Multiparametric MRI-based intratumoral and peritumoral radiomics for predicting the pathological differentiation of hepatocellular carcinoma.

PURPOSE: To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients. METHODS: A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC). RESULTS: Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively. CONCLUSIONS: Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation. CRITICAL RELEVANCE STATEMENT: Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation. KEY POINTS: • Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation. • The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models. • The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation.

Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome.

Objective: Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome). Methods: We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period. Results: Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated. Conclusion: Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

Mechanism of subchronic vinyl chloride exposure combined with a high-fat diet on hepatic steatosis.

Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid-induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800 mg/m3 ) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 µM) on hepatic steatosis of high-fat diet (HFD)-fed mice and palmitic acid (PA, 100 µM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single-exposure groups (HFD group, low-dose VC group, and high-dose VC group). Moreover, VC enhanced HFD-induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element-binding protein 1 (SREBP-1) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD-fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis-related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.

Relative Telomere Length in Peripheral Blood Cells and Hypertension Risk among Mine Workers: A Case-Control Study in Chinese Coal Miners.

Hypertension is a common chronic disease in middle-aged and elderly people and is an important risk factor for many cardiovascular diseases. Its pathogenesis remains unclear. Epidemiological studies have found that the loss of telomere length in peripheral blood cells can increase the risk of coronary heart disease, myocardial infarction, and other diseases. However, a correlation between loss of telomere length and hypertension has not been established. In this study, we aimed to explore the association between telomere length and the risk of essential hypertension (EH) in Chinese coal miners. A case-control study was performed with 215 EH patients and 222 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staff with the necessary medical knowledge. Relative telomere length (RTL) was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. In the control group, the age-adjusted RTL was statistically significantly lower in miners performing hard physical labour compared with nonphysical labour (P = 0.043). A significantly shorter age-adjusted RTL was found in the control group of participants who consumed alcohol regularly compared with those who do not consume alcohol (P = 0.024). Age-adjusted RTL was negatively correlated with body mass index (BMI) and alcohol consumption. Hypertension was also found to be significantly correlated with factors such as age, BMI, alcohol consumption, smoking, and tea consumption. Our results suggest that RTL is associated with hypertension in coal miners.

Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4+ T cell apoptosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe white matter demyelination. Because of its complex pathogenesis, there is no definite cure for MS. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties with several autoimmune diseases. It is also used to inhibit acute immune rejection due to its anti-inflammatory and immunosuppressive properties. However, it is unclear whether ATO has a therapeutic effect on EAE, and the underlying mechanisms have not yet been clearly elucidated. In this study, we attempted to assess whether ATO could be used to ameliorate EAE in mice. METHODS: ATO (0.5 mg/kg/day) was administered intraperitoneally to EAE mice 10 days post-immunization for 8 days. On day 22 post-immunization, the spinal cord, spleen, and blood were collected to analyze demyelination, inflammation, microglia activation, and the proportion of CD4+ T cells. In vitro, for mechanistic studies, CD4+ T cells were sorted from the spleen of naïve C57BL/6 mice and treated with ATO and then used for an apoptosis assay, JC-1 staining, imaging under a transmission electron microscope, and western blotting. RESULTS: ATO delayed the onset of EAE and alleviated the severity of EAE in mice. Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation, and decreased the expression levels of IL-2, IFN-γ, IL-1ß, IL-6, and TNF-α in EAE mice. Moreover, the number and proportion of CD4+ T cells in the spinal cord, spleen, and peripheral blood were reduced in ATO-treated EAE mice. Finally, ATO induced CD4+ T cell apoptosis via the mitochondrial pathway both in vitro and in vivo. Additionally, the administration of ATO had no adverse effect on the heart, liver, or kidney function, nor did it induce apoptosis in the spinal cord. CONCLUSIONS: Overall, our findings indicated that ATO plays a protective role in the initiation and progression of EAE and has the potential to be a novel drug in the treatment of MS.

[Effect of Different Adding Means of Ignited Water Purification Sludge on Phosphorus Adsorption and Forms].

The adsorption of external phosphorus (P) and the distribution of dissolved inorganic P (DIP) in the sediment interstitial water and sedimentary P forms were researched under the ignited water purification sludge (IWPS) addition (mixing and capping). The results showed that the adsorption ability of the IWPS increased obviously, compared with the water purification sludge (WPS). It indicated that the Smax increased by 43.7%, the EPC0 decreased by 69.1% and the DPS decreased by 54.4%. The contribution of P disappearance in the overlying water had almost no difference between the mixing and capping with IWPS, but it was obviously higher than the control in both cases. Under the mixing condition, the adsorption of external P by unit IWPS was 2.3 times of that under the capping condition, if the contacting probability between the IWPS and the overlying water was considered. Under the capping condition, the DIP in the sediment interstitial water (1-2 cm) was 33.17 times (average) of that under the mixing condition. It was attributed to the decrease of the dissolved oxygen penetration due to capping. Under the mixing condition, the external P tended to form Ca-P, while the percentages of NH4Cl-P and Fe/Al-P to Tot-P were bigger under the capping condition. It was suggested that the improvement of the sedimentary microenvironment by mixing with the IWPS was favorable for the adsorption of the external P and the immobilization of the internal P.

[External Phosphorus Adsorption and Immobility with the Addition of Ignited Water Purification Sludge].

The cumulative adsorption of external phosphorus (P) by water purification sludge after ignition under different addition methods (mix and cover) was investigated along with the adsorption isotherm and the release of internal P after external P adsorption. The cumulative adsorption of external P was 11.496 mg (mix) and 11.042 mg (cover) and these values were higher than those in the control (7.219 mg). The maximum sorption capacity (Smax) increased under the mix and cover and the former (7.795 mg·g-1) was higher than the latter (6.807 mg·g-1). However, the zero equilibrium P concentration (EPC0) in the mix was 0.83 mg·L-1, higher that in the cover (0.64 mg·L-1). The result suggests that the internal P was easily released in the mix method, compared to the cover method. Under anaerobic conditions, the release of the internal P was 0.93 mg in the mix, lower than that in the cover (1.49 mg) and in the control (7.76 mg). In addition, the specific release rate in the cover method was 0.00614 (mean), higher than that (0.00396) in the mix method. Noticeably, these data were lower than those in the control, indicating that the retention of P under the mix method was higher, compared to the cover and the control and it is challenging to evaluate the P retention with EPC0.

[Impacts of Multiple Disturbance on Migration and Transformation of Endogenous Phosphorus in Lake].

This work aimed to clarify the influence of multiple disturbance factors on the migration and transformation of endogenous phosphorus. In this experiment, the sediment of Meiliang Bay in Taihu Lake was studied as the major research object. With the help of Rhizon sampling technique, Unisense microelectrode system and so on, this experiment studied the change regularities of dissolved oxygen between sediment and water interface, different forms of phosphorus and iron ions under disturbance. The results indicated that the dissolved oxygen content in sediment decreased in the presence of Corbicula fluminea as compared with the control experiment. Disturbance made the peak area of DIP in interstitial water to migrate from 3-4 cm to 4-5 cm, which suggested that the "active region" of DIP regeneration went deeply into sediment with the appearance of Chironomus plumosus and Corbicula fluminea. Meanwhile, the existence of Corbicula fluminea and algae further reduced DIP in the interstitial water. That was because the released NH4Cl-P was transferred to phosphorus in overlying water and Fe/Al-P. With the increase of disturbance factors, the transformation ratio from NH4Cl-P to Fe/Al-P also increased gradually (from 44% to 59%).

Multi-slice spiral CT angiography in evaluating donors of living-related liver transplantation.

BACKGROUND: During the past years, the number of liver transplantation has increased greatly, but the number of available organs has not increased. In view of the critical shortage of organs, the indications for living-related liver transplantation (LRLT) have broadened since experience with the procedure has been achieved. This study was undertaken to assess the value of multi-slice spiral CT (MSCT) angiography in evaluating the hepatic arterial and veinous anatomy of potential donors for LRLT. METHODS: MSCT was performed after intravenous injection of contrast material at 3 ml/s. The total dose was calculated as 2 ml/kg. Twenty LRLT donors (2 men and 18 women) were subjected to MSCT angiography of hepatic blood vessels. These were generated by volume rendering and maximum intensity projection, while curved planar reformation was added in 5 patients. RESULTS: We identified 10 important hepatic vascular variants in 9 of the 20 donors (4 arterial, 4 venous, and 2 portal venous variants). In hepatic arterial variants, two had a replaced right hepatic artery arising from the superior mesenteric artery, an accessory right hepatic artery from the superior mesenteric artery and a replaced left hepatic artery arising from the left gastric artery. In hepatic venous variants, three had an accessory inferior right hepatic vein and one had two accessory inferior right hepatic veins. In hepatic portal venous variants, two had trifurcation of the main portal vein. CONCLUSIONS: As a non-invasive and reliable method, MSCT angiography is of value in the clinical evaluation of LRLT donors. MSCT angiography should be recommended as a routine preoperative examination for potential LRLT donors.