle, and VA-VA angle. Results: Of the 222 subjects, 84 of them were included in group A, 76 in group B, and 62 in group C. The number of participants in walking, tuning fork, lambda, and no confluence geometries was 93, 71, 50, and 8, respectively. As altitude increased, the tortuosity of the BA also increased (1.05 ± 0.06 vs. 1.06 ± 0.08 vs. 1.10 ± 0.13, P = 0.005), as did the lateral-mid-BA angle (23.18° ± 9.53° vs. 26.05° ± 10.10° vs. 31.07° ± 15.12°, P = 0.007) and the BA-VA angle (32.98° ± 17.85° vs. 34.51° ± 17.96° vs. 41.51° ± 19.22°, P = 0.024). There was a relatively weak positive correlation between the altitude and the tortuosity of the BA (rs = 0.190, P = 0.005), the lateral-mid-BA angle (rs = 0.201, P = 0.003), and the BA-VA angle (rs = 0.183, P = 0.006) which showed a significant difference. Compared with groups A and B, there were more multibending groups and fewer oligo-bending groups in group C (P < 0.001). There was no difference found in the vertebral artery hypoplasia, actual length of the BA, VA-VA angle, and AP-mid-BA angle among the three groups. Conclusion: As the altitude increased, the tortuosity of the BA and the sagittal angle of the vertebrobasilar arterial system also increased. The increase in altitude can lead to changes in vertebrobasilar geometry.

7T Small Animal MRI Research for Hepatic Alveolar Echinococcosis.

OBJECTIVES: 7T small animal magnetic resonance imaging (MRI) was used to analyze the growth characteristics of hepatic alveolar echinococcosis (HAE). METHODS: A mouse model of HAE was established by intraperitoneal injection of alveolar Echinococcus tissue suspension. Ten mouse models successfully inoculated by ultrasound screening were selected. The mouse model was scanned with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) sequence by 7T small animal MRI. Size, morphology, boundary, signal, and relationship with surrounding tissues of the lesions were recorded as characteristic alterations. Mice were killed at the end of the experiment, and the pathological specimens were taken for routine hematoxylin and eosin staining. RESULTS: Lesions were mainly located in the right lobe of the liver. The multivesicular structure is the characteristic manifestation of this disease. In the liver, lesions invaded the portal vein and were mainly distributed at the hepatic hilum. The left branch of the portal vein was mainly invaded. The mean diameter of the lesions in the left lobe of the liver was larger than in other parts of the liver. The mean diameter of the cystic solid lesions was greater than the multilocular cystic lesions. HAE showed hypointense on T1WI, hyperintense on T2WI, and hypointense on DWI; the marginal zone of the lesion showed hyperintensity on DWI and grew toward the hilum. The MRI features of intraperitoneal lesions were similar to those of intrahepatic lesions. Intraperitoneal lesions increased faster than intrahepatic lesions in the same period. CONCLUSION: Polyvesicular structure is a characteristic manifestation of hepatic alveolar echinococcosis in mice. The noninvasive monitoring of liver HAE in mice by 7T small animal MRI provides a visual basis for the diagnosis and treatment integration of HAE.

Therapeutic effect on Alveolar echinococcosis by targeting EM-Leucine aminopeptidase.

Alveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis Leucine aminopeptidase (EM-LAP) induced specific immune response and had an inhibiting effect on the parasites. In this study, the therapeutic effect of recombinant EM-LAP (rEM-LAP) on AE was evaluated and verified using Ubenimex, a broad-spectrum inhibitor of LAP. The results reveal that rEM-LAP could inhibit cyst growth and invasion and induce specific immunity response in BALB/c mice infected with E. multilocularis protoscoleces. The ultrasonic, MRI, and morphological results show that treatment with rEM-LAP inhibits E. multilocularis infection and reduces cyst weight, number, fibrosis and invasion. The same effect is observed for the treatment with Ubenimex by inhibiting LAP activity. The indirect ELISA shows that rEM-LAP could induce specific immunity response and produce high levels of IgG, IgG1, IgG2a, IgM, and IgA, and the serum levels of IFN-γ and IL-4 are significantly increased compared to the control groups, indicating that treatment with rEM-LAP leads to a Th1 and Th2 mixed-type immune response. This study suggests that EM-LAP could be a potential therapeutic target of E. multilocularis infection.

Magnetic resonance imaging study of normal cranial bone marrow conversion at high altitude.

Background: To use conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) to investigate the effects of long-term hypoxia on cranial bone marrow conversion in healthy people at high altitudes. Methods: A total of 1,130 individuals were selected from altitudinal areas of 2,000-3,000, 3,100-4,000, and >4,100 m. Each altitude range was divided into 5 age groups: 0-5, 6-14, 15-29, 30-49, and ≥50 years. Firstly, cranial bone marrow typing of the participants in each altitude range was performed on sagittal T1-weighted images (T1WI) according to the average diploe thickness and signal intensity of the normal skull, and the relationship between bone marrow conversion and age was analyzed. Secondly, the apparent diffusion coefficient (ADC) values of the frontal bone, parietal bone, occipital bone, and temporal bone were measured in the DWI post-processing workstation and statistical methods were used to analyze whether different altitudinal gradients and long-term hypoxic environment had any effect on cranial bone marrow conversion. Results: There was a positive correlation between bone marrow type and age in the healthy populations at all 3 levels of altitude (P<0.05). The average thickness of the cranial diploe also positively correlated with age (P<0.05); in the age ranges of 30-49 and ≥50 years, the ADC values of the occipital and temporal bone marrow positively correlated with increasing altitude (P<0.05). Conclusions: The cranial bone marrow of normal people at high altitudes changes from Type I to Type IV with increasing age and under the influence of long-term chronic hypoxia. The bone marrow of the occipital and temporal bones of healthy people aged 30-49 and ≥50 years showed erythromedularization during the process of Type III and IV bone marrow conversion.

One-tube nested MGB Probe Real-time PCR assay for detection of Echinococcus multilocularis infection in plasma cell free DNA.

INTRODUCTION: The main objective of this study was to develop a One-tube nested MGB probe real-time PCR Assay for detecting Echinococcus multilocularis infection in human plasma cell free DNA (cfDNA). METHODS: cfDNA was extracted from 10 E.m.-infected patients using a NucleoSnap DNA Plasma Kit and characterized by genomic sequencing. We designed nested PCR primers and MGB probe for Echinococcus multilocularis detection. The specificity, sensitivity and reproducibility of this assay were analyzed, and its validity was confirmed in 13 early stage clinical samples. RESULTS: Several Echinococcus multilocularis-specific sequences were detected in the cfDNA of E.m.-infected patients, and CBLO020001206.1 was selected as the candidate sequence. We designed the primers and probe for the one tube nested real-time PCR. No cross-reactions with E.g. were observed. The detection limit was as low as 1 copy for Echinococcus multilocularis. The coefficients of variation were lower than 5% in intra- and inter-assays. 11 out of 13 patients were positive with nested MGB Probe PCR Assay and 3 patients were positive without outer primer in early stage Alveolar Echinococcosis pateints. CONCLUSION: The one-tube nested MGB probe real-time PCR assay is a simple, rapid, and cost-effective method for detection of Echinococcus multilocularis infection in patients' Plasma DNA.

Study of high-altitude cerebral edema using multimodal imaging.

Objective: To analyze the brain imaging features of high-altitude cerebral edema (HACE) using computed tomography (CT) and multi-sequence magnetic resonance imaging (MRI) and to explore its injury characteristics. Materials and methods: We selected 30 patients with HACE diagnosed between January 2012 to August 2022 as the experimental group and 60 patients with dizziness on traveling from the plain to the plateau or from lower altitude to higher altitude in a short period of time as the control group. We collected general clinical data from the experimental group and classified it according to clinical symptoms. In both groups, we then performed a head CT and multi-sequence MRI (T1WI, T2WI, FLAIR, and DWI). Among them, nine patients with HACE were also scanned using susceptibility-weighted imaging (SWI). Finally, we analyzed the images. Results: According to clinical symptoms, we divided the 30 cases of HACE into 12 mild cases and 18 severe cases. There was no significant difference in sex, age, leukocyte, neutrophil, or glucose content between mild and severe HACE. The sensitivity and specificity of the MRI diagnosis were 100 and 100%, respectively, while the sensitivity and specificity of the CT diagnosis were 23.3 and 100%, respectively. The distribution range of deep and juxtacortical white matter edema was significantly larger in severe HACE than in mild HACE (p < 0.001). The corpus callosum edema distribution range in severe HACE was significantly larger than that in mild HACE (p = 0.001). The ADC value of the splenium of the corpus callosum was significantly lower in severe HACE than in mild HACE (p = 0.049). In mild and severe HACE, the signal intensity of the DWI sequence was significantly higher than that of conventional MRI sequences (T1WI, T2WI, FLAIR) (p = 0.008, p = 0.025, respectively). In severe HACE, seven cases showed bilateral corticospinal tract edema at the thalamic level, and SWI showed cerebral microbleeds (CMBs) in five cases, especially in the corpus callosum. Conclusions: MRI has more advantages than CT in the evaluation of HACE, especially in the DWI sequence. The white matter injury of severe HACE is more severe and extensive, especially in the corpus callosum, and some CMBs and corticospinal tract edema may also appear.

Development of a Nomogram Combining Clinical Risk Factors and Dual-Energy Spectral CT Parameters for the Preoperative Prediction of Lymph Node Metastasis in Patients With Colorectal Cancer.

OBJECTIVE: This study aimed to develop a dual-energy spectral computed tomography (DESCT) nomogram that incorporated both clinical factors and DESCT parameters for individual preoperative prediction of lymph node metastasis (LNM) in patients with colorectal cancer (CRC). MATERIAL AND METHODS: We retrospectively reviewed 167 pathologically confirmed patients with CRC who underwent enhanced DESCT preoperatively, and these patients were categorized into training (n = 117) and validation cohorts (n = 50). The monochromatic CT value, iodine concentration value (IC), and effective atomic number (Eff-Z) of the primary tumors were measured independently in the arterial phase (AP) and venous phase (VP) by two radiologists. DESCT parameters together with clinical factors were input into the prediction model for predicting LNM in patients with CRC. Logistic regression analyses were performed to screen for significant predictors of LNM, and these predictors were presented as an easy-to-use nomogram. The receiver operating characteristic curve and decision curve analysis (DCA) were used to evaluate the clinical usefulness of the nomogram. RESULTS: The logistic regression analysis showed that carcinoembryonic antigen, carbohydrate antigen 199, pericolorectal fat invasion, ICAP, ICVP, and Eff-ZVP were independent predictors in the predictive model. Based on these predictors, a quantitative nomogram was developed to predict individual LNM probability. The area under the curve (AUC) values of the nomogram were 0.876 in the training cohort and 0.852 in the validation cohort, respectively. DCA showed that our nomogram has outstanding clinical utility. CONCLUSIONS: This study presents a clinical nomogram that incorporates clinical factors and DESCT parameters and can potentially be used as a clinical tool for individual preoperative prediction of LNM in patients with CRC.

Kodama-XUUB: an informative classification for alveolar echinococcosis hepatic lesions on magnetic resonance imaging.

OBJECTIVE: To propose a modification of the Kodama classification to classify type III lesions of alveolar echinococcosis (AE) that do not have microcysts. MATERIALS AND METHODS: 200 magnetic resonance imaging (MRI) images of AE liver lesions from four endemic regions of the world were classified according to Kodama, distinguishing within type III those with microcysts from those without. Each center included 50 MRIs of patients with unoperated AA liver lesions. The first 50 cases were classified by a first reader in the presence of four second-line readers from each region. Then each second-line reader classified his or her 50 cases. RESULTS: In all centers, type III lesions were predominant: 58% of the total lesions and 23% of them were without microcysts. The average age of the patients was 47 years. In China, the patients were on average younger and the lesions larger. German patients had more lesions within the liver. Type I and II lesions, synonymous with earlier diagnosis, were more common in Europe. CONCLUSION: The Kodama classification needed to be modified because of the existence of a significant proportion of unclassifiable lesions. This is especially true since the presence of microcysts is an informative element of parasite activity. Therefore, this study proposes a Kodama-XUUB classification with type IIIa lesions having microcysts and type IIIb lesions not having microcysts.

TITLE: Kodama-XUUB : une classification informative des lésions hépatiques de l'échinococcose alvéolaire à l'Imagerie par Résonance Magnétique. ABSTRACT: Objectif : Proposer une modification de la classification de Kodama permettant de classer les lésions de type III qui ne présentent pas de microkystes. Matériels et Méthodes : 200 IRM de lésions hépatiques d'EA en provenance de quatre régions d'endémie dans le monde ont été classées selon Kodama, en distinguant au sein du type III celles qui présentaient des microkystes de celle qui n'en présentaient pas. Chaque centre a inclus 50 IRM de patients avec lésions hépatiques d'EA non opérées. Les 50 premiers cas ont été classés par un premier lecteur en présence des quatre seconds lecteurs issus de chacune des régions. Puis chaque second lecteur a classé ses 50 cas. Résultats : Dans tous les centres, les lésions de type III étaient largement prédominantes : 58 % du total des lésions et 23 % d'entre elles ne présentaient pas de microkystes. La moyenne d'âge des patients était de 47 ans. En Chine, les patients étaient en moyenne plus jeunes et les lésions plus larges. Les patients allemands présentaient plus de lésions au sein du foie. Les lésions de type I et II, synonymes de diagnostic plus précoce étaient plus fréquentes en Europe. Conclusion : La classification de Kodama nécessitait d'être modifiée du fait de l'existence d'une proportion non négligeable de lésions non classifiables. Ce d'autant que la présence de microkystes est un élément informatif de l'activité du parasite. C'est pourquoi cette étude propose une classification Kodama-XUUB avec un type IIIa de lésions avec microkystes et un type IIIb sans microkystes.

Predicting Microsatellite Instability Status in Colorectal Cancer Based on Triphasic Enhanced Computed Tomography Radiomics Signatures: A Multicenter Study.

BACKGROUND: This study aimed to develop and validate a computed tomography (CT)-based radiomics model to predict microsatellite instability (MSI) status in colorectal cancer patients and to identify the radiomics signature with the most robust and high performance from one of the three phases of triphasic enhanced CT. METHODS: In total, 502 colorectal cancer patients with preoperative contrast-enhanced CT images and available MSI status (441 in the training cohort and 61 in the external validation cohort) were enrolled from two centers in our retrospective study. Radiomics features of the entire primary tumor were extracted from arterial-, delayed-, and venous-phase CT images. The least absolute shrinkage and selection operator method was used to retain the features closely associated with MSI status. Radiomics, clinical, and combined Clinical Radiomics models were built to predict MSI status. Model performance was evaluated by receiver operating characteristic curve analysis. RESULTS: Thirty-two radiomics features showed significant correlation with MSI status. Delayed-phase models showed superior predictive performance compared to arterial- or venous-phase models. Additionally, age, location, and carcinoembryonic antigen were considered useful predictors of MSI status. The Clinical Radiomics nomogram that incorporated both clinical risk factors and radiomics parameters showed excellent performance, with an AUC, accuracy, and sensitivity of 0.898, 0.837, and 0.821 in the training cohort and 0.964, 0.918, and 1.000 in the validation cohort, respectively. CONCLUSIONS: The proposed CT-based radiomics signature has excellent performance in predicting MSI status and could potentially guide individualized therapy.

Development of a dual-energy spectral computed tomography-based nomogram for the preoperative discrimination of histological grade in colorectal adenocarcinoma patients.

BACKGROUND: The usefulness of a dual-energy spectral computed tomography (DESCT)-based nomogram in discriminating between histological grades of colorectal adenocarcinoma (CRAC) is unclear. This study aimed to develop such a nomogram and assess its ability to preoperatively discriminate between histological grades in CRAC patients. METHODS: Primary tumors monochromatic CT value, iodine concentration (IC) value, and effective atomic number (Eff-Z) in the arterial (AP) and venous phases (VP) were retrospectively compared between patients with high-grade (n=65) and low-grade (n=108) CRAC who underwent preoperative abdominal DESCT. Univariate analysis was used to compare the DESCT parameters and clinical factors between these two patient groups. Statistically significant features in the univariate analysis were included in the multivariate logistic regression model to identify the indicators for building a nomogram that could discriminate between histological grades in CRAC patients. The clinical usefulness of the nomogram and its value for predicting overall survival were statistically evaluated. RESULTS: The logistic regression analysis showed that age, clinical T stage, clinical N stage, and IC values in AP and VP were significant independent predictors for high-grade CRAC. A quantitative nomogram developed based on these predictors showed excellent performance for discriminating between the histological grades, with an area under the curve (AUC) of 0.886 and excellent agreement in the calibration curve. The Kaplan-Meier curve for overall survival showed that our nomogram identified a significant difference between the high- and low-risk groups [hazard ratio (HR), 2.188; 95% CI, 1.072-4.465; P=0.027). CONCLUSIONS: This study presents a nomogram that incorporates DESCT parameters and clinical factors and can potentially be used as a clinical tool for individual preoperative prediction of CRAC histological grade.

Development of a dual-energy spectral CT based nomogram for the preoperative discrimination of mutated and wild-type KRAS in patients with colorectal cancer.

PURPOSE: To develop a dual-energy spectral CT (DESCT) nomogram for the preoperative identification of KRAS mutation in patients with colorectal cancer (CRC). METHOD: One hundred and twenty-four patients who underwent energy spectrum CT pre-operatively were recruited and split into mutated KRAS group (n = 50) and wild-type KRAS group (n = 74). DESCT parameters, including monochromatic CT value, iodine concentration, water concentration, and effective atomic number were measured independently by two reviewers in the arterial, venous, and delayed phases. Normalized iodine concentration (NIC) and slope k of the spectral HU curve were calculated. Evaluate other imaging features such as ATL/LTL ratio, tumor gross pattern, pericolorectal fat invasion (PFI) was also performed by these reviewers. Independent predictors for KRAS mutation were screened out using logistic regression, and these predictors were presented as a nomogram. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the clinical usefulness of the nomogram. RESULTS: The slope k in the arterial phase, effective atomic number in the arterial phase, NIC in the venous phase, ATL/LTL ratio and PFI were significant independent predictors for KRAS mutation. Based on these independent predictors, a quantitative nomogram was developed to predict individual KRAS mutation probability. The nomogram had excellent performance with an AUC of 0.848 and excellent calibration. DCA showed that our nomogram has outstanding clinical utility. CONCLUSIONS: This study demonstrates that a DESCT based nomogram has potential value for individual preoperative identification of KRAS mutation in CRC patients.

Intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis: a multicenter cohort study.

BACKGROUND: The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE. PURPOSE: To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China. MATERIAL AND METHODS: Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama's classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion. RESULTS: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher's exact test: P=0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06; P = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ2 = 11.92; P = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; P<0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations. CONCLUSION: Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.

Study of Brain Structure and Function in Chronic Mountain Sickness Based on fMRI.

Objective: Headache and memory impairment are the primary clinical symptoms of chronic mountain sickness (CMS). In this study, we used voxel-based morphometry (VBM) and the amplitude of the low-frequency fluctuation method (ALFF) based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to identify changes in the brain structure and function caused by CMS. Materials and Methods: T1W anatomical images and a resting-state functional MRI (fMRI) of the whole brain were performed in 24 patients diagnosed with CMS and 25 normal controls matched for age, sex, years of education, and living altitude. MRI images were acquired, followed by VBM and ALFF data analyses. Results: Compared with the control group, the CMS group had increased gray matter volume in the left cerebellum crus II area, left inferior temporal gyrus, right middle temporal gyrus, right insula, right caudate nucleus, and bilateral lentiform nucleus along with decreased gray matter volume in the left middle occipital gyrus and left middle temporal gyrus. White matter was decreased in the bilateral middle temporal gyrus and increased in the right Heschl's gyrus. Resting-state fMRI in patients with CMS showed increased spontaneous brain activity in the left supramarginal gyrus, left parahippocampal gyrus, and left middle temporal gyrus along with decreased spontaneous brain activity in the right cerebellum crus I area and right supplementary motor area. Conclusion: Patients with CMS had differences in gray and white matter volume and abnormal spontaneous brain activity in multiple brain regions compared to the controls. This suggests that long-term chronic hypoxia may induce changes in brain structure and function, resulting in CMS.

Parasite Circulating Cell-free DNA in the Blood of Alveolar Echinococcosis Patients as a Diagnostic and Treatment-Status Indicator.

BACKGROUND: Alveolar echinococcosis (AE) is a serious parasitic disease caused by the larvae of Echinococcus multilocularis. It is the less common but substantially more deadly of the 2 major echinococcosis diseases that can occur globally but are concentrated in central Asia. METHODS: We analyzed parasite circulating cell-free DNA (cfDNA) in 149 plasma samples using a DNA sequencing-based method (105 AE, 16 cystic echinococcosis, 4 liver cancer, 4 gallstones, and 20 healthy volunteers). After identifying the Echinococcus-specific cfDNA (Em-cfDNA) sequences in the samples, we determined whether Em-cfDNA could be used for AE diagnosis and as a potential indicator of the effectiveness of surgical treatment. We also examined potential associations between Em-cfDNA levels and clinical features of AE patients. RESULTS: Our work demonstrates that varying reads of Em-cfDNA were detectable in the plasma of 100% of preoperative AE patients and that all of the non-AE patients and healthy volunteers were negative. Em-cfDNA has good sensitivity and specificity for the diagnosis of AE. We also found that Em-cfDNA levels apparently have reference value for evaluating the therapeutic efficacy of surgery interventions for AE lesions. Finally, our analysis revealed that Em-cfDNA levels can reflect meaningful information about lesion size in preoperative AE patients. CONCLUSIONS: We demonstrate that sequencing-based monitoring of Em-cfDNA can be used in the clinic as a powerful diagnostic indicator for AE. We also note that there is a strong potential for use of this liquid-biopsy method to monitor ongoing disease status in postintervention AE patients.

Resting-state functional magnetic resonance imaging of high altitude patients with obstructive sleep apnoea hypopnoea syndrome.

The objective of the study was to observe brain function changes in Obstructive Sleep Apnoea Hypopnoea Syndrome (OSAHS) patients at high altitude. Resting-state functional magnetic resonance imaging (rs-fMRI) in patients with OSAHS was assessed using regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC). In this study, 36 male patients with OSAHS and 38 healthy male subjects were recruited from high-altitude areas, specifically, altitudes of 2,000-3,000 m. OSAHS was diagnosed by polysomnography (PSG). The blood oxygen level-dependent (BOLD) signals of OSAHS patients and healthy controls in the resting state were obtained and compared using ReHo, ALFF and FC methods. The posterior cingulate cortex (PCC) was selected as the seed region in the comparison of FC between the two groups. Compared with the healthy control group, multiple brain functions in the OSAHS patient group were different. There were correlations between the brain function values of some brain regions and demographic data. We also found that in contrast to earlier findings with individuals in plains areas, the brain function at the frontal lobe and the precuneus were higher in OSAHS patients, and the PCC showed higher FC with the left caudate, which may be due to the high-altitude hypoxic environment.

Evaluation of intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis.

BACKGROUND: The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE. AIM: To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim. METHODS: Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations (n = 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States). RESULTS: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (P = 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size (P = 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe (P < 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III (P < 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III. CONCLUSION: Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.