Current understandings and perspectives on non-cancer health effects of benzene: A global concern

Objective

Benzene, as a volatile organic compound, is known as one of the main air pollutants in the environment. The aim of this review is to summarize all available evidences on non-cancerous health effects of benzene providing an overview of possible association of exposure to benzene with human chronic diseases, specially, in those regions of the world where benzene concentration is being poorly monitored.

Methodology

A bibliographic search of scientific databases including PubMed, Google Scholar, and Scirus was conducted with key words of “benzene toxic health effects”, “environmental volatile organic compounds”, “diabetes mellitus and environmental pollutants”, “breast cancer and environmental pollution”, “prevalence of lung cancer”, and “diabetes prevalence”. More than 300 peer reviewed papers were examined. Experimental and epidemiologic studies reporting health effects of benzene and volatile organic compounds were included in the study.

Results

Epidemiologic and experimental studies suggest that benzene exposure can lead to numerous non-cancerous health effects associated with functional aberration of vital systems in the body like reproductive, immune, nervous, endocrine, cardiovascular, and respiratory.

Conclusion

Chronic diseases have become a health burden of global dimension with special emphasis in regions with poor monitoring over contents of benzene in petrochemicals. Benzene is a well known carcinogen of blood and its components, but the concern of benzene exposure is more than carcinogenicity of blood components and should be evaluated in both epidemiologic and experimental studies. Aspect of interactions and mechanism of toxicity in relation to human general health problems especially endocrine disturbances with particular reference to diabetes, breast and lung cancers should be followed up.     

Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice

Osteopontin (OPN) is a chemotactic factor which can be cleaved to the pro-inflammatory form by matrix metalloproteinases (MMPs). To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL). OPN-KO mice showed significant reduction in liver injury (plasma ALT and necrosis) and neutrophil recruitment compared with WT animals at 24 h but not 72 h after BDL. In WT mice, a 4-fold increase in hepatic MMP-3 mRNA and elevated MMP activities and cleaved OPN levels were observed in bile. WT mice subjected to BDL in the presence of the MMP inhibitor BB-94 showed reduced liver injury, less neutrophil extravasation and diminished levels of cleaved OPN in bile. Thus, during obstructive cholestasis, OPN released from biliary epithelial cells could be cleaved by MMPs in bile. When the biliary system leaks, cleaved OPN enters the parenchyma and attracts neutrophils. In the absence of OPN, other chemoattractants, e.g. chemokines, mediate a delayed inflammatory response and injury. Taken together, our data suggest that OPN is the pro-inflammatory mediator that initiates the early neutrophil-mediated injury phase during obstructive cholestasis in mice.     

健康查体者体重指数与肝酶及脂肪肝关系的探讨

目的：探讨健康查体者体重指数（BMI）与肝酶及脂肪肝的关系。方法选取笔者所在医院2014年1~5月的107例健康查体者,测量其身高、体重、肝功能,行肝脏彩超检查。根据BMI进行分组,对每组肝酶及脂肪肝情况进行分析。结果3组肝酶指标比较显示仅超重者和肥胖者ALT、GGT与正常组的ALT、GGT比较差异有统计学意义,其余指标比较差异无统计学意义;3组脂肪肝患者的情况比较差异均有统计学意义。结论超重者和肥胖者的ALT、GGT与正常组比较均升高,其余指标比较无异常,对于因肥胖导致的脂肪肝,ALT及GGT变化最早、最敏感,随着体重指数的增加,脂肪肝患病率越来越高,脂肪肝程度越来越严重。     

Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B

Introduction and ObjectivesHepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB.Patients and MethodsPatients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models.ResultsSixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study.ConclusionAlthough it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.     

FibroScan行肝脏硬度检测和APRI评估慢性丙型肝炎患者肝纤维化程度价值比较*

目的 探讨使用FibroScan行肝脏硬度检测(LSM)和应用门冬氨酸氨基转移酶/血小板比值(APRI)评估慢性丙型肝炎(CHC)患者肝纤维化程度的价值。方法 2016年5月～2020年5月我院收治的CHC患者133例和同期健康体检者133名,接受FibroScan检查及血生化和血液检查,计算APRI。CHC患者接受肝穿刺活检。结果 CHC患者LSM和APRI分别为(10.3±4.2)和(0.8±0.3),显著高于健康人【分别为(4.3±2.0)和(0.3±0.1),P＜0.05】;52例S₁期患者LSM和APRI分别为(6.5±2.4)和(0.6±0.2),37例S₂期患者LSM和APRI分别为(10.3±2.9)和(0.9±0.3),28例S₃期患者LSM和APRI分别为(14.5±4.1)和(1.2±0.5),16例S₄期患者LSM和APRI分别为(18.4±5.7)和(1.8±0.6),相差显著(P＜0.05);经ROC分析LSM预测CHC患者显著肝纤维化(大于等于S2)的曲线下面积(AUC)为0.891,标准误为0.033,P=0.000,95%可信区间为0.826～0.956,最佳截断点为11.200,其诊断的敏感度为0.625,特异度为0.925,而APRI预测CHC患者显著肝纤维化的AUC为0.776,标准误为0.050,P=0.000,95%可信区间为0.678～0.875,最佳截断点为0.795,其敏感度为0.643,特异度为0.887;经相关性分析发现,LSM和APRI与CHC患者肝纤维化程度呈正相关(P＜0.05)。结论 应用LSM和APRI评估CHC患者肝纤维化程度有一定的临床价值,特别是对于存在显著肝纤维化的患者,可早期作出病情判断,对指导临床处理有很大的帮助,值得进一步研究。     

Single-centre retrospective observational study comparing trough blood concentration and safety of teicoplanin formulations

Teicoplanin formulations are marketed as antibiotic mixtures with several compounds that share the same core structure. Recent studies conducted in vitro have reported differences in the composition ratio of different teicoplanin products. In this retrospective study, we examined the trough blood concentration of the originator brand and a generic teicoplanin product. Target patients were retrospectively assigned to the originator (Targocid) or generic group. The groups were matched 1:1 using propensity scores. The initial trough blood concentration analysis identified 44 matches. In both groups, the median dosing day for the first measurements was 4, respectively. The initial trough blood concentration of the originator group was significantly higher (mean ± SD, 16.3 ± 4.5 mg/L) than that of the generic group (12.8 ± 4.7 mg/L; 95% CI, ?5.4 to ?1.6). A significant difference was observed in the frequency of serum creatinine elevation in the study of the frequency of adverse events using Common Terminology Criteria for Adverse Events (originator group, 41.9% vs generic group, 20.9%). In cases where discontinuation was necessary due to side effects, there were three patients in the originator group and one patient in the generic group. This study found that trough blood concentration differed between formulations. Therefore, correction might be necessary while monitoring drug concentration in the blood. Trough blood concentrations are used as surrogate markers for efficacy and safety, so further studies on differences in efficacy and safety between formulations are required.     

乙型肝炎e抗原阴性慢性乙型肝炎和肝硬化患者病毒基因型及丙氨酸氨基转移酶水平分析

目的观察乙型肝炎e抗原(HBeAg)阴性慢性乙型肝炎(CHB)及肝硬化患者的乙型肝炎病毒(HBV)基因型及丙氨酸氨基转移酶(ALT)水平。方法采用酶联免疫吸附法检测62例CHB和41例肝硬化患者HBV标志物和血清ALT水平,用聚合酶链反应法检测其HBV基因型。结果CHB患者中,21 例(33.9%)为HBeAg阴性,41例(66.1%)为HBeAg阳性;肝硬化患者中,28例(68.3%)为HBeAg阴性,13例(31.7%)为HBeAg阳性。CHB患者中,53例(85.5%)为C基因型,9例(14.5%)为B基因型; 肝硬化患者中39例(95.1%)为C基因型,2例(4.9%)为B基因型。HBeAg阴性CHB患者ALT>40 U/L 者的比例低于HBeAg阳性组(分别为47.6%和85.4%),差异有统计学意义(P<0.01)。HBeAg阴性肝硬化患者ALT>40 U/L者的比例低于HBeAg阳性组(分别为64.3%和92.3%)但差异无统计学意义。结论CHB 和肝硬化患者中,HBeAg阴性者的比例较高,此类患者的ALT水平较低,以C基因型占优势。     

2型糖尿病患者血清肝酶谱与甲状腺激素和中国人内脏脂肪指数的关系

目的探讨2型糖尿病患者血清肝酶谱与甲状腺激素和中国人内脏脂肪指数(Chinese visceral adipose index,CVAI)的关系,分析影响肝酶的因素。方法选取700例于本院内分泌科住院的2型糖尿病患者,根据肝酶是否升高分为肝酶升高组和肝酶正常组,再将丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰胺转肽酶(GGT)分别进行三等分分组。比较2组间及ALT、AST、GGT三等分分组间甲状腺激素和CVAI的差异,分析ALT、AST、GGT与甲状腺激素和CVAI的相关性。结果肝酶升高组较肝酶正常组T4、CVAI升高(P<0.05)。随着ALT、AST的升高,FT3、T3、T4逐渐升高(P<0.05);随着ALT、GGT的升高,CVAI也逐渐升高(P<0.05)。相关性分析显示,ALT、AST与FT3、T3、T4呈正相关;ALT、GGT与CVAI呈正相关;CVAI与FT3、T3呈正相关;HbA1C与FT3、T3和T4呈负相关。回归分析显示,FT3、CVAI和HbA1C是ALT的影响因素,T4是AST的影响因素,T3和HbA1C是GGT的影响因素。结论2型糖尿病患者中甲状腺激素和CVAI与肝酶水平均有一定相关性。