[Research advances of metabolomics in early diagnosis of hepatocellular carcinoma].

Primary liver cancer is the second leading cause of death from malignant tumors in China, and hepatocellular carcinoma (HCC) is the main type. The disease stage at the time of HCC diagnosis largely determines the efficacy of subsequent treatment. Due to the HCC screening among high-risk population has not yet popularized, and the current diagnose method of early HCC is not satisfactory, the early HCC diagnosis rate is less than 30% in China. Metabolomics research emerging in recent years has promoted the research progress of HCC in many fields, such as elaborating the mechanism of occurrence and development, early prevention and diagnosis, exploring drug treatment targets. At the same time, a large number of serum metabolites with excellent sensitivity and specificity were discovered, which made up for the deficiency of traditional serological indicators and helped the early screening and early diagnosis of HCC. This review will summarize the studies on serum metabolomic markers of HCC in recent 5 years, explore the role of metabolomics in the early prediction and diagnosis of HCC and its application prospect.

[Effects of exogenous high mobility group protein box 1 on angiogenesis in ischemic zone of early scald wounds of rats].

Objective: To observe effects of exogenous high mobility group protein box 1 (HMGB1) on angiogenesis in ischemic zone of early scald wounds of rats. Methods: Thirty-six Sprague-Dawley rats were divided into HMGB1 group and simple scald (SS) group according to the random number table, with 18 rats in each group. Comb-like copper mould was placed on the back of rats for 20 s after being immersed in 100 ℃ hot water for 3 to 5 min to make three ischemic zones of wound. Immediately after scald, rats in HMGB1 group were subcutaneously injected with 0.4 µg HMGB1 and 0.1 mL phosphate buffer solution (PBS), and rats in SS group were subcutaneously injected with 0.1 mL PBS from boarders of ischemic zone of scald wound. At post scald hour (PSH) 24, 48, and 72, 6 rats in each group were collected. Protein expressions of vascular endothelial growth factor (VEGF) in ischemic zone of wound at PSH 24, 48, and 72 and protein expressions of CD31 in ischemic zone of wound at PSH 48 and 72 were detected by immunohistochemistry. The number of microvessel in CD31 immunohistochemical sections of ischemic zone of wound at PSH 48 and 72 was calculated after observing by the microscope. The mRNA expressions of VEGF and CD31 in ischemic zone of wound were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction at PSH 24, 48, and 72. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) At PSH 24, 48, and 72, protein expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group (t=7.496, 4.437, 5.402, P<0.05 or P<0.01). At PSH 48 and 72, protein expressions of CD31 in ischemic zone of wound of rats in HMGB1 group were 0.038 8±0.007 9 and 0.057 7±0.001 2 respectively, significantly higher than 0.013 4±0.004 9 and 0.030 3±0.004 0 of rats in SS group (t=10.257, 15.055, P<0.01). (2) At PSH 48 and 72, the number of microvessel in ischemic zone of wound of rats in HMGB1 group was obviously more than that of rats in SS group (t=3.536, 4.000, P<0.05). (3) At PSH 24, 48, and 72, mRNA expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group (t=4.406, 3.821, 3.356, P<0.05). At PSH 24 and 48, mRNA expressions of CD31 in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group (t=4.113, 3.466, P<0.05). At PSH 72, mRNA expressions of CD31 in ischemic zone of wound of rats in 2 groups were close (t=0.010, P>0.05). Conclusions: Exogenous HMGB1 can promote angiogenesis in ischemic zone of early scald wounds of rats by increasing expressions of VEGF and CD31.

Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin.

The frequency of poor metabolizers of debrisoquin was low and similar in four different native Chinese nationalities. In a total sample of 695 Chinese subjects, only seven (1.01%) had a urinary ratio between debrisoquin and 4-hydroxydebrisoquin greater than 12.6, which is the antimode between poor metabolizers and extensive metabolizers in white populations. This is significantly lower than the 6.82% found in 1011 white Swedish healthy subjects (p less than 0.0001). Admixture analysis indicated the occurrence of two distributions within extensive metabolizers among both Chinese and white subjects. The mean of the distribution of metabolic ratios among Chinese extensive metabolizers was shifted toward higher values compared with Swedish extensive metabolizers (p less than 0.01). The frequency of poor metabolizers of S-mephenytoin was higher in 137 Chinese (14.6%) than in 488 Swedish (3.3%) subjects (p less than 0.0001). Our findings imply that drugs metabolized by these two polymorphic hydroxylases should be prescribed in different dosages to Chinese and white subjects.

[Study on the frequency distribution of debrisoquine hydroxylation deficiency in Chinese healthy Zang and Wei volunteers].

The metabolic ratio of debrisoquine hydroxylation (MR) determined as the ratio of debrisoquine over 4-OH-debrisoquine in 8 h urine after a single oral dose of DB (10 mg) in unrelated Chinese Zang and Wei volunteers was studied by using gas chromatography. The MR of 132 healthy Chinese Zang subjects ranged from 0.20 to 34.32, and that of 158 healthy Chinese Wei subjects ranged from 0.13 to 29.73. Two phenotypes were apparent in the frequency distribution histograms with an antimode at log MR = 1.10 (MR = 12.6). Two subjects were therefore identified as poor metabolizers (PMs) of DB in 132 Zang volunteers (the frequency of PMs was found to be 1.52%), and only one in 158 Wei volunteers (0.63%). Neither sex nor smoking habit affected the DB hydroxylation (P greater than 0.2). The recoveries of DB and 4-OH-DB in Zang volunteers were 19.83 +/- 10.99 and 11.57 +/- 7.04%, and in Wei volunteers they were 22.74 +/- 14.41 and 17.77 +/- 10.82%, respectively.