Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases

BackgroundHepatic pedicle clamping is often required to reduce blood loss and transfusion during liver resection. However, the question remains whether use of hepatic pedicle clamping promotes tumor growth. Endothelial progenitor cells (EPCs) are mobilized from bone marrow in response to tissue ischemia, which allows neovascularization of ischemic tissue. It has been suggested that EPCs are involved in tumor progression. We hypothesized that hepatic ischemia reperfusion (I/R)-induced mobilization of EPCs could enhance growth of microscopic tumor, therefore promoting liver metastasis in a mouse model of colorectal cancer.Materials and methodsWe used mouse models of hepatic I/R and hind limb ischemia. For comparison, we studied mice that underwent limb ischemia as positive controls of EPC mobilization. At day 0, we divided 40 mice into four groups: hepatic I/R, hind limb ischemia, combined hepatic I/R and hind limb ischemia, and control (sham midline incision laparotomy). At day 2, we induced liver metastasis in all mice by injecting CT-26 cells into the spleen. Time-dependent circulating EPCs were determined by flow cytometry. We evaluated liver metastasis and microvascular density on day 21.ResultsThe number of circulating progenitor cells increased rapidly in the ischemic groups compared with the control group. Hepatic I/R significantly increased tumor outgrowth compared with the control group. Increased tumor growth was associated with enhanced CD31-positive microvascular density in liver tissue.ConclusionsHepatic I/R leads to mobilization of bone marrow–derived EPCs and enhanced intra-hepatic angiogenesis, which is associated with increased tumor burden in an animal model of colorectal liver metastasis.     

Update of the simplified criteria for autoimmune hepatitis: Evaluation of the methodology for immunoserological testing

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Association of weight-adjusted-waist index with all-cause and cardiovascular mortality in China: A prospective cohort study

Background and aimsAs a new simple anthropometric index, the weight-adjusted-waist index (WWI) appears to be superior to body mass index (BMI) and waist circumference (WC) in assessing both muscle and fat mass. We aimed to explore the association of WWI with all-cause and cardiovascular mortality in southern China.Methods and resultsA total of 12,447 participants (mean age, 59.0 ± 13.3 years; 40.6% men) in Jiangxi Province from the China Hypertension Survey study were included. WWI was defined as WC divided by the square root of weight. The outcome was all-cause and cardiovascular mortality. During a median follow-up of 5.6 years, 838 all-cause deaths occurred, with 390 cardiovascular deaths. Overall, there was a nonlinear positive relationship of WWI with all-cause and cardiovascular mortality. Accordingly, compared with participants in quartiles 1–3 (<11.2 cm/√kg), a significant higher risk of all-cause mortality (HR: 1.36, 95% CI: 1.17, 1.58) and cardiovascular mortality (HR: 1.43, 95% CI: 1.15, 1.77) were found in quartile 4 (≥11.2 cm/√kg). Further adjustment for BMI and WC did not substantially alter the results. No significant interactions were found in any of the subgroups (sex, age, area, physical activity, current smoking, current alcohol drinking, hypertension, and stroke).ConclusionHigher WWI levels (≥11.2 cm/√kg) were associated with increased the risk of all-cause and cardiovascular mortality in southern China. These findings, if confirmed by further studies, suggested that WWI may serve as a simple and effective anthropometric index in clinical practice.     

Immunohistochemical Determination of Hepatic Cytochrome P-4502E1 in Formalin-Fixed, Paraffin-Embedded Sections

Cytochrome P-4502E1 (2E1) is inducible by chronic ethanol consumption that results in enhanced activation of anesthetics and commonly used drugs (such as acetaminophen) to hepatotoxins. Therefore, assessment of hepatic 2E1 is needed in prescribing these drugs for the management of alcoholic patients. Currently, measurement of 2E1 requires either immunohistochemistry on frozen sections or Western blot (WB) analysis of homogenized tissue in excess of that needed for pathology. To obtain a more widely applicable method, we developed a procedure to detect 2E1 by immunohistochemistry in formalin-fixed, paraffin-embedded liver biopsies obtained routinely for diagnosis. Data were collected from rats fed ethanol-containing or control liquid diets for 3 weeks. lmmunostaining was performed using anti-human rabbit 2E1 antibody as the primary antibody, and the immunoreaction was detected by the avidin-biotin immunoperoxidase method after treating sections with target unmasking fluid, an antigen retrieval buffer that enhanced the staining of 2E1. In control rats, 2E1 staining was weak and perivenular. After ethanol feeding, it showed a lobular gradient, strongest perivenular and weakest periportal, similar to that seen in frozen sections. The staining intensity was scored as: 0 (no staining) to 3 (strong staining). The zonal staining was scored as follows: 1 = perivenular zonal staining, 2 = midzonal, and 3 = panlobular. With the product of the two scores, a significant difference was found between alcohol-fed and control rats (5.1 ± 0.3 vs. 0.8 ± 0.2, p < 0.001). 2E1 assessments by WB were also significantly different for these rat pairs (68.5 ± 2.1 vs. 7.9 ± 0.8 arbitrary units/mg protein, p < 0.001), with a parallel increase of immunostaining scores and WB measurement of 2E1 content. This immunohistochemical method was then validated in 14 paraffin-embedded percutaneous human liver biopsy samples. In livers of nonalcoholics, 2E1 staining was seen in the perivenular zone only, whereas in samples of alcoholics, the staining was perivenular to midzonal and sometimes periportal. A significant correlation between the zonal staining scores (r_s= 0.67, p < 0.005) or intensity ± zonal staining scores (r_s= 0.79, p < 0.001) and WB analysis was found. The immunohistochemical assessments of 2E1 expression in formalin-fixed, paraffin-embedded sections from livers of alcoholics was found to correlate with WB analysis, and lobular distribution was consistent with that seen in frozen sections. The proposed method should therefore be useful for the assessment of 2E1 content in paraffin-embedded liver samples, thereby aiding in the management of heavy drinkers.     

Screening for hypertension in young people with obesity: Feasibility in the real life

Background and aimScreening for pediatric hypertension (HTN) is based on several measurements of blood pressure (BP) in different visits. We aimed to assess its feasibility in outpatient youths with overweight/obesity (OW/OB) in terms of adherence to two-repeated measurements of BP and to show the features of youths who missed the follow-up and the predictive role of clinical and/or anamnestic features on confirmed HTN.Methods and resultsSix hundred, eighty-eight youths (9–17 years) with OW/OB, consecutively recruited, underwent a first measurement of BP. Those exhibiting BP levels within the hypertensive range were invited to repeat a second measurement within 1–2 weeks. Confirmed HTN was diagnosed when BP in the hypertensive range was confirmed at the second measurement. At entry, 174 youths (25.1%) were classified as hypertensive. At the second visit, 66 youths (37.9%) were lost to follow-up. In the remaining 108 participants, HTN was confirmed in 59, so that the prevalence of confirmed HTN was 9.5% in the overall sample; it was higher in adolescents than children (15.9% vs 6.8%, P = 0.001). HTN at first visit showed the best sensitivity (100%) and a good specificity (91%) for confirmed HTN. The association of HTN at first visit plus familial HTN showed high specificity (98%) and positive predictive value of 70%.ConclusionThe high drop-out rate confirms the real difficulty to obtain a complete diagnostic follow up in the obese population. Information about family history of HTN may assist pediatricians in identifying those children who are at higher risk of confirmed HTN.     

The prevalence of nonalcoholic fatty liver disease in Chinese adults screened by vibration controlled transient elastography and its diagnostic discrepancy compared with ultrasound

BackgroundThe prevalence of non-alcoholic fatty liver disease (NAFLD) in China as assessed using vibration-controlled transient elastography (VCTE) and its consistency with ultrasound is still unknown. We aimed to conduct a head-to-head comparison of consecutive measurements of NAFLD with ultrasound or VCTE to evaluate the discrepancy in the prevalence and distribution of NAFLD screened by two non-invasive techniques.MethodsWe collected VCTE and ultrasound examination data from 4,388 participants who underwent health check-ups at the Health Promotion Center of Jiangsu Province Hospital between January 2017 and December 2019. The major outcome was the presence of hepatic steatosis, which was defined as a median controlled attenuation parameter (CAP) ≥ 248 dB/m by VCTE or the definition of steatosis by ultrasound.ResultsAmong the 4,388 participants, 2,214 were diagnosed with NAFLD by VCTE (CAP ≥ 248 dB/m, 50.46%). Participants with severe steatosis (CAP ≥ 280 dB/m) were commonly male (77.94% vs. 50.38%, P < 0.001), were obese (45.09% vs. 1.79%, P < 0.001), had a worse metabolic profile, had elevated liver enzyme levels, and had advanced fibrosis. The prevalence of ultrasound-diagnosed NAFLD was 56.42%. After consistency analysis, VCTE and ultrasound showed moderate agreement regarding the diagnosis of NAFLD (κ = 0.475). We then compared the characteristics and clinical features of the four groups classified by the diagnosis results of the two techniques. NAFLD participants diagnosed by VCTE only were older, more obese, and had worse metabolic and biochemical profiles than NAFLD participants diagnosed by ultrasound only; in particular, the former had a higher proportion of abnormal alanine aminotransferase and aspartate aminotransferase levels and a higher proportion of advanced fibrosis than the latter.ConclusionsMore than half of Chinese adults were affected by NAFLD according to VCTE. Screening based on VCTE is more likely to identify NAFLD patients with severe clinical features than ultrasound. Therefore, VCTE is a more practical non-invasive tool for the screening and follow-up of NAFLD in China.     

酒精性肝病患者血浆白细胞介素-21水平及重组IL-21对LX-2肝星状细胞增殖和活化的影响

目的：分析酒精性肝病患者血浆白细胞介素-21（IL-21）水平及重组IL-21体外对LX-2肝星状细胞增殖和活化的影响。方法采用ELISA法检测17例酒精性肝炎、51例酒精性肝硬化患者和20例健康人血浆IL-21水平;体外培养LX-2肝星状细胞,以IL-21（1ng/ml或10ng/ml）处理24 h或48 h,检测LX-2细胞增殖及α-平滑肌肌动蛋白表达。结果与健康对照人群比,酒精性肝炎和酒精性肝硬化患者血浆IL-21水平均显著升高（P＆lt;0.05）,但酒精性肝炎和肝硬化患者之间无显著性差异,不同Child分级的肝硬化患者之间也无显著性差异;在IL-21作用24～48 h后,LX-2细胞增殖水平与对照组比无显著性差异,但α-平滑肌肌动蛋白表达均较对照组显著升高。结论血浆IL-21可能通过促进肝星状细胞活化参与了酒精性肝病患者肝纤维化的发生和发展。