Advances and Challenges of Exosome Metabolomics in Body Fluids

Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and metabolites,although most studies have primarily focused on proteins and RNA.Recently,exosome metabolomics has demonstrated clinical value and potential advantages in disease detection and pathophysiology,despite significant challenges,particularly in exosome isolation and metabolite detection.This review discusses the significant technical challenges in exosome isolation and metabolite detection,highlighting the advancements in these areas that support the clinical application of exosome metabolomics,and illustrates the potential of exosomal metabolites from various body fluids as biomarkers for early disease diagnosis and treatment.

顾櫰三《补五代史艺文志》小说著录失误考

顾櫰三《补五代史艺文志》著录小说63部,其中错讹有误的33部。以按语的形式对王仁裕《金华子杂编》等33部小说依次进行考辨,再以列表的形式总结其小说著录失误情况。通过考察可知,顾氏《补五代史艺文志》小说著录的错讹,主要体现为:误收、重出、作者有误、书名有误、卷数有误、人书不符、作者不实、作者残阙、著录模糊等。此外,五代著作断代,上限以后梁建立(907)为界,下限则根据作者实际情况,以其所处割据政权归宋的时间为限。

Pharmacokinetics of 20(R)-Ginsenoside Rg3 in Human Volunteers

Objective: To study the pharmacokinetics of 20(R)-Ginsenoside Rg3 in the human body. Methods: High-performance liquid chromatography-ultraviolet detection method was used in this study. Results: The pharmacokinetics of Ginsenoside Rg3 in 14 healthy volunteers were investigated. After a single oral dose of 3.2 mg.g-1 Ginsenoside Rg3 in 8 male volunteers, the plasma concentration-time course fitted in well with a two-compartment open model, with the following pharmacokinetic parameters: Tmax 0.660.10 h, Cmax 166 ngmL-1, T1/2a 0.460.12 h, T1/2b 4.91.1 h, T1/2(Ka) 0.280.04 h, AUC0-∞ 7726 ngmL-1h, respectively. No kinetic analysis was made after an oral dose of 0.8 mg.g-1 Rg3 in other 6 volunteers because of the low concentration, but there was a good correlation between Cmax and dosage of the two groups. Conclusion: The absorption of Rg3 was rapid in the human body, and its elimination was rapid too after oral administration of Ginsenoside Rg3. The pharmacokinetic results shows that it exhibited the first-order kinetic characteristics.

Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases

AIM： To investigate the association between serum insulin-like growth factor 1 （IGF-1）, osteocalcin, and parathyroid hormone （PTH） levels with the etiology and clinical condition of patients with chronic liver disease. METHODS： Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection： bilharziasis （9 patients）, hepatitis B virus （HBV, 12 patients） and hepatitis C virus （HCV, 29 patients）. The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group.HBsAg, HBcAbIgM, HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction （RT-PCR）. Antibllharzial antibodies were detected by indirect haemagglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted. RESULTS： Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin （14.7 ± 0.54 vs 3.6 ± 0.10, P 〈 0.05）, while that for PTH was positively correlated with total protein （70.1 ± 2.17 vs 6.7 ± 0.10, P 〈 0.05） in patients with HCV infection.

《辽代墓志校注》商榷

《辽代墓志校注》是近年出版的优秀辽代墓志著录成果,但是其录文和注释仍存在一定瑕疵。从中选取《陈万墓志》等五方墓志中的录文与简注,探讨其中可商之处。此书存在着错字、多字、少字、漏字、未识字、注释等问题。针对上述问题,需要尽力寻求第一手资料、对录文再三斟酌、关注异体字、与具体语境相结合、增强自身的文字学与历史学素养,只有这样,才能完成高质量的成果。

C-reactive protein,procalcitonin,interleukin-6,vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer

AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.

Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease(NAFLD)remains a leading cause of chronic liver disease.In the context of NAFLD,the presence of nonalcoholic steatohepatitis (NASH)portends an adverse prognosis with greater risk of liver fibrosis and cirrhosis.Although liver biopsy is the keystone of patient management in NAFLD,it is also increasingly clear that such evaluation has its limitations.The availability of biochemical markers of NAFLD and NASH has tremendous potential to radically alter management strategies for these conditions,as well as to monitor disease activity.Our article provides an overview of biomarker discovery and selection in the setting of NAFLD and highlights future directions in the field.

From Swift to Mr. Ed： Comedic Representations of the Noble Horse in High and Low Culture

Few would deny the nobility of an animal which has played a significant role, historically, in the lives of humankind： the fabled unicorn, the Trojan Horse, and Pegasus, together with the Houyhnhnms of Jonathan Swift are testaments to the nobility of horses. In a modern context, Seabiscuit, Black Beauty, Silver, steed of the iconic Lone Ranger, and Tir na nog, from Irish folk tale history, have maintained the tradition of nobility. High comedic elements such as TV＇s Mr. Ed, Aspercel, from The Horse in the Gray Flannel Suit （1968）, Ollie, of Laurel and Hardy fame, reincarnated as a horse, and Tir na nog, hiding in an elevator to avoid being apprehended by the law, help to complete the comedic portrait of equine nobility

Clinical metabolic analysis combined with traceability of biosynthetic pathway:a new approach to quality marker of Chinese materia medica

Quality marker(Q-marker)of Chinese materia medica(CMM)plays an important role in quality control of CMM products.However,its research strategy and technique remain unclear.Based on the fact that quality standard of CMM should be associated with clinical efficacy,taking Jinqi Jiangtang tablet treating type 2 diabetes as an example,the Q-marker related to activity via the reverse analysis of drug metabolism in clinic and traceability of botanic biosynthetic pathways is discovered and validated.Therefore,we proposed a new research strategy of Q-marker of CMM with"Discovery of clinical active constituents as guidance,Reverse analysis of metabolic transformations as link,and Traceability of biosynthesis pathways as key",to improve quality control of CMM products.

The Consolidation of Youth Lifestyle in the 1960s： Swinging London Through The Drapers＇Record Magazine

This paper discusses how consumerism boosted youth lifestyle in the 1960s--mainly through modem magazines （particularly in Britain） and built a territorial symbolic identity through fashion. In the 1960s, the consolidation of youth culture becomes an international phenomenon. With the development of ready-to-wear, adolescents begin to be target as a consumer market. The music and fashion industries unite to create and advertise youth lifestyle. The fashion shifts from Paris to London. Magazine articles and publicity set the latest trends. The method applied is research in primary source--the British journal The Drapers＇ Record aiming to recognize fashion transformation and juvenilization in this period of time. The magazine shows ads and fashion editorials （mainly feminine）, articles and news about fashion trend. There is also a brands guide for shoppers and retailers. The magazines used in the research are from 1964 to 1967, July and August issues, when the fall-winter trends are shown. From 1964 on, we notice the orientation towards a juvenile market and style, but these trends will only fully materialize through 1967. It leads to the conclusion that between 1965 and 1967 fashion juvenilization developed, reached its peak and global range.

Proteome Profiles of Longissimus and Biceps Femoris Porcine Muscles Related to Exercise and Resting

Exercise affects muscle metabolism and composition in the untrained muscles. The proteome of muscle tissue will be affected by exercise and resting. This is of economic importance for pork quality where transportation relates to exercise of untrained muscles. Rest reverses exercise effects. The objective of this research was to develop potential protein biomarkers that predict the optimal resting time after exercise related to optimal pork quality. Ten litters of four female pigs were within litter allocated to the four treatment groups： exercise by running on a treadmill for 27 minutes followed by rest for 0, 1, or 3 h; control pigs without exercise. Proteome profiles and biochemical traits measuring energy metabolism and meat quality traits expected to be related to exercise were determined in the Longissimus and the Biceps femoris of the pigs. The results indicated associations between protein abundances in muscles and exercise, resting, and biochemical traits.

Effect of CYP3A4*18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui subjects

In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. A pharmacokinetic study was then carried out in three groups with CYP3A4＊1/＊1 （n = 6）, CYP3A4＊1/＊18 （n = 6） and CYP3A4＊18/＊18 （n = 6） genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups （P〈0.05）. Compared with the CYP3A4＊1/＊1 group, the Cm,x of zolpidem in ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.89 （0.65-1.12） and 0.57 （0.47-0.66）, respectively, and the AUC0-1 in the ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.74 （0.22-1.26） and 0.61 （0.24-0.98）, respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A＊ 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4＊ 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.

The U-Pb chronologic evidence and sedimentary responses of Silurian tectonic activities at northeastern margin of Tarim Basin

U-Pb ages of Devonian detrital zircons from Tabei Uplift have been determined through LA-ICP-MS test technology.The results revealed that most zircon ages concentrate on 460-414 Ma,especially around 436-423 Ma,indicating possible occurrences of strong tectonic events at the northern margin of Tarim Basin during that period.Combined with previous researches on the basin marginal orogenic belts,intense tectonic activities developed at the northeast margin of Tarim Basin and its obvious sedimentary responses in basin during the end of Ordovician to Early-Middle Silurian are discussed.These include(1) several unconformities within the Late Ordovician-Silurian,showing truncation,erosion,and onlap characteristics,which reflected the local uplift formed during the surrounding extrusion process;(2) the Silurian fluvial delta system from northeast to southwest in Keping,Yingmaili,Hade,and Caohu areas,which reflected the partial uplift at the northeast margin and provided clastic supply to basin;and(3) as indicated by heavy mineral analysis,the Silurian sediments came mainly from the recycles of orogenic belts provenance,which indicated the compress tectonic setting.In addition,a wide range of red mudstone layer distribution in the upper part of the Silurian may be closely related to the surrounding tectonic uplift and the rapid decline of sea levels.

Tracking shallow marine red beds through geological time as exemplified by the lower Telychian (Silurian) in the Upper Yangtze Region,South China

Marine red beds occur frequently in China through geological time.Despite their complex environments,the red beds are found in three depositional settings:1) oceanic,deep water,as in the Upper Cretaceous of southern Tibet;2) outer shelf,deeper water,as in the Lower-Middle Ordovician of South China;and 3) inner shelf,shallow water,as in the Silurian and Triassic in South China.The Silurian marine red beds are recurrent in the lower Telychian,upper Telychian,and upper Ludlow.This paper is to document the marine nature of the lower Telychian red beds (LRBs) in the Upper Yangtze Region and to discuss the spatial and temporal distribution of the LRBs and their depositional environments.The LRBs are best developed on the north side of the Cathaysian Oldland,which can be interpreted as the source area.It is inferred that they were deposited during a marine regression,characterized by the lack of upwelling,low nutrition and organic productivity with a decrease of biodiversity and a high rate of sedimentation.The iron-rich sediments may have been transported by rivers on the oldland into the Upper Yangtze Sea,as rates of deposition were rapid enough to counteract normal reducing effect around sediment-water interface.The LRBs are different from the off-shore,deeper water red beds of lower Telychian in Avalonia and Baltica and further from the oceanic,deep water red beds of Upper Cretaceous in southern Tibet chiefly in palaeogeographic settings,biotic assemblages and marine environments.

Plasma metabolic biomarkers for syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis

OBJECTIVE： To explore the plasma metabolite pro- files in patients with the syndrome of phlegm and blood stasis in hyperlipidemia and atherosclerosis （As）, and to search for the metabolic biomarkers of the syndrome. METHODS： The plasma metabolite profiles of 31 patients with the syndrome of phlegm and blood stasis in hyperlipidemia and As, 6 patients with syn- dromes without phlegm and blood stasis, and 10 healthy subjects were analyzed by gas chromatog- raphy-mass spectrometry （GC-MS）. Partial least squares-discriminant analyses （PLS-DA） were used to carry out the pattern-recognition analyses of the data. The plasma metabolic biomarkers of patients were obtained by variable importance plot value （VlP value） and Student＇s t-test. The structures ofbiomarkers were defined by the National Institute of Standards and Technology （NIST） database. RESULTS： PLS-DA score plots of plasma metabo- Iomes did not show overlap between the phlegm-blood stasis syndrome group and syn- dromes without phlegm and blood stasis group, whereas significant differences in the concentra- tions in the plasma of 5 metabolites were found （P〈 0.05）. They were identified as urine, isoleucine, gluc- uronic acid, palmitic acid and glycerol by searching in NIST database. The concentrations of four metab- olites in the plasma of patients with syndrome of phlegm and blood stasis were higher than those with syndromes without phlegm and blood stasis, whereas the glycerol concentration was lower. CONCLUSION： Compared with patients with syn- dromes without phlegm and blood stasis, five me- tabolites showed abnormal levels in patients with the syndrome of phlegm and blood stasis. These metabolites could be diagnostic and prognostic biomarkers.

Investigating the effects of moxibustion on serum metabolism in healthy human body based on the ~1 H NMR metabolomics technology

Objective： To investigate the effects of moxibustion on the serum metabolism in healthy human body based on the 1H nuclear magnetic resonance （1H NMR） metabolomics technology, and to find the differences in metabolites, as well as to elucidate the effects of moxibustion on healthy human body from the viewpoint of global metabolism. Methods： Sixty subjects of healthy young men from the enrolled students were randomly divided into a moxibustion group and a control group using random number table, with 30 cases in each group. Subjects in the moxibustion group accepted mild moxibustion on the right Zusanli （ST 36）, once a day, 15 min for each time, and continuous treatment for 10 d; those in the control group did not receive any intervention. There were 28 cases in the moxibustion group and 23 cases in the control group after interventions. On the 2st day, 5th day and lOth day of the intervention, serum samples were collected from subjects of the two groups, and metabolic spectra were obtained by the 1H NMR technology. Results： Before and after the intervention, serum 1H NMR of the moxibustion group was significantly different, while the difference was insignificant in the control group. Metabolite changes in the moxibustion group were mainly in low density lipoprotein （LDL）/very low density lipoprotein （VLDL）, valine, isoleucine, leucine, lactic acid, glutamine, citric acid, polyunsaturated fatty acids, creatine, glycine, glycerol, glucose, tyrosine, histidine, formic acid, alanine, lysine, acetic acid, and glutamic acid. Conclusion： Moxibustion can cause changes of serum metabolic patterns in healthy human by influencing the concentrations of branched-chain amino acids, polyunsaturated fatty acids, and other metabolites to strengthen body＇s metabolisms of amino acids and fatty acid.

Effect of Qingxue Dan on obesity and metabolic biomarker: a double-blind randomized-controlled pilot study

OBJECTIVE: To investigate the clinical effect of Qingxue Dan(QXD) on obesity and metabolic biomarker related to obesity.METHODS: A randomized, double blinded, placebo-controlled trial with a paralleled study design was conducted. Twenty-six obese volunteers aged between 30 and 60 with obesity and more than 2 metabolic risk factors were recruited at the department of oriental rehabilitation medicine, Kyunghee university oriental medical hospital, Seoul, Korea. Subjects were randomly assigned to an intervention(QXD) group or a placebo group, and treated with 900 mg/d of QXD or placebo medicine for 8 weeks. Primary endpoint was the change of body mass index(BMI) at 8 week from baseline. Secondary outcomes included the change of body composition, abdominal fat mass measured with Dual energy X-ray absorptiometry(DXA), blood pressure,lipid profiles and the homeostasis model assessment for insulin resistance(HOMA-IR).RESULTS: BMI was decreased in the QXD group sig-nificantly. Total body fat, abdominal fat mass measured with DXA Region of Interest and waist circumference(WC) showed a trend toward decreasing in the QXD group, but fat free mass was decreased in all groups. Triglyceride(TG) was decreased in QXD group significantly, but WC, total cholesterol and high-density lipoprotein cholesterol were increased in both group. BP didn't change during the study period. HOMA-IR is decreased in both groups without group effect.CONCLUSION: 8-weeks of oral administrations of QXD(900 mg/d) reduces BMI, with a tendency of lose of total body fat mass, especially abdominal fat. It also significantly reduced serum TG level.These results suggest QXD could be used to treat obesity and metabolic risk factors. Further study is needed to confirm our pilot findings.

Automorphisms of the Toeplitz algebra with piecewise continuous symbol

The automorphism group of the Toeplitz algebra generated by the Toeplitz operators, whose symbols are continuous functions on the circle beside finitely fixed points, is characterized.

Effect of Huanglianjiedu Tang on fever in rats induced by 2, 4-dinitrophenol

OBJECTIVE: To study metabolic characteristics of fever in rats induced by 2, 4-dinitrophenol (DNP) and the effect of Huanglianjiedu Tang (HLJDT) on the fever. METHODS: The urine samples were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) at the positive ion mode scanning, and experimental data were analyzed by the principal component analysis. RESULTS: Eight potential biomarkers indicating the occurrence and evolvement of fever were determined according to ions in urine samples. Five of them were found increased, while the other three decreased. After HLJDD intervention, the increased five were reduced significantly in high dose group, compared with model group, while the decreased three had no obvious change. Five of the eight biomakers were identified with formyl-5-hy-droxykynurenamine, gentisic acid, aminoadipic acid, phenylacetic acid, L-phenylalanyl-L-hydroxyproline on the basis of MS/MS.These biomarkers are associated with the metabolism of 5-hydroxytryptamine, tyrosine, lysine, phenylalanine and collagen protein, respectively. CONCLUSION: HLJDT had significant effect on DNP-induced fever in rats. The effect was performed possibly by acting on 5-hydroxytryptamine in hypothalamus and some amino acid metabolism. These results suggested that HLJDT relieved fever by acting on multi-targets.