Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats

Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury.     

慢性肾脏病患者血清、尿液转化生长因子β1与肾功能的关系

目的 探讨血、尿TGF-β1在慢性肾脏病不同阶段的变化规律及临床意义.方法 2009年10月至2011年5月初诊的CKD患者40例,采用中国CKD患者资料校正的MDRD公式计算肾小球滤过率（eGFR）,按照eGFR水平随机分为5组,另设健康对照组8例.抽取受试者静脉血并分离血清,收集清洁中段尿,以酶联免疫法（ELISA）测定血、尿转化生长因子（TGF-β1）;全自动生化分析仪测量血肌酐（Scr）、尿素氮（BUN）,并观察TGF-β1与eGFR、Scr、BUN的关系.结果 在CKD 1~5期中,患者血清、尿液TGF-β1水平,除CKD 5期外,CKD 1～4期各测量值均较健康对照组明显增高,差异有统计学意义（P＜0.05）.CKD 1～4期各测量值逐渐升高,至CKD 5期反而下降,CKD 5期与CKD 1～4期差异有统计学意义（P＜0.05）.虽然CKD 1～4期均数逐渐升高,但是两两比较,差异无统计学意义（P＞0.05）.行Pearson相关分析显示,CKD 1～5期血清、尿液TGF-β1与eGFR呈负相关（r=-0.3037;r=-0.3384,P＜0.05）,与Scr、BUN无相关（P＞0.05）.结论 血、尿TGF-β1在CKD分布呈现一定的规律性,CKD 1～4期逐步升高,CKD 5期反而下降,说明血、尿TGF-β1可作为临床上反映肾纤维化程度的敏感指标,有助于客观评估肾纤维化水平,为抗肾纤维化的预防及治疗提供理论依据.     

矽肺模型大鼠血清中细胞因子消长规律的探讨

目的检测矽肺模型大鼠血清中细胞因子IL-1、IL-8、TNF-α、TGF-β的规律,探讨细胞因子在肺纤维化过程中的作用。方法 60只雄性Wistar大鼠随机分成对照组和实验组,每组30只;实验组经气管灌注1 ml游离二氧化硅粉尘悬液(100 mg/ml),对照组同法灌注等量生理盐水;分别于第1、7、14、21、28天,各组6只大鼠心脏取血,处死,并取肺组织。肺组织行HE染色,观察肺部炎症、纤维化等病理变化;酶联免疫吸附试验(ELISA)检测血清中IL-1、IL-8、TNF-α、TGF-β的含量。结果染尘大鼠血清IL-1含量均高于对照组,但不同时间,差别不明显;染尘第1、7、14天的IL-8含量均高于对照组,随着染尘时间增加,IL-8含量则渐回归正常;染尘第1、7天;TNF-α含量低于对照组;第14、21、28天TNF-α含量则高于对照组(P<0.05),染尘不同时间TNF-α含量也不同(F=30.724,P=0.001);血清TGF-β的波动则较明显,如染尘第1、7天其含量高于对照组,第14天则低于对照组,第21、28天又高于对照组(P<0.05),染尘不同时间的TGF-β含量也不同,差异具有统计学意义(F=33.236,P=0.001)。结论细胞因子IL-1、IL-8、TNF-α、TGF-β在染尘不同时间血清中的含量不同,其分泌的变化可能与染尘大鼠肺纤维化发生、发展有关。     

Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults: The Adverse Childhood Experiences (ACE) Study

Background: The relationship of health risk behavior and disease in adulthood to the breadth of exposure to childhood emotional, physical, or sexual abuse, and household dysfunction during childhood has not previously been described.Methods: A questionnaire about adverse childhood experiences was mailed to 13,494 adults who had completed a standardized medical evaluation at a large HMO; 9,508 (70.5%) responded. Seven categories of adverse childhood experiences were studied: psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned. The number of categories of these adverse childhood experiences was then compared to measures of adult risk behavior, health status, and disease. Logistic regression was used to adjust for effects of demographic factors on the association between the cumulative number of categories of childhood exposures (range: 0–7) and risk factors for the leading causes of death in adult life.Results: More than half of respondents reported at least one, and one-fourth reported ≥2 categories of childhood exposures. We found a graded relationship between the number of categories of childhood exposure and each of the adult health risk behaviors and diseases that were studied (P < .001). Persons who had experienced four or more categories of childhood exposure, compared to those who had experienced none, had 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold increase in smoking, poor self-rated health, ≥50 sexual intercourse partners, and sexually transmitted disease; and a 1.4- to 1.6-fold increase in physical inactivity and severe obesity. The number of categories of adverse childhood exposures showed a graded relationship to the presence of adult diseases including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease. The seven categories of adverse childhood experiences were strongly interrelated and persons with multiple categories of childhood exposure were likely to have multiple health risk factors later in life.Conclusions: We found a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.     

Indoor air pollutants in office environments: Assessment of comfort,health, and performance

Concentrations of volatile organic compounds (VOCs) in office environments are generally too low to cause sensory irritation in the eyes and airways on the basis of estimated thresholds for sensory irritation. Furthermore, effects in the lungs, e.g. inflammatory effects, have not been substantiated at indoor relevant concentrations. Some VOCs, including formaldehyde, in combination may under certain environmental and occupational conditions result in reported sensory irritation. The odour thresholds of several VOCs are low enough to influence the perceived air quality that result in a number of acute effects from reported sensory irritation in eyes and airways and deterioration of performance. The odour perception (air quality) depends on a number of factors that may influence the odour impact. There is neither clear indication that office dust particles may cause sensory effects, even not particles spiked with glucans, aldehydes or phthalates, nor lung effects; some inflammatory effects may be observed among asthmatics. Ozone-initiated terpene reaction products may be of concern in ozone-enriched environments (≥0.1 mg/m³) and elevated limonene concentrations, partly due to the production of formaldehyde. Ambient particles may cause cardio-pulmonary effects, especially in susceptible people (e.g. elderly and sick people); even, short-term effects, e.g. from traffic emission and candle smoke may possibly have modulating and delayed effects on the heart, but otherwise adverse effects in the airways and lung functions have not been observed. Secondary organic aerosols generated in indoor ozone-initiated terpene reactions appear not to cause adverse effects in the airways; rather the gaseous products are relevant. Combined exposure to particles and ozone may evoke effects in subgroups of asthmatics.     

Safety and efficacy of recombinant and live herpes zoster vaccines for prevention in at-risk adults with chronic diseases and immunocompromising conditions

Compared with the general population, older adults with immune senescence and individuals who are immunocompromised (IC) due to disease or immunosuppressive therapy are at increased risk for herpes zoster (HZ) and its associated complications, which can be debilitating and life-threatening. Vaccination can be an effective strategy against HZ and studies have shown that HZ vaccination in IC individuals can elicit immune responses and provide protection from infection. Recently, the first approvals have been granted in the United States and the European Union for the recombinant HZ vaccine (RZV) in adults ≥ 18 years of age at risk of HZ due to immunodeficiency or immunosuppression. Existing systematic reviews have highlighted the risks for HZ in limited immunocompromising conditions and have only examined clinical data for RZV. This review details the risks and burden of HZ in a broad range of clinically relevant IC populations and summarizes key efficacy and safety data for RZV and live HZ vaccine in these individuals. Research has shown IC individuals can benefit from HZ vaccination; however, these insights have yet to be fully incorporated into vaccination guidelines and clinical care. Clinicians should consider HZ vaccination in eligible at-risk populations to protect against HZ and its associated complications and thereby, reduce the burden that HZ poses on the healthcare system. Electronic health records and linked personal health records could be used to identify and contact patients eligible for HZ vaccination and provide clinical decision support-generated alerts for missing or delayed vaccinations. This review will help clinicians identify eligible IC individuals who may benefit from HZ vaccination.A video abstract linked to this article is available on Figshare https://doi.org/10.6084/m9.figshare.21517605.