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.

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.

Comparison of Carotid Atherosclerosis between Patients at High Altitude and Sea Level: A Chinese Atherosclerosis Risk Evaluation Study.

OBJECTIVES: To investigate the differences in characteristics of carotid plaques between patients Xining at high altitude and Jinan at sea level using magnetic resonance (MR) imaging. METHODS: Subjects were recruited from a cross-sectional, observational, multicenter imaging study of CARE-II study. Forty-nine (mean age 63.3 ± 12.0 years, 33 males) and 51 (mean age 64.5 ± 12.0 years, 34 males) patients were recruited from a site located in a high altitude region and a site located near sea level, respectively. All patients underwent multicontrast MR vessel wall imaging for carotid arteries on 3.0 T MR scanner. The carotid plaques features were compared between 2 patient groups. RESULTS: Compared with patients at sea level, those at high altitude had significantly greater lumen area (58.5 ± 17.8 mm2 versus 50.0 ± 19.6 mm2, P = .008), smaller maximum normalized wall index (48.6% ± 14.2% versus 57.8% ± 16.3%, P = .002), and smaller percentage volume of calcium (0.9% versus 5.6%, P < .001) in the symptomatic carotid artery. After adjustment for clinical risk factors including age, sex, systolic blood pressure, LDL-C, and statin use, these differences in plaque morphology and composition remained statistically significant. After further adjustment for normalized wall index as a measure of plaque burden, percentage volume of calcification was still significantly smaller in patients at high altitude area than that in patients at sea level area (P = .047). CONCLUSION: Symptomatic subjects from a high altitude area have lower plaque burden and less calcification in the carotid artery compared to those from an area near sea level.

Worldwide literature on epidemiology of human alveolar echinococcosis: a systematic review of research published in the twenty-first century.

PURPOSE: Human alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this systematic review is to establish a comprehensive global AE literature overview taking into account the epidemiologically relevant AE research of the twenty-first century. METHODS: We systematically searched the global literature published from 2001 through 2018 via MEDLINE, EMBASE, the Russian databases eLIBRARY.RU, CyberLeninka, the Chinese databases CNKI, VIP, Journals. RESEARCH: ac.ir (Farsi language-based), Jordan E-Library (Arab language-based) and supplementary Google Scholar, in accordance with the PRISMA guidelines. QGIS software was used for the mapping of the affected countries. RESULTS: We have listed 154 relevant publications in the final literature synopsis in consideration of our quality assessment. Including non-autochthonous cases, human AE was reported in 36 countries within the northern hemisphere from 2001 to 2018. The first publication of AE in Tajikistan, Pakistan, South Korea, Belgium, the Netherlands, Slovakia, Hungary, Lithuania, Latvia, Slovenia and Morocco occurred in this century; further first cases in Taiwan, Thailand, and Denmark were considered to be non-autochthonous by the authors. The highest total case numbers (n ≥ 100 in a single article) were reported in France, Germany, Switzerland, Poland, and Lithuania, including China and Kyrgyzstan with by far the highest prevalence figures. CONCLUSIONS: Our paper emphasises the increasing spread of reported cases and the rise in its numbers in the literature of the twenty-first century, especially in western, northern and eastern Europe, as well as in central Asia. Epidemiological studies on human infections are lacking in many parts of the world.

The value of nomogram analysis in prediction of cerebral spread of hepatic alveolar echinococcosis.

BACKGROUND: The prognosis after brain metastasis of alveolar echinococcosis is inferior, but there is currently no effective method to predict brain metastasis. PURPOSE: To explore the value of a nomogram constructed based on a CT plain scan and enhanced imaging features combined with clinical indicators in predicting brain metastasis of hepatic alveolar echinococcosis (HAE). MATERIALS AND METHODS: The imaging characteristics and clinical indicators of 116 patients diagnosed with HAE in the Affiliated Hospital of Qinghai University from 2015 to 2022 were retrospectively collected. The data were randomly divided into a training set and a validation set according to 7:3, and the difference between the two groups was analyzed. Binary logistic regression analysis was used to obtain independent predictors of brain metastasis in HAE, and a prediction model was constructed based on this and expressed in the form of a nomogram. Receiver operating characteristic (ROC) curve and calibration curve (CRC) were used to evaluate model performance, and decision curve analysis (DCA) was used to assess the clinical value of the predictive model. RESULT: A total of 116 HAE patients were included (average age 38.07±15.09 years old, 54 males and 62 females, 81 patients (70 %) in the training set, and 35 patients (30 %) in the validation set). There was no statistically significant difference between CT plain scan and enhanced imaging features combined with clinical indicators between the training set and the validation set (p > 0.05). After statistical analysis, it was found that whether there is invasion of the inferior vena cava, whether there is invasion of the hepatic artery, and whether there is metastasis to other organs are independent predictors of brain metastasis in HAE. A prediction model was built based on these three variables. The area under the ROC curve (AUC), cutoff value, sensitivity, and specificity of the training set and validation set were 0.922 and 0.886, 0.6934 and 0.6643, 75.00 and 84.62, 94.34 and 81.82, respectively. CRC shows good consistency between the predicted probability and the actual value of the sample. DCA showed that the clinical value of the model was high. CONCLUSION: The nomogram constructed based on imaging features combined with clinical indicators can effectively predict whether HAE will develop brain metastasis, which is helpful for clinicians to quickly screen out high-risk patients with HAE developing brain metastases, evaluate patient prognosis, and is more conducive to the realization of individualized and precise medical decisions.

The value of nomogram based on MRI functional imaging in differentiating cerebral alveolar echinococcosis from brain metastases.

OBJECTIVE: This study aims to evaluate the effectiveness of a nomogram model constructed using Diffusion Kurtosis Imaging (DKI) and 3D Arterial Spin Labeling (3D-ASL) functional imaging techniques in distinguishing between cerebral alveolar echinococcosis (CAE) and brain metastases (BM). METHODS: Prospectively collected were 24 cases (86 lesions) of patients diagnosed with CAE and 16 cases (69 lesions) of patients diagnosed with BM at the affiliated hospital of Qinghai University from 2018 to 2023, confirmed either pathologically or through comprehensive diagnosis. Both patient groups underwent DKI and 3D-ASL scanning. DKI parameters (Kmean, Dmean, FA, ADC) and cerebral blood flow (CBF) were analyzed for the parenchymal area, edema area, and symmetrical normal brain tissue area in both groups. There were 155 lesions in total in the two groups of patients. We used SPSS to randomly select 70% as the training set (108 lesions) and the remaining 30% as the test set (47 lesions) and performed a difference analysis between the two groups. The independent factors distinguishing CAE from BM were identified using univariate and multivariate logistic regression analyses. Based on these factors, a diagnostic model was constructed and expressed as a nomogram. RESULT: Univariate and multivariate logistic regression analyses identified nDmean1 and nCBF1 in the lesion parenchyma area, as well as nKmean2 and nDmean2 in the edema area, as independent factors for distinguishing CAE from BM. The model's performance, measured by the area under the ROC curve (AUC), had values of 0.942 and 0.989 for the training and test sets, respectively. Calibration curves demonstrated that the predicted probabilities were highly consistent with the actual values, and DCA confirmed the model's high clinical utility. CONCLUSION: The nomogram model, which incorporates DKI and 3D-ASL functional imaging, effectively distinguishes CAE from BM. It offers an intuitive, accurate, and non-invasive method for differentiation, thus providing valuable guidance for subsequent clinical decisions.

Comprehensive characterization of tumor therapeutic response with simultaneous mapping cell size, density, and transcytolemmal water exchange.

Early assessment of tumor therapeutic response is an important topic in precision medicine to optimize personalized treatment regimens and reduce unnecessary toxicity, cost, and delay. Although diffusion MRI (dMRI) has shown potential to address this need, its predictive accuracy is limited, likely due to its unspecific sensitivity to overall pathological changes. In this work, we propose a new quantitative dMRI-based method dubbed EXCHANGE (MRI of water Exchange, Confined and Hindered diffusion under Arbitrary Gradient waveform Encodings) for simultaneous mapping of cell size, cell density, and transcytolemmal water exchange. Such rich microstructural information comprehensively evaluates tumor pathologies at the cellular level. Validations using numerical simulations and in vitro cell experiments confirmed that the EXCHANGE method can accurately estimate mean cell size, density, and water exchange rate constants. The results from in vivo animal experiments show the potential of EXCHANGE for monitoring tumor treatment response. Finally, the EXCHANGE method was implemented in breast cancer patients with neoadjuvant chemotherapy, demonstrating its feasibility in assessing tumor therapeutic response in clinics. In summary, a new, quantitative dMRI-based EXCHANGE method was proposed to comprehensively characterize tumor microstructural properties at the cellular level, suggesting a unique means to monitor tumor treatment response in clinical practice.

Two-dimensional nanomaterials: A multifunctional approach for robust for diabetic wound repair.

Diabetic wounds pose a clinical challenge due to persistent inflammation, severe bacterial infections, inadequate vascularization, and pronounced oxidative stress. Current therapeutic modalities fail to provide satisfactory outcomes in managing these conditions, resulting in considerable patient distress. Two-dimensional nanomaterials (2DNMs), characterized by their unique nanosheet structures, expansive surface areas, and remarkable physicochemical properties, have garnered considerable attention for their potential in therapeutic applications. Emerging 2DNMs can be loaded with various pharmacological agents, including small molecules, metal ions, and liposomes. Moreover, they can be integrated with various biomaterials such as hydrogels, microneedles, and microspheres, thus demonstrating unprecedented advantages in expediting the healing process of diabetic wounds. Moreover, 2DNMs exhibit exceptional performance characteristics, including high biocompatibility, effective antimicrobial properties, optimal phototherapeutic effects, and enhanced electrostimulation capabilities. These properties enable them to modulate the wound microenvironment, leading to widespread application in tissue repair with remarkable outcomes. This review delineates several emerging 2DNMs, such as graphene and its derivatives, black phosphorus, MXenes, and transition metal dichalcogenides, in the context of diabetic wound repair. Furthermore, it elucidates the translational challenges and future perspectives of 2DNMs in wound healing treatments. Overall, 2DNMs present a highly promising strategy for ameliorating diabetic wounds, thus providing novel avenues for diagnostic and therapeutic strategies in diabetic wound management.

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.

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.

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.

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.

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.

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.

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.

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.

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.