病毒性肝炎性激素水平的探讨

用放射免疫法检测105例各型病毒性肝炎男性患者的血清酮(T)、雌二醇(E_2)、雌三醇(E_3),T 值和E_2值在肝炎各组与正常、存活组与死亡组,伴“女性化”体征组与无“女性化”体征组均无明显性差异(P>0.05)。提示与慢性肝病雄性激素水平降低、雌性激素水平升高的传统理论相违,性激素水平高低与预后无明显关系。

Construction of Urban Overall Water Environment in Xi'an City

[Objective] The aim was to study on construction of overall water environment in Xi＇an. [Method] The study discussed necessity and basic principles of over-all restoration and construction of ＂Chang＇an Eight Water＂ from urban planning, and explored related methods from long term planning and concrete construction approaches. [Result] The study proposed that urban landscape substrates of ＂Chang＇ an Eight Water＂ should be restored based on overall planning about urban water environment, change of linear metabolism, and construction of drainage circulation system. Furthermore, self-circulation and purification of rainfall and sewage could be made use of there in view of present urban water environment. In addition, urban ＂metabolism＂ should be restored progressively to improve urban environment with consideration of water catchment, storage, and diversion. [Conclusion] We should take the initiative to catch the special opportunity to build Xi＇an into an international metropolis with overall planning, designing and implementation, which will be conducive to reconstruction of water system and pleasant surroundings, and to presentation of urban ecosystem and context in ＂Chang＇an Eight Water＂, providing many opportunities for urban development.

Prevalence of Metabolic Syndrome and Its Associations with Other Metabolic Disorders and Cardiovascular Changes in Health Examination Population in Beijing

Objective To investigate the prevalence of metabolic syndrome(MS) and its associations with other metabolic disorders and cardiovascular changes in health examination population in Beijing.Methods Totally,10 916 individuals who received health examination in Health Examination Center of Peking Union Medical College Hospital were enrolled.The height,weight,blood pressure,serum levels of triglyceride,high-density lipoprotein cholesterol(HDL-C),and fasting blood glucose were recorded.MS was diagnosed based on the working criteria of Chinese Diabetes Society 2004(CDS2004).Meanwhile,other metabolic disorders,including fatty liver and hyperuricemia,were recorded.The cardiovascular changes were reflected by the reports of electrocardiogram(ECG) ST-T changes and atherosclerosis of retinal arteries.Results The overall prevalence rate of MS was 6.1%(666/10 916) in the population.The prevalence rate of MS in male was much higher than that in female(9.0% vs.2.7%,P=0.000).For individuals with MS,the prevalence rates of fatty liver and hyperuricemia were significantly higher than those without MS,respectively(70.4% vs.35.4%,P=0.000;29.9% vs.17.7%,P=0.000).As for cardiovascular changes,the prevalence rates of ECG ST-T changes and atherosclerosis of retinal arteries were significantly higher in individuals with MS than those without MS,respectively(13.8% vs.11.7%,P=0.012;12.0% vs.6.8%,P=0.000).Conclusions The prevalence of MS in Beijing population is high.The individuals with MS have a higher risk for other metabolic disorders and cardiovascular changes.

An innovative approach for the treatment of Alzheimer's disease: the role of peroxisome proliferator-activated receptors and their ligands in development of alternative therapeutic interventions

Alzheimer＇s disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment, q-his innovative approach will lead to the identification of new targets for the preparation of new effective drugs. Peroxisome proliferator-activated receptors and their ligands are the ideal candidates to reach the necessary breakthrough to defeat this complicate disease.

Identification of the metabolite and cytochrome P450 isoforms involved in rat liver microsomal metabolism of TM208

To identify the metabolite and CYP450 isoforms involved in rat liver microsomal metabolism of TM208. The present study investigated the metabolism of TM208 and the effects of selective CYP450 inhibitors on the metabolism of TM208 in rat liver microsomes. Various specific inhibitors of CYP were used to identify the isoforms of CYP involved in the metabolism of TM208. The inhibitor of CYP2D and that of CYP2B had strong inhibitory effects on TM208 metabolism in a concentration-de- pendant manner, the inhibitor of CYP1A had a modest inhibitory effect, and the inhibitor of CYP3A seemed not to have an obvious inhibitory effect on TM208 metabolism. TM208 might mainly be metabolized by CYP2D and CYP2B in rat liver microsomes.

Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications.METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically.RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCVassociated HCC and control groups was (6.13±3.94),(5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closelycorrelated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.

Metabolic Control and Growth Regulation in the Regenerating Human Liver Measured in Vivo by 31—phosophorus Magnetic Resonance Spectroscopy

Objectives Partial hepatectomy induces a rapid transformation within the remnant liver, prompting a wave of hepatocyte mitosis which abates when the lost cell mass has been recovered. The mechanism of co-ordinated control of metabolism and maintenance of function during this period of dynamic change is incompletely understood. Furthermore, the biochemical basis of growth regulation in the regenerating liver has not been well defined. We have studied human liver regeneration using in vivo 31-phosphorus magnetic resonance spectroscopy (31 P MRS). This non-invasive technique allows assay of high-energy phosphate compounds and also of phospholipid metabolites thought to be involved in cellular renewal processes.Methods Five patients undergoing liver resection were studied. Hepatic metabolism was evaluated using 31P MRS before surgery and on postoperative days 2,4,6 and 14. Estimation of liver volume by magnetic resonance imaging and blood sampling for biochemistry were performed at the same time points.Results We found that the regenerative response following loss of liver parenchyma produced a reversible decline in energy state which necessitated compensatory adjustments in liver synthetic and excretory (unctions. Volume regain was associated with alterations in phospholipid metabolism, which normalized when the hepatic growth spurt was completed.Conclusion These observations indicate that modulation of hepatocyte energy economy is necessary for the integrated recovery of liver cell mass and function. We propose that deficient hepatic energy production may explain the mechanism of liver failure after hepatectomy, and suggest that in vivo measurement of liver metabolism may provide a rational basis for the development and evaluation of hepatic support strategies.

Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro

AIM： To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells （MSCs） could be maintained in serum from acute-on- chronic liver failure （ACLF） patients.METHODS： Hepatocyte supportive functions and cy- totoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evalu- ated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture, respectively. Chemo- kine profile was also examined for the normal serum and liver failure serum.RESULTS： Hepatocyte growth factor （HGF） and Tumor necrosis factor; tumor necrosis factor （TNF）-a were re- markably elevated in response to ACLF while epidermal growth factor （EGF） and VEGF levels were significantly decreased. Liver failure serum samples induced a higher detachment rate, lower viability and decreased liver sup- port functions in the homo-hepatocyte culture. Hepato-cytes co-cultured with MSCs could tolerate the cytotoxic- ity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cul- tured with healthy human serum in vitro. In addition, co- cultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum.CONCLUSION： ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in Xinjiang, China

AIM: To analyze the relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 andKazakh's esophageal squamous cell cancer in China.METHODS: The genotypes of cytochromes P450 (CYP) 2E1 and glutathione S-transferase (GST) M1 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) following PCR in 104 Kazakh's patients with esophageal cancer (EC) and 104 non-cancer controls.RESULTS: The frequency of CYP2E1 c1/c1 genotype was significantly higher in patients with cancer (77.9%) thanin control subjects (24.0%) (P＜0.05; OR, 11.13; 95%CI,5.84-21.22). The difference of GSTM1 null was significantly more frequent in the cancer (34.6%) vsthe control group (3.8%) (P＜0.05; OR, 13.24; 95%CI, 4.50-38.89). On the other hand, the combination of GSTM1 presence and CYP2E1 c1/c1 genotypes increased the risk for cancer (P＜0.05;OR, 13.42; 95%CI, 6.29-28.3).CONCLUSION: The CYP2E1 c1/c1, GSTM1 deletion genotypes are genetically susceptible biomarkers for ESCC in Kazakh population. Individuals with allele c1 of RsaI polymorphic locus for CYP2E1 may increase the risk of ESCC. Moreover, CYP2E1 wild type (c1/c1) increased thesusceptibility to ESCC risk in Kazakh individuals with GSTM1 presence genotype.

Analysis of Metabolic Products by Response Surface Methodology for Production of Human-like Collagen II

Recombinant Escherichia coli BL21 is used to produce human-like collagen. The key constituents of media are optimized using response surface methodology (RSM). Before thermal induction, the highest biomass production and the lowest production of some hazardous by-products, especially acetic acid, were obtained in the media containing 0.085 mol·L-1 glucose and 0.019 mol·L-1 nitrogen (carbon-nitrogen ratio, 4.47:1). After thermal induction, when the concentrations of glucose and nitrogen in the media were 0.065 mol·L-1 and 0.017 mol·L-1 , respectively (carbon-nitrogen ratio, 3.82:1), the productivity of human-like collagen per cell was the highest while that of acetic acid was the lowest. The extended analysis showed that the production of lactic acid and propionic acid increased while that of some intermediate acids of the tricarboxylic acid cycle decreased if the dose of glucose increased.

Biotransformation of aesculin by human gut bacteria and identification of its metabolites in rat urine

AIM： To observe the biotransformation process of a Chinese compound, aesculin, by human gut bacteria, and to identify its metabolites in rat urine.METHODS： Representative human gut bacteria were collected from 20 healthy volunteers, and then utilized in vitro to biotransform aesculin under anaerobic conditions. At 0, 2, 4, 8, 12, 16, 24, 48 and 72 h postincubation, 10 mL of culture medium was collected. Metabolites of aesculin were extracted 3 × from rat urine with methanol and analyzed by HPLC. For in vivo metabolite analysis, aesculetin （100 mg/kg） was administered to rats via stomach gavage, rat urine was collected from 6 to 48 h post-administration, and metabolite analysis was performed by LC/ESI-MS and MS/MS in the positive and negative modes.RESULTS： Human gut bacteria could completely convert aesculin into aesculetin in vitro. The biotransformation process occurred from 8 to 24 h post-incubation, with its highest activity was seen from 8 to 12 h. The in vitro process was much slower than the in vivo process. In contrast to the in vitro model, six aesculetin metabolites were identified in rat urine, including 6-hydroxy-7-glucocoumarin（M1）, 6-hydroxy-7-sulf-coumarin （M2）, 6, 7-digluco-coumarin （M3）, 6-glc-7-gluco-coumarin （M4）, 6-O-methyl-7-gluco-coumarin （MS） and 6-O-methyl-7- sulf-coumarin （M6）. Of which, M2 and M6 were novel metabolites.CONCLUSION： Aesculin can be transferred into aesculetin by human gut bacteria and is further modified by the host in vivo. The diverse metabolites of aesculin may explain its pleiotropic pharmaceutical effects.

Alcohol and liver

Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage. Alcoholic liver disease （ALD） has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

Obesity, metabolic abnormalities, and mortality in older men

Background Older adults are prone to obesity and metabolic abnormalities and recommended to pursue a normal weight especially when obesity and metabolic abnormalities are co-existed. However, few studies have reported the possible differences in the effect of obesity on outcomes between older adults with metabolic abnormalities and those without metabolic abnormalities. Methods A total of 3485 older men were included from 2000 to 2014. All-cause mortality and cardiovascular mortality were obtained during a mean follow-up of five years Metabolic abnormalities were defined as having established hypertension, diabetes, or dyslipidemia and taking the disease-related medications. All participants were stratified by the presence or absence of metabolic abnormalities. Results In the non-metabolic abnormalities group, all-cause and cardiovascular deaths were lowest in overweight participants and highest in obese participants. In the metabolic abnormalities group, mortality was also lowest in overweight participants but highest in participants with normal weight. After adjustment for covariates, hazard ratios （95% CI） for all-cause death and cardiovascular death were 0.68 （0.51, 0.92） and 0.59 （0.37, 0.93）, respectively, in overweight participants with metabolic abnormalities. Furthermore, obesity was not associated with mortality risk in both groups. These findings were unchanged in stratified analyses. Conclusions Overweight was negatively associated with mortality risk in older men with metabolic abnormalities but not in those without metabolic abnormalities. Obesity did not increase death risk regardless of metabolic abnormalities. These findings suggest that the recommendation of pursuing a normal weight may be wrong in overweight/obese older men, especially for those with metabolic abnormalities.

Associations between walking parameters and subsequent sleep difficulty in older adults: A 2-year follow-up study

Purpose: This 2-year follow-up study aimed to examine the associations between total volume, frequency, duration, and speed of walking with subsequent sleep difficulty in older adults.Methods: A total of 800 older adults aged 65 years and over participated in the first survey in 2012 and 511 of them were followed 2 years later.The 5-item Athens Insomnia Scale(AIS-5) was used to measure sleep difficulty. Frequency, duration, and speed of outdoor walking were self-reported. Walking speed was assigned a metabolic equivalent value(MET) from 2.5 to 4.5. Total walking volume in MET-h/week was calculated as frequency × duration × speed. Negative binomial regressions were performed to examine the associations between volume and components of walking with subsequent sleep difficulty with covariates of age, sex, education, marital status, living arrangement, smoking, alcohol consumption, mental health, Charlson Index, exercise(excluding walking), and sleep difficulty at baseline.Results: Participants with low walking volume had a higher level of sleep difficulty 2 years later compared with those with high walking volume(incident rate ratios = 1.61, p = 0.004). When speed, frequency, and duration of walking were simultaneously entered into 1 model, only walking speed was significantly associated with subsequent sleep difficulty(after the model was adjusted for covariates and baseline sleep difficulty).Sensitivity analyses showed that walking duration emerged as a significant predictor among 3 walking parameters, with 2-year changes of sleep scores as dependent variable.Conclusion: Total amount of walking(especially faster walking and lasting for more than 20 min) is associated with less subsequent sleep difficulty after 2 years among older adults.

Effects of Gancao Nourish-Yin Decoction on Liver Metabolic Profiles in hTNF-αTransgenic Arthritic Model Mice

Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'physical status.However,its mechanism of function has not been investigated.Metabolic perturbations have been associated with RA,and targeting the metabolic profile is one of the ways to manage the disease.The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factorα(hTNF-α)transgenic arthritic model mice.Methods hTNF-αtransgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group.After 8 weeks of treatment,liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis.Significantly regulated metabolites by GNYD treatment were first identified,followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis.Results A total of 126 metabolites were detected in the liver.Compared with the control group,17 metabolites in the GNYD group were significantly altered.Specifically,thiamine,gamma-L-glutamyl-L-valine,pantothenic acid,pyridoxal(vitamin B6),succinic acid,uridine 5′-diphospho-glucuronic acid,uridine,allantoic acid,N-acetyl-D-glucosamine,nicotinamide ribotide,and N2,N2-dimethylguanosine were down-regulated by GNYD treatment,whereas isobutyrylglycine,N-acetylcadaverine,N-carbamoyl-L-aspartic acid,L-anserine,creatinine,and cis-4-hydroxy-D-proline were up-regulated.Six metabolic pathways were significantly altered including the alanine,aspartate,and glutamate metabolism;pyrimidine metabolism;thiamine metabolism;amino sugar and nucleotide sugar metabolism;pantothenate and CoA biosynthesis;and citrate cycle.Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium,respectively.Conclusions GNYD can modulate the hepatic metabolism of hTNF-αtransgenic arthritic model mice.Further optimization of this decoction may lead to better therapeutic effects on RA patients.

New Artistic-Iconological Interpretations in Ecourbarchitecture

In this paper, the author focuses on the ecourbarchitectonic physical structures created after year 2000, whose artistic-esthetic value has an iconological character. An entirely new approach in formation of the facade and roof planes as well as of the forms of structures whose appearance resemble sculptural creations has been analyzed. The buildings from all over the world, with different functions contents, indicate a tendency of a different understanding of interpretation of physical structures and correlation with natural and artifact environment. Water surfaces and vegetative material contribute to an effective, cultural, majestic impression of engineering-technological philosophy of city building. The examples in the paper suggest the obvious need of radical changing of the way of thinking in the application of the design strategy in conceptualization of urban agglomerations, and essentially important, conceptually inspired metabolic of relationships among the spatial structures. The world entered new non-globalization trends of creation of the city memory, of the new iconically, symbolically strong, non-cliché, non-standard forms which define the contemporary cultural-artistic and historical identity of macro-ambient entities. This is a good and encouraging sign.

The Trace Element Content Observed in the Elderly People of Russia＇s North Regions

To investigate the status of mineral metabolism in people residing in huge regional centers of north-western and north-eastern parts of Russia by AES-IBP （atom-emission spectrometry with inductively bonded argon plasma）, the content of 25 elements in hair samples of surveyed people was examined. The results of the study carried out in Russia＇s north could testify to significant deformation found in the elderly people bodies＇ element profiles. The pronounced deficit in such essential elements as Ca, Cr, Mg can be considered the common north-related profile typical for the elderly people from European and Asian north. In addition, age-related formation of all the elements＇ deficit due to their risen spending at pathologies as well as the increased need in such elements as Zn, Se, Cr, Cu, Mn. The age-related excess of arsenic proved to be typical for Magadan residents. In Anadyr, the age-related excess of lead was found, in Petrozavodsk mercury, and in Arkhangelsk--boron and aluminium.

EB病毒抗体联合检测在小儿感染性疾病诊断中的应用

目的探讨EB病毒抗体联合检测在小儿感染性疾病诊断中的临床应用。方法 采用化学发光法定量检测患儿血清中的EB病毒VCA-IgM、VCA-IgG、EBNA-IgG含量，阳性标本加做EBV-DNA检测。结果 326例疑似EB病毒感染患者，抗体检测阳性率为81.90%（267/326）；单个抗体VCA-IgM、VCA-IgG、EBNA-IgG阳性率分别为24.85%、77.30%、53.99%。267例抗体阳性患儿中，原发感染81例，疾病累及全身多个系统。抗体联合检测出现5种组合类型，抗体检测与EBV-DNA检测结果差异无统计学意义（P〉0.05）。结论 多种抗体联合检测可提高EB病毒检出阳性率，动态反映病毒感染水平，为临床医生对EB病毒的诊断、治疗提供依据。

乳腺血氧及三算子图像在乳腺癌诊断中的价值

目的 探讨乳腺血氧及三算子图像在乳腺癌诊断中的应用价值.方法 通过对515例乳腺肿块患者进行乳腺血氧及三算子图像、彩超及钼钯三项检查,将其检查结果与金标准进行对比,得出各种检查方法的敏感度、特异度、准确性、阳性预测值、阴性预测值,并进行比较.结果 血氧及三算子成像系统与钼钯比较敏感度差异有统计学意义（P＜0.05）,准确性、特异度、阴性预测值及阳性预测值差异无统计学意义（P＞0.05）.血氧及三算子成像系统与彩超比较敏感度、准确性、阴性预测值及阳性预测值差异有统计学意义（P＜0.05）,特异度差异无统计学意义（P＞0.05）.结论 在乳腺癌的重要检查手段钼钯与超声检查比较中,乳腺血氧成像及三算子成像检查能便捷、全面地提供乳腺肿块的功能及形态影像,可使其成为乳腺癌筛查体检中的重要检查方法.

In vitro metabolism and inhibitory effects of atractylenolideⅡon various hepatic CYPs in HLMs

In the present study,we aimed to investigate the interaction between atractylenolideⅡ(AT-Ⅱ)and CYP450 enzyme in human liver microsomes,and to lay a theoretical foundation for predicting the possible interaction of AT-Ⅱin combination with drugs.The chemical inhibition experiment was carried out with specific inhibitors to clarify the CYP450 subtypes affecting the metabolism of AT-Ⅱ,and the mechanism,kinetics,and type of inhibition of CYP450 enzyme by AT-Ⅱwere studied by using the probe-based determination method of human liver microsome system with the related data of IC50 and Ki as evaluation indexes.The metabolism of AT-Ⅱwas affected by CYP1A2,CYP2C9 and CYP3A4 inhibitors,and the highest inhibition rates were41.35%,41.97%and 82.45%,respectively.The IC50 values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 69.7,84.3,92.4,173.8 and 190.1μmol/L,respectively.The Ki values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 190.6,179.1,>200,72.2 and 66.8,respectively.Among these enzymes,AT-Ⅱexhibited non-competitive inhibition on CYP1A2,showed competitive inhibition on CYP2C9 and CYP3A4,and displayed mixed AT-Ⅱinhibition on CYP2C19 and CYP2D6.CYP1A2,CYP2C9 and CYP3A4 were involved in the AT-Ⅱmetabolism,and AT-Ⅱexhibited different inhibitory mechanisms and strengths for the five subtypes of CYP450.