The changes of metabolic profile are closely related to external stimulus, and the concentration of the metabolite can directly reflect the physiological or pathological states of organisms. Therefore, the quantitative detection of metabolites is necessary. However, traditional targeted metabolomic methods have such drawbacks as narrow coverage and low sensitivity. In recent years, derivatization techniques have developed rapidly in the field of metabolomics. Derivatization reagents for amine, hydroxyl, carboxyl, carbonyl, hydrosulphonyl and other groups have been used in metabolomics research. This paper introduces various derivatization reactions and their applications according to group classification and reviewes the characteristics of multi-group derivatization techniques, with a propect of their research directions and challenges.

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity

To investigate the regulatory effects of insulin and oleic acid on serum metabolites in colon cancer, subcutaneous transplantation tumor model of colon carcinoma cell HCT116 was established. Nude mice were randomly divided into 4 groups: control (CON, vehicle); insulin treatment (INS, sc, 2.5 U/kg); oleic acid treatment (OA, ig, 2.0 g/kg); and insulin (sc, 2.5 U/kg) plus oleic acid (ig, 2.0 g/kg) treatment (IO). Non-target metabolomic analysis on the blood samples was performed by GC/MS and LC-IT-TOF/MS. Data pre-processing, including peaking, spectral deconvolution and peak alignment, was performed before data were imported to SIMCA-P for multivariate statistical analysis. Results showed that body weight of individuals in IO group was the lowest, but the tumor weight was the heaviest. Metabolic profiles of IO group were also different compared with the CON group, and the contributing metabolites were urea, arabinose, cholesterol, L-acetylcarnitine and sphingosine. There was no significant difference between OA or INS and CON. This study showed that the combination of insulin and oleic acid promoted colon cancer deterioration and caused metabolic disturbance in blood.Our study may provide theoretical foundation for the discovery of colon cancer biomarker and its early diagnosis.

Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine.

Purpose To investigate the value of T2WI mild-moderate signal and restricted diffusion in the context of liver imaging reporting and data system (LI-RADS) (2014 edition) in the diagnosis of hepatocellular carcinoma (HCC) with cirrhosis caused by hepatitis B virus.Materials and Methods A total of 77 lesions (LI-RADS 3-5,size of 1.1 cm×0.7 cm-12.7 cm×9.1 cm) of 69 HCC patients in Beijing Friendship Hospital from January 2012 to November 2016 were retrospectively analyzed.All these patients underwent MRI scan and multiphase dynamic enhanced scan.The images were analyzed by two radiologists.If a disagreement occurred,liver accelerated volume acquisition and multiphase dynamic enhanced scan were combined to reach a consensus.The contrast noise ratio (CNR) and apparent diffusion coefficient (ADC) of T2WI and diffusion weighted imaging (DWI) sequences were compared,as well as the identification of the two signs.Results There was no statistically significant difference between T2WI mild-moderate signal and restricted diffusion in the identification of lesions (LI-RADS 3-5) (P＞0.05),while the sensitivity with DWI b=0 (61.0％) was significantly lower than DWI b=600 s/mm2 (70.1％) (P＜0.05).The CNR of all DWI sequences (b=0,600 s/mm2) were larger than those of T2WI (P＜0.01).The ADC of small lesions (diameter ＜2 cm) were larger than those of larger lesions (diameter ＞2 cm) [(1.57+0.37)×10-3 mm2/s vs.(1.37+0.51)×10 3 mm2/s,P＜0.05].Conclusion There is no significant difference in sensitivity of lesions between T2WI mild-moderate signal and restricted diffusion.However,due to different CNRs,DWI with b=600 s/mm2 is more obvious for the lesions,and can be first investigated in practice.

Huangqin Decoction is a classic recipe for treatment of diarrhea from Treatise on Exogenous Febrile Disease,and consists of Scutellaria baicalensis,Paeonia lactiflora,Glycyrrhiza uralensis and Ziziphus jujuba.Huangqin Decoction has been used for nearly 1800 years for the treatment of gastrointestinal ailments,including dysentery,diarrhea and so on.Treatment of gastrointestinal disease by traditional Chinese medicine is considered to be safer than western medicine.This paper presented a review ofpharmacodynamic material basis of Huangqin Decoction,its advances in treating ulcerative colitis and reduction of the gastrointestinal side effects arising from chemotherapy drugs according to related literature.It also reviewed the deficiencies in present research,outlined the future direction and provided reference for further study.

Objective Toinvestigatetherelationbetweenserumneuron-specificenolase(NSE), bilirubinandcerebraldysfunction,prognosisafterlarge-arteryatheroscleroticstroke.Methods According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST)criteria,all the 73 patients with large artery atherosclerotic stroke were divided into the test group (41 cases ) and control group (32 cases ) according to the elevated or normal levels of serum NSE and total bilirubin. At the first day of their hospitalization,the National Institutes of Health Stroke Scale (NIHSS)score was conducted,their serum NSE,bilirubin (total bilirubin,direct bilirubin,indirect bilirubin)levels were detected,and were compared with the reevaluation of 7 and 14 days of their hospitalization and reexamination results. The modified Rankin Scale (mRS)was use to assess the recovery of their neurological function at day 30 after onset/admission. The prognosis of the patients was followed up at 1 year after onset/admission. The Kaplan-Meier product-limit method was used to conduct the analysis of the good outcome rate,and the good outcomes of both groups/interlayers (different bilirubin and NSE levels)were tested with Log-rank test. Results (1)The NIHSS scores,the levels of serum bilirubin and NSE at day 1,7,and 14 in the test group were significantly higher than those of a control group (all P<0. 01). The levels of serum bilirubin and NSE at day 7 and 14 were lower than those at day 1. (2)The mRS score at day 30 between the test group and the control group was singnificantly different (Z =3. 286,P =0. 001). (3)At day 1,the CT detection rate of large area cerebral infarction of the test group was significantly higher than that of the control group (56. 1%[n=23]vs. 28. 1%[n=9]). There was significant difference (χ2 =5. 712,P=0. 017). (4)The analysis result of Kaplan-Meier showed that there was no significant difference in its good outcome no matter grouped by the test or by serum NSE level stratification of the patients on admission (the accurateχ2valueswere4.063and4.685respectively,P=0.044and0.030respectively).Conclusion Early high-level serum NSE and hyperbilirubinemia can be used as the indexes of early identification of poor prognosis in patients with large-artery atherosclerotic stroke.

Objective To evaluate biocompatibility of Allomax mesh implanted in different planes of abdominal wall in a rats model.Methods SD rats were randomly assigned to the profacial group (Onlay group),the retro-rectus group (Sublay group) versus the intraperitoneal group(IPOM group) according to different abdominal wall planes the mesh implanted,Adhesion and shrinkage of the mesh were observed,and quantitative measurements were conducted in fibroblast ingrowth,scaffold degradation,extracellular matrix deposition and numbers of vascular ingrowth after 1,3 and 6 months mesh was implanted.Results Macroscopic observation showed both Onlay and Sublay groups was superior to IPOM group in abdominal wall integration,which included shrinkage,relocation and adhesion of the mesh at all the time points,and most or whole of the mesh had incorporated with host abdominal wall at 6 months.Most of the mesh had not incorporated with host abdominal wall and shrinkage and relocation of the mesh were found in IPOM group at 6 months.Microscopic investigation showed lipocytes appeared in the mesh in Sublay group at 3 months,and numbers of ingrowth of fibroblast and neovascularization in Sublay group were significantly less than in Onlay and IPOM group at 6 months.Scaffold degradation and extracellular matrix deposition were remarkably less in Sublay group in comparison with Onlay group and IPOM group after 1,3 and 6 months.Conclusions Biocompatibility of AlloMax mesh implanted in profacial plane of abdominal wall was superior to implanted in retro-rectus plane and intraperitoneal plane as showed in a rat model.

Objective To screen strains of minipigs sensitive to highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) for evaluation of HP-PRRS live vaccine.Methods Lantang pigs, Juema, Bama and Wuzhishan ( white) minipigs were inoculated with virulent strain NVDC-JXA1 of PRRSV, and local binary hybrid pigs were used as control.The animals were continuously observed for 5 weeks on mental status, appetite, survival, etc.after inoculation of virus.The dead pigs were autopsied and the lung tissue samples were collected for detecting virus by RT-PCR.By the end of the experiment, serum of survival animals were collected for detecting PRRSV antibody by ELISA assay.Result The animals showed depression, anorexia, and other clinical signs and death in each group after inoculation.Meanwhile, the testing results were all positive in the RT-PCR and ELISA detection.Bama and Wuzhishan ( white) minipigs were the most sensitive to virulent strain NVDC-JXA1 of PRRSV regarding mortality rate.Conclusions Bama and Wuzhishan ( white) minipigs are sensitive to HP-PRRSV, and can be used for the inspection of HP-PRRS live vaccine.

OBJECTIVETo study the application of serodiagnosis of human bocavirus (HBoV) lower respiratory tract infection in children.

METHODFrom January to April, 2013, samples including serum, sputum and bronchoalveolar lavage fluids (BALFs) were obtained from 714 children hospitalized with ALRI. Serums were tested for HBoV-specific IgG and IgM antibodies by ELISA and all kinds of samples were tested for HBoV DNA by quantitative real-time fluorescent PCR. The results of HBoV serologic tests, viral DNA in sputum and their combination were compared with those of HBoV DNA in serums and/or BALFs, which was considered as the "standard". Their consistence and differences were evaluated, and the diagnostic parameters including sensitivity, specificity, positive predictive value, negative predictive value, consistency rate, Kappa value and J value were calculated. Age distributions of the HBoV positive patients tested by the latter two methods were also compared.

RESULTThe positive rate of HBoV serology was 13.2% (94/714) . The results of HBoV serology, its DNA in sputum and their combination were all consistent with those of HBoV DNA in serums and/or BALFs (χ(2) = 91.834, 124.662, 138.643, P < 0.001 for all comparisons) . Differences were significant by McNemar test (χ(2) = 23.547, 33.440, 12.410, P all <0.001) . All the diagnostic parameters for single HBoV serologic test or single viral DNA test in sputa were approximate. However, they were improved to 70.4%, 94.8%, 38.0%, 98.6%, 93.7%, 0.463(P < 0.001), 0.65 for sensitivity, specificity, positive predictive value, negative predictive value, consistency rate, Kappa value and J value, respectively, when the methods were combined. HBoV was found positive mainly in children under 3 years of age, especially in the 1 year group. The positive rates were the highest in both group -1 year, and group -3 years was the next. However, the rate was the lowest in group >3 years and in the group -6 months.

CONCLUSIONDiagnostic power can be improved and age distribution can be demonstrated when serologic tests were combined with traditional sputum DNA detection in children with HBoV lower respiratory tract infection.

Acute Disease ; Adolescent ; Age Distribution ; Antibodies, Viral ; analysis ; blood ; Antigens, Viral ; analysis ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Human bocavirus ; genetics ; isolation & purification ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Infant ; Male ; Parvoviridae Infections ; diagnosis ; virology ; Real-Time Polymerase Chain Reaction ; Respiratory Tract Infections ; diagnosis ; virology ; Sensitivity and Specificity