Neoadjuvant chemotherapy for patients with resectable colorectal cancer liver metastases: A systematic review and meta-analysis

BACKGROUNDIn recent years, neoadjuvant chemotherapy (NAC) has been increasingly used in patients with resectable colorectal liver metastases. However, the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases (CRLM) are still controversial.AIMTo assess the efficacy and application value of NAC in patients with resectable CRLM.METHODSWe searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC. Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software. RESULTSIn total, 32 studies involving 11236 patients were included in this analysis. We divided the patients into two groups, the NAC group (that received neoadjuvant chemotherapy) and the non-NAC group (that received no neoadjuvant chemotherapy). The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were HR = 0.49, 95%CI: 0.39-0.61, P = 0.000 and HR = 0.48 95%CI: 0.36-0.63, P = 0.000. The duration of surgery in the NAC group was longer than that of the non-NAC group [standardized mean difference (SMD) = 0.41, 95%CI: 0.01-0.82, P = 0.044)]. The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group (SMD = 0.73, 95%CI: 0.02-1.43, P = 0.043). The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group (SMD = 1.24, 95%CI: 1.07-1.43, P = 0.004).CONCLUSIONWe found that NAC could improve the long-term prognosis of patients with resectable CRLM. At the same time, the NAC group did not increase the risk of any adverse event compared to the non-NAC group.     

Computed Tomography Measurements of Hepatic Steatosis in Cholelitihiasis and Cholecystectomy Cases Using Unenhanced Images

IntroductionComputed tomography (CT) measurements of hepatic steatosis can be performed using unenhanced CT images. The purpose of this study was to assess the occurrence of hepatic steatosis using unenhanced CT images for patients undergoing cholecystectomy or having cholelithiasis.MethodsA total of 143 unenhanced CT cases from a single centre were retrospectively examined. The CT number of liver, ratio of CT number of liver to spleen, and CT number of liver minus CT number of spleen were measured in three groups: (1) patients undergoing cholecystectomy, (2) patients having cholelithiasis, and (3) control group. Abdominal circumference, anterior subcutaneous fat tissue thickness, and body mass index were obtained.ResultsMean CT number of liver was significantly different between the group of patients with cholecystectomy and cholelithiasis and the control group (P < .001) and also between cases of cholecystectomy and cholelithiasis (P = .041), with the lowest CT number of liver in the cholecystectomy group. The mean CT number of liver minus CT number of spleen and mean CT number (liver/spleen) ratios, evaluated separately for both lobes, were not different comparing the cholelithiasis and cholecystectomy groups. The mean CT number of liver minus CT number of spleen and mean CT number (liver/spleen) ratios differed significantly between the control group and both patient groups (P < .001). Positive correlations were identified between abdominal circumference, subcutaneous fat depth, body mass index, and liver size and hepatic steatosis.ConclusionThere was an increased occurrence of hepatic steatosis in patients who have undergone a cholecystectomy compared with patients treated for cholelithiasis and the control group.     

N-Acetylcysteine ameliorates the late phase of liver ischaemia/reperfusion injury in the rabbit with hepatic steatosis

Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the aim of the present study was to evaluate the in vivo effect of NAC (N-acetylcysteine) on hepatic function in the early and initial late phase of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits were fed a high-cholesterol (2%) diet. The control group (n=6) underwent lobar liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group receiving NAC (n=6), an intravenous infusion of NAC was administered prior to and during the 6 h reperfusion period. Systemic and hepatic haemodynamics were monitored continuously. ALT (alanine aminotransferase) activity and bile production were measured. NMR spectroscopy was used to analyse bile composition. Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of production of reactive oxygen and nitrogen species. Moderate centrilobular hepatic steatosis was demonstrated by histology. The results showed that NAC administration significantly improved portal flow, hepatic microcirculation, bile composition and bile flow after 5 h of reperfusion. NAC administration was also associated with less hepatocellular injury, as indicated by ALT serum activity, and decreased the oxidation of DHR to RH. In conclusion, NAC administration decreased the extent of I/R injury in the steatotic liver, particularly during the late phase of reperfusion.     

深圳市中高层职业人群腰臀比值、体重指数与脂肪肝的相关性研究

目的探讨深圳市中高层职业人群腰臀比值、体重指数与肥胖、高脂血症、脂肪肝等的相关性及流行病学特征。方法对2004年9月~2005年8月深圳市企事业单位中高层职业人群1515例健康体检者进行身高、体重、腰围、臀围、腹部B超、血脂等检测,并按腰臀比值、体重分层分析各组与肥胖、高脂血症脂肪肝等的相关性及流行病学特征。结果受检者肥胖患病率为27.9%,超重者患病率为21.6%,中心性肥胖患病率为24.8%。高脂血症患病率为55.25%(男性63.89%,女性39.78%),脂肪肝患病率为21.19%(男性28.09%,女性8.84%)。中心性肥胖组(按WHR分型)和外周型肥胖组(按BMI分型)的高脂血症、脂肪肝的检出率明显高于正常体型和正常体重组(P<0.01)。中心性肥胖的高脂血症、脂肪肝患病率的检出率明显高于外周肥胖(P<0.01)。中心性肥胖与外周肥胖都与高脂血症、脂肪肝的患病率呈正相关(P<0.01)。结论深圳市中高层职业人群肥胖、高脂血症和脂肪肝的患病率明显增高,尤其是高脂血症值得关注。肥胖、高脂血症是导致脂肪肝的独立危险因素,中心性肥胖比外周型肥胖危险性更大。腰臀比值与体重指数都可作为脂肪肝的危险预测因素,腰臀比值比体重指数特异性更高,两者结合进行可明显提高脂肪肝风险预测的特异性和敏感性。     

肝脂肪变性促进慢性丙型肝炎病程进展的研究

目的 研究脂肪变性在慢性丙型肝炎疾病进程中的作用.方法 收集治疗前行肝穿刺病理检查的慢性丙型肝炎患者159例,按照感染HCV基因亚型分为基因1b型组、基因2a型组和其他基因型组,荧光定量PCR法检测所有病例血清HCV载量,组织学评估各组穿刺肝组织炎症坏死、纤维化和肝细胞脂肪变性程度.结果 HCV基因1b型和2a型感染患者占总病例的65.41%,63.52%(101/159)的慢性丙型肝炎患者发生肝细胞脂肪变性,不同基因型组间脂肪变性程度无统计学差异.不同基因型组HCV慢性感染者间炎症活动度、纤维化程度和脂肪变性程度无统计学差异(P均>0.05).肝脂肪变性与肝纤维化和炎症活动度均密切相关(r值分别为0.34和0.29,P均<0.01),但HCV感染病毒量与脂肪变性、肝纤维化和炎症活动度间无明显相关性.结论 脂肪变性促进慢性丙型肝炎病程进展.     

超声衰减成像技术评价肝脂肪变性的相关因素分析

目的探讨影响超声衰减系数（AC）变化的相关因素,并评估衰减成像（ATI）技术对非酒精性脂肪性肝病（NAFLD）定量诊断的临床实用性及测量的可重复性。 方法选取2019年9月至2020年12月在哈尔滨医科大学附属第一医院使用超声的ATI技术进行肝检测的114例受试者（NAFLD组56例,健康对照组58例）,分别获得二维超声和AC,同时收集患者相应的临床资料、血生化检测指标等,通过多因素线性回归分析确定AC的独立影响因素。使用常规二维超声检查对所有研究对象的肝脂肪变性程度进行四分制评分（S0~S3组）,采用方差分析检验各组间AC的差异性,使用Spearman相关分析方法评估AC与肝脂肪变性程度的相关性,并计算组内相关系数（ICC）,评估2名操作者间（AC-1组和AC-2组）ATI测量的可重复性。 结果多因素线性回归分析显示体质量指数（BMI）、肝脂肪变性程度是AC的独立影响因素（β=0.007,95%CI：0.001~0.013,P=0.017;β=0.083,95%CI：0.070~0.095,P＜0.001）。NAFLD组AC显著高于健康对照组［AC-1组：（0.716±0.098）dB/（cm·MHz）vs（0.539±0.058）dB/（cm·MHz）;AC-2组：（0.699±0.102）dB/（cm·MHz）vs（0.542±0.053）dB/（cm·MHz）］,且随着肝脂肪变性程度的加重,AC逐渐升高［S0组（58例）AC为（0.539±0.058）dB/（cm·MHz）,S1组（23例）AC为（0.640±0.063）dB/（cm·MHz）,S2组（20例）AC为（0.718±0.050）dB/（cm·MHz）,S3组（13例）AC为（0.845±0.059）dB/（cm·MHz）;F=122.27,P＜0.001］。AC与肝脂肪变性程度存在较强的相关性（r=0.840;P＜0.001）。不同肝脂肪变性程度AC的组内相关系数（ICC）分别为0.816（95%CI：0.708~0.881）、0.886（95%CI：0.301~0.967）、0.876（95%CI：0.479~0.960）、0.939（95%CI：0.819~0.981）,P均＜0.001。 结论AC与BMI、肝脂肪变性程度显著相关,且ATI技术的操作者间可重复性极好,结果较为稳定,有助于早期发现脂肪肝并对脂肪肝严重程度进行评估。     

Pharmacokinetics of enalapril and metoprolol in hypertensive patients with hepatic pathology

AIM: To examine characteristics of pharmacokinetics and pharmacodynamics of enalapril and metoprolol in hypertensive patients with gastrointestinal diseases to make relevant corrections in the treatment. MATERIAL AND METHODS: The study included 36 hypertensive patients with steatosis, hepatic cirrhosis and ulcer. All the patients received metoprolol or enalapril. Concentrations of metoprolol and enalaprilate (active enalapril metabolite) were determined with high performace liquid chromatography. The findings gave grounds for calculation of mean drug retention time (MRT) and area under curve "concentration-time" (AUC). Efficacy of the drugs was estimated by the data of 24-h blood pressure monitoring. RESULTS: Hypertensive patients with hepatic diseases given enalapril exhibited lowering of maximal concentration (C(max)) of enalaprilate and prolongation of time of its reaching (T(max)) compared to ulcer patients. MRT and AUC were increased in hepatic cirrhosis patients treated with enalapril and metoprolol. Metoprolol C(max) in this group of patients was higher than in the controls. Blood pressure monitoring showed that enalapril therapy was more effective in ulcer patients vs patients with liver diseases. Metoprolol treatment of hypertensive patients with hepatic cirrhosis resulted in development of bradycardia. CONCLUSION: In hypertensive patients with liver diseases on enalapril therapy its metabolite production may appear insufficient for therapeutic effect and higher dose may be needed. Metoprolol in the treatment of hypertensive patients with hepatic cirrhosis should be used with caution because of disturbance of its metabolism and possible cumulative effects.     

Efficacy of activated charcoal administered more than four hours after acetaminophen overdose

To evaluate whether administration of activated charcoal, in addition to standard N-acetylcysteine (NAC) therapy, after acetaminophen overdose provides additional patient benefit over NAC therapy alone, a 1-year non-randomized prospective, multi-center, observational case series was performed at three poison centers and one poison center system. Entrance criteria were all acute acetaminophen overdoses with: 1) an acetaminophen blood concentration determined to be in the toxic range by the Rumack-Matthew nomogram; and 2) all therapies, including NAC and activated charcoal, initiated between 4 and 16 h post-ingestion. There were 145 patients meeting entrance criteria, of whom 58 patients (40%) received NAC only and 87 patients (60%) received NAC and activated charcoal. Overall, 23 patients had elevations of AST or ALT greater than 1000 IU/L, of which 21 patients received NAC only (38% of total NAC only group) and 2 patients received NAC and activated charcoal (2% of total NAC+AC group). Administration of activated charcoal in this series of patients with toxic acetaminophen concentrations treated with NAC was associated with reduced incidence of liver injury, as measured by elevated serum transaminases and prothrombin times.     

应用双氯芬酸钠后骨质疏松性骨折大鼠的肝肾变化:组织学验证

背景:临床上常用非类固醇类抗炎药治疗骨质疏松症和骨质疏松性骨折引起的疼痛,文献报道非类固醇类抗炎药会引起肝肾功能的损害,但其究竟如何影响肝肾组织尚不清楚.目的:观察双氯芬酸钠对骨质疏松性骨折大鼠肝肾组织的影响.设计、时间及地点:随机对照动物实验,于2007-08/2008-02在上海中医药大学动物实验中心完成.材料:8月龄雌性SD大鼠24只,体质量300-320 g,随机分为生理盐水组、双氯芬酸钠先骨折后药物组和双氯芬酸钠先药物后骨折组,每组8只.方法:大鼠卵巢去势后饲养3个月,建立骨质疏松模型,随机分组.生理盐水组和先骨折后药物组先进行双侧股骨中段骨折造模,再分别灌注生理盐水10 mL/(kg·d)和双氯芬酸钠5 mg/(kg·d).1次/d,共3周;先药物后骨折组先灌注双氯芬酸钠5 mg/(kg·d)3周,再进行骨折造模.主要观察指标:分别于骨折后2,3,4,6周摘取肝脏和双侧肾脏,行苏木精-伊红染色观察.各组大鼠肝脏和肾脏组织学观察.结果:双氯芬酸钠先骨折后药物组肾小球炎症反应;肾小管管腔扩张,上皮细胞水肿,细胞核消失,小管变性坏死,管腔内出现白细胞及细胞碎片和药物结晶;肾间质充血,炎症细胞浸润.双氯芬酸钠组肝小叶结构模糊,肝细胞肿胀,脂肪变性,部分肝细胞坏死:汇管区炎症反应;中央静脉和肝窦隙淤血.双氯芬酸钠先药物后骨折组同样造成肝肾组织损害,持续3周左右.结论:双氯芬酸钠对骨质疏松性大鼠的肝肾组织有一定损害,尤其是肾脏组织.长时间应用双氯芬酸钠造成的肝肾组织损害是不可逆的.     

磁共振扩散加权成像评估乳腺癌新辅助化疗疗效

目的 探讨MR DWI评估乳腺癌新辅助化疗(NAC)疗效的价值。方法 对36例经穿刺病理证实的乳腺癌患者在NAC前、后不同疗程末行DWI。依据手术病理结果分为有效组和无效组,比较有效组和无效组化疗前ADC值的差异及化疗前、后不同疗程肿瘤ADC值的差异。结果 36例中,有效组(24例)化疗前肿瘤平均ADC值为(0.98±0.18)×10^-3 mm²/s,无效组(12例)化疗前肿瘤平均ADC值为(0.95±0.15)×10^-3 mm²/s(t＝0.694,P＝0.411)。有效组化疗后ADC值升高,化疗前肿瘤ADC值与化疗第2~8个疗程后比较差异均有统计学意义;无效组化疗前、后肿瘤ADC值差异无统计学意义。有效组化疗前20例患者的对侧正常乳腺组织平均ADC值为(1.98±0.30)×10^-3 mm²/s,化疗4个疗程后12例患者的对侧正常乳腺组织平均ADC值为(1.96±0.28)×10^-3 mm²/s,差异无统计学意义。结论 化疗有效组乳腺癌ADC值较化疗前升高;根据ADC值可以早期预测乳腺癌NAC疗效。     

Ultrasound Detection of Liver Fibrosis in Individuals with Hepatic Steatosis Using the Homodyned K Distribution

Acoustic structure quantification (ASQ) based on the analysis of ultrasound backscattered statistics has been reported to detect liver fibrosis without significant hepatic steatosis. This study proposed using ultrasound parametric imaging based on the parameter α of the homodyned K (HK) distribution for staging liver fibrosis in patients with significant hepatic steatosis. Raw ultrasound image data were acquired from patients (n = 237) to construct B-mode and HK α parametric images, which were compared with the focal disturbance (FD) ratio obtained from ASQ on the basis of histologic evidence (METAVIR fibrosis score and hepatic steatosis severity). The data were divided into group I (n = 173; normal to mild hepatic steatosis) and group II (n = 64; with moderate to severe hepatic steatosis) for statistical analysis through one-way analysis of variance and receiver operating characteristic (ROC) curve analysis. The results showed that the HK α parameter monotonically decreased as the liver fibrosis stage increased (p < .05); concurrently, the FD ratio increased (p < .05). For group I, the areas under the ROC (AUROCs) obtained using the FD ratio and the α parameter (AUROC_FD and AUROC_α) were, respectively, 0.56 and 0.55, 0.68 and 0.68, 0.64 and 0.64 and 0.62 and 0.62 for diagnosing liver fibrosis ≥F1, ≥F2, ≥F3 and ≥F4. The values of AUROC_FD and AUROC_α for group II were, respectively, 0.88 and 0.91, 0.81 and 0.81, 0.77 and 0.76 and 0.78 and 0.73 for diagnosing liver fibrosis ≥F1, ≥F2, ≥F3 and ≥F4. As opposed to previous studies, ASQ was found to fail in characterizing liver fibrosis in group I; however, it was workable for identifying liver fibrosis in patients with significant hepatic steatosis (group II). Compared with ASQ, HK imaging provided improved diagnostic performance in the early detection of liver fibrosis coexisting with moderate to severe hepatic steatosis. Ultrasound HK imaging is recommended as a strategy to evaluate early fibrosis risk in patients with significant hepatic steatosis.     

肝脏脂肪变性对肝切除术后并发症的影响

目的：探讨肝脏脂肪变性对肝脏切除手术后并发症的影响。方法：回顾总结270例肝癌肝切除患者的临床及病理资料,对其相关指标等进行统计学分析。结果：270例患者有60例伴有肝脏脂肪变性,其中轻度脂肪变性35例,中重度脂肪变性25例。脂肪变性组年龄高于对照组（P〈0.05）,肥胖患者比例也明显较高（P〈0.01）,体质量指数明显高于对照组患者（P〈0.01）,且术后前白蛋白降低幅度高于对照组（P〈0.05）。各组间术后并发症总发生率无统计学意义,但中重度脂肪变性组术后需临床治疗的并发症发生率高于对照组（P〈0.05）。结论：肝脏脂肪变性是导致肝切除术后需要临床治疗并发症的独立危险因素。     

硫普罗宁对合并乙型肝炎的肺结核患者抗痨治疗时保肝作用的观察

目的：观察硫普罗宁对合并乙型肝炎的肺结核患者在抗痨治疗时的保肝作用。方法：42例合并乙型肝炎的初治涂阳肺结核患者，随机分为两组。治疗组22例在抗痨治疗的同时给予硫普罗宁片治疗，对照组20例在抗痨治疗的同时给予肌苷片或肝泰乐片等一般保肝药物。结果：治疗组治疗前后肝功能无变化，对照组治疗1个月后AST、ALT、BIL明显升高。结论：硫普罗宁可保护肝细胞，增加对抗结核药物耐受性。     

Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats

Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.     

Comparison of S-Adenosyl-L-methionine and N-acetylcysteine protective effects on acetaminophen hepatic toxicity

Nutraceuticals are widely used by the general public, but very little information is available regarding the effects of nutritional agents on drug toxicity. Excessive doses of acetaminophen (APAP, 4-hydroxyacetanilide) induce hepatic centrilobular necrosis. The naturally occurring substance S-adenosyl-l-methionine (SAMe) has been reported to reduce the hepatic toxicity of APAP. The present study was designed to investigate the hepatoprotective effects of SAMe in comparison to the clinically used antidote N-acetylcysteine (NAC). Male C57BL/6 mice were injected intraperitoneally (i.p.) with an equimolar dose (1.25 mmol/kg) of either SAMe or NAC just before APAP, and the groups were denoted SAMe+APAP and NAC+APAP, respectively. Mice were immediately injected i.p. with 300 mg/kg APAP, and hepatotoxicity was evaluated after 4 h. SAMe was more hepatoprotective than NAC at a dose of 1.25 mmol/kg as liver weight was unchanged by APAP injection in the SAMe+APAP group, whereas liver weight was increased in the NAC+APAP group. SAMe was more hepatoprotective for APAP toxicity than NAC, because alanine aminotransferase levels were lower in the SAMe+APAP. Pretreatment with SAMe maintained total hepatic glutathione (GSH) levels higher than NAC pretreatment before APAP, although total hepatic GSH levels were lower in the SAMe+APAP and NAC+APAP groups than the vehicle control values. Oxidative stress was less extensive in the SAMe+APAP group compared with the APAP-treated mice as indicated by Western blots for protein carbonyls and 4-hydroxynonenal-adducted proteins. In summary, SAMe reduced APAP toxicity and was more potent than NAC in reducing APAP hepatotoxicity.     

A patient-tailored N-acetylcysteine protocol for acute acetaminophen intoxication

BACKGROUND: Hepatotoxicity as a result of acetaminophen(APAP) intoxication has become an important problem, but early intervention with N-acetylcysteine (NAC) is effective in preventing hepatic injury. Two NAC regimens are currently approved for acute APAP intoxication: NAC administered orally every 4 hours for 72 hours, and NAC administered intravenously for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. However, clinical observations suggest that a variable treatment duration may be more appropriate than use of these predetermined, fixed-duration protocols. OBJECTIVES: This study investigated the tolerability and efficacy of a patient-tailored NAC protocol for acute APAP intoxication by comparing the incidence of hepatotoxicity in patients receiving this protocol and in historical controls receiving 1 of 2 fixed-duration protocols: oral NAC for 72 hours and intravenous NAC for 20 hours within 8 to 10 hours after ingestion of a potentially hepatotoxic amount of APAP. METHODS: This was a retrospective case series study that included all patients admitted through the emergency department (ED) of the National Taiwan University Hospital with a diagnosis of APAP intoxication between October 1997 and October 2002. According to the patient-tailored protocol, which had been used in the ED since 1997, patients with a serum APAP concentration above the limit for possible risk based on a modified Rumack-Matthew nomogram received oral treatment with NAC 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours. NAC treatment was discontinued when the APAP concentration was <10 mg/L and serum aspartate aminotransferase (AST) was <40 IU/L. For the purposes of assessing clinical outcomes, patients were divided into 3 groups based on duration of treatment: the short-course group (/=73 hours). The primary outcome measure was development of hepatotoxicity, defined as a serum AST or alanine aminotransferase concentration >1000 IU/L. RESULTS: Twenty-seven patients were included in the study, 17 in the short-course group, 4 in the intermediate-course group, and 6 in the long-course group. The mean (SD) durations of NAC treatment in the respective groups were 22.1 (5.5) hours, 45.0 (8.2) hours, and 97.3 (33.2) hours. All 6 patients (22%) in the long-course group had hepatotoxicity (peak AST range, 1083-9770 IU/L); their treatment duration ranged from 80 to 164 hours. No patients in the short- or intermediate-course group had evidence of hepatotoxicity. One woman in the long-course group in whom initiation of NAC treatment was delayed by 28 hours died of fulminant hepatic failure. The overall incidence of hepatotoxicity was similar to that in the historical controls. CONCLUSIONS: In this retrospective case series inpatients who received patient-tailored NAC therapy for acute APAP intoxication, the incidence of hepatotoxicity was low and comparable to that in historical controls who received treatment with 1 of 2 fixed-duration regimens. Use of this protocol may have the potential to shorten hospital stays without increasing the risk to patients. However, the sample size was small, and the findings require confirmation in prospective clinical trials.     

慢性丙型肝炎肝组织学改变与肝脏瘦素表达的关系

目的研究慢性丙型肝炎(CHC)肝组织学改变与肝脏瘦素表达的关系。方法未经治疗的53例成年CHC患者分为肝脏瘦素阳性组26例和阴性组27例,以单纯非酒精性脂肪性肝病(NAFLD)15例作为对照组,比较各组肝脏瘦素阳性率、肝脏炎症分级、纤维化分期和脂肪变分级有无差异。结果 CHC组脂肪变分级程度轻于NAFLD组(χ2=13.20,P<0.05),但两组分别在脂肪变1级和2级的肝脏瘦素阳性率差异无统计学意义(χ2=2.57,0.04,P均>0.05);两组在轻度炎症和轻度纤维化的瘦素表达阳性率差异有统计学意义,CHC组肝脏瘦素阳性率低于NAFLD组(χ2=4.54,6.86,P均<0.05)。两组CHC的肝脏瘦素阳性率在不同肝脏炎症分级、纤维化分期和是否发生肝脂肪变差异无统计学意义(χ2=0.106,0.846,0.000,P均>0.05),CHC的肝脏瘦素阳性率与肝脏炎症分级、纤维化分期、脂肪变分级和血清HCVRNA水平无明显相关性(P均>0.05)。结论 CHC发生肝脂肪变、肝脏炎症和纤维化程度均与肝脏瘦素表达无明显相关。     

新辅助化疗加手术在可切除小细胞肺癌中的疗效分析

目的探讨可手术切除小细胞肺癌以外科手术为主综合治疗的意义。方法回顾性分析2000年1月至2005年1月外科治疗82例小细胞肺癌的临床与生存资料,根据综合治疗方案中手术与化疗的先后顺序将本组患者分为新辅助化疗组(NAC组)与直接手术组。结果 NAC组53例,术前经1～2周期EP方案(足叶乙甙、顺铂)新辅助化疗,有效率81.1%(43/53),3例组织学完全缓解;直接手术组29例。NAC组1、3、5年生存率分别为86.8%、49.1%、28.3%,显著高于直接手术组的79.3%、31.0%、10.3%(P均<0.05),中位生存时间分别为36个月、25个月。结论可手术切除小细胞肺癌应采取以外科手术为主的综合治疗策略,术前确诊并采用NAC能够进一步提高长期生存率。     

抑制血清TNF-α对大鼠脂肪肝的影响的实验研究

目的观察肿瘤坏死因子-α抑制剂己酮可可碱,对乙醇及高脂饮食诱导造模的大鼠脂肪肝形成的影响。方法将24只大鼠分成对照组、造模组和己酮可可碱组（PTX组）三组,造模组、PTX组采用乙醇及高脂饮食诱导进行脂肪肝造模,同时分别给予蒸馏水、己酮可可碱预防治疗12周。治疗后测定各参数及肝脏病理检查。结果PTX组大鼠血清TNF—α、ALT、AST浓度及肝脂的含量、肝病理脂肪化程度均低于造模组（P〈0．05）。结论肿瘤坏死因子-α抑制剂己酮可可碱能有效防治大鼠脂肪肝形成。     

Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats

OBJECTIVES: The aim of this study was to investigate the effects of thymosin alpha(1) (Talpha(1)) in rats having fructose-induced steatosis. Fructose leads to experimental steatosis in the liver by exerting its effect on some components of the oxidant/antioxidant system, and on several cytokines (interleukin-1beta, -2, and -6) in blood. METHODS: Twenty-four rats at random were divided into three groups (each group containing eight animals); the control group (C), which received a purified diet; the high-fructose-fed group (F); and the high-fructose-fed and Talpha(1) injected group (F + T). After the experimental period of 10 days, liver lipid peroxidation and antioxidant status, and blood IL-1beta, IL-2, and IL-6 levels were quantified. RESULTS: In comparison with the C group, the F group had a higher nitric oxide (NO) level, xanthine oxidase (XO) activity, and lipid peroxidation, as indicated by concentrations of thiobarbituric acid reactive substances (TBARS), and lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the liver. In the F + T group, these markers were near the values of the control group. In addition, increased IL-1beta and IL-6 levels were kept at near to normal levels with treatment of Talpha(1), but not IL-2 levels. In the F group, the most consistent findings in the histologic sections of liver tissues were the macrovesicular and microvesicular steatosis. Talpha(1) treatment protected the majority of the liver cells, while minimal macrovesicular and microvesicular steatosis was observed in the remaining cells. CONCLUSIONS: These results show that a high-fructose diet in rats leads to hepatic steatosis and a defect in the free radical defense system, and that treatment of Talpha(1) may improve these biochemical and morphologic changes in the fructose-fed rat livers.