The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.
Biomarkers ; blood ; urine ; Chemical and Drug Induced Liver Injury ; diagnosis ; Humans ; Sensitivity and Specificity

Objective To investigate the association of two single nuclear peptides(SNPs)polymorphisms(rs11209026 and rs11805303)which lies in interleukin-23 receptor(IL23R)gene with susceptibility to inflammatory bowel disease(IBD).Methods The target SNPs were directly sequenced by polymerase chain reaction(PCR)and gene polymorphisms of 50 healthy and 81 patients with IBD (Crohn's disease in 41 patients and ulcerative colitis in 40 patients)were analyzed using chromassoftware.Results The geno-type frequency and allelic frequency of rs11209026 were 7.3%and 3.7%in patients with Crohn's disease respectively,15.0%and 7.5%in patients with ulcerative colitis respectively as well as 14.0%and 7.0%in normal population respectively(all P value＞0.05).The geno-type frequency and allelic frequency of rs11805303 were 22.0%and 52.4%in patients with Crohn's disease respectively,15.0% and 41.2% in patients with ulcerative colitis respectively as well as 34.0%and 59.0%in normal population respectively(all P value＞0.05).But in allelic frequency there was significant difference between ulcerative colitis patients and normal population(P=0.018).The polymorphisms of rs11805303 loci did not correlate with age,gender,disease duration.activity and site in patients with ulcerative colitis.Conclusions IL23R gene polymorphism is not associated with the susceptibility to Crohn's disease.rs11805303 allele may be related with susceptibility to ulcerative colitis.But no correlation was found between the SNP polymorphisms and the clinical characteristic of ulcerative colitis.

To explore the antibacterial activity and mechanism of total alkaloids and berberine from Coptidis Rhizoma on Aeromonas hydrophila, and determine the effect of total alkaloids and berberine from Coptidis Rhizoma on minimum inhibitory concentrations, permeability and fluidity of cell membrane, conformation of membrane proteins and virulence factors of A. hydrophila. The results showed that both total alkaloids and berberine from Coptidis Rhizoma had antibacterial activities on A. hydrophila, with minimum inhibitory concentrations of 62.5 and 125 mg · L(-1), respectively. Total alkaloids and berberine from Coptidis Rhizoma could increase the fluidity of membrane, change the conformation of membrane porteins and increase the permeability of bacteria membrane by 24.52% and 19.66%, respectively. Besides, total alkaloids and berberine from Coptidis Rhizoma significantly decreased the hemolysis of exotoxin and the mRNA expressions of aerA and hlyA (P < 0.05, P < 0.01), the secretion of endotoxin and the mRNA expression of LpxC (P < 0.05, P < 0.01). The results suggested that the antibacterial activity of total alkaloids and berberine from Coptidis Rhizoma on A. hydrophila may be related to the bacteria membrane injury. They inhibited the bacterial growth by increasing membrane lipid fluidity and changing conformation of membrane proteins, and reduced the secretion of virulence factors of A. hydrophila to weaken the pathogenicity.
Aeromonas hydrophila ; drug effects ; genetics ; metabolism ; Alkaloids ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Bacterial Toxins ; biosynthesis ; Berberine ; pharmacology ; Cell Membrane ; drug effects ; genetics ; metabolism ; Coptis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Membrane Fluidity ; drug effects ; Rhizome ; chemistry

Objective To study the mechanism of marcosomia by investigating insulin-like growth factor 2(IGF_2)imprinting status,expression level and the promoter usage in the placenta of macrosomia. Methods We selected heterozygous cases for Apa Ⅰ polymorphism in exon 9 of IGF_2 gene and then analyzed its imprinting status in 168 placentas of macrosomia and normal pregnancies.IGF_2 transcription levels and promoter usages in macrosomic and normal placenta were evaluated by using semi-quantitative RT- PCR assay.Results Thirty specimens of macrosomic placenta and 30 of normal placenta were identified as heterozygous for IGF_2.All of the heterozygous specimens showed maintenance of imprinting.The expression of placental IGF_2 mRNA(2.2?1.2)was significantly higher in macrosomia than that of normal weight group (1.6?0.6,P 0.05).Conclusion It is possible that over expression of IGF_2 in placenta contributes to macrosomia while the promoter usage and imprinting status are not associated with macrosomia.

Abstract: Objective　To investigate the molecular characteristic and evolutionary trends of full-genome sequences of coxsackievirus A2 (CV-A2) and A5 (CV-A5) in Changsha City. Methods　The CV-A2 and CV-A5 strains were isolated and detected from patients with hand, foot and mouth disease (HFMD) cases. The full-genome sequences of CV-A2 and CV-A5 strains were obtained using NGS sequencing. Homology and phylogenetic tree analysis were performed, and the recombination regions of the strains were examined by SimPlot software. Results　The full-genome sequences of CV-A2 and CV-A5 strains were obtained from routine surveillance cases of HFMD in Changsha in 2019. The CV-A2 strain was named S281/Changsha/CHN/2019 with the full-genome sequence of 7 422 bp long; the CV-A5 strain was named S272/Changsha/CHN/2019 with the full-genome sequence of 7 425 bp long. Homology analysis of the isolates by comparison with the nucleic acid sequences of CV-A2 and other CV-A2 strains in China showed that the non-structural protein region shared lower similarity than that of structural protein region. The CV-A2 showed 79.20% similarity with Fleetwood strain (NC038306), showed the highest similarity 95.60% with MN419014 strain from Hubei Province. The non-structural protein 3C and 3D region shared the lowest similarity with MN419014, 90.51 and 92.06%, respectively. Phylogenetic tree analysis showed that 3C and 3D regions were located in the CV-A4 branch. Amino acid mutation sites were found in non-structural protein region, and the amino acid sequence in structural protein region was conserved. SimPlot analysis showed that genetic recombination was found in the 3C and 3D region of CV-A2 strains. The full-genome sequence of CV-A5 showed 80.7% similarity with the Swartz (AY421763) and 97.43% similarity with the strain (MH111030) from Australian. Homology analysis showed that the non-structural protein region shared lower similarity than that of structural protein region, based on full-genome of CV-A5. Phylogenetic tree analysis showed that CV-A5 and MH111030 were in the same branch, indicating that CV-A5 strain not from local. The amino acid sequence of CV-A5 strain was conserved. Conclusions　The CV-A2 strain in Changsha City shared genome sequence information with CV-A4, and the CV-A5 strain was imported from abroad. Our findings are expected to understand the molecular and recombination characteristics of CV-A2 and CV-A5, provided the data of evolution and genetic features of the coxsackievirus, and interrupt disease transmission in a timely and effective manner.

OBJECTIVETo study the plasma protein binding rate of methyl protodioscin.

METHODThe ultrafiltration was employed to determine the plasma protein binding rate of methyl protodioscin. The plasma concentrations of methyl protodioscin were measured by HPLC-MS-MS.

RESULTThe plasma protein binding rate of methyl protodioscin with rat plasma at the concentration of 20.0, 100 and 200 microg x mL(-1) were (94.6 +/- 0.16)%, (91.6 +/- 0.35)% and (86.10 +/- 0.60)%, respectively, while the plasma protein binding rate of methyl protodioscin with normal human plasma at the above concentrations were (82.11 +/- 5.12)%, (84.54 +/- 0.32)% and (88.52 +/- 1.02)%, respectively.

CONCLUSIONThe binding rate of methyl protodioscin with plasma protein is high.

Animals ; Antineoplastic Agents ; metabolism ; Blood Proteins ; metabolism ; Calibration ; Chromatography, High Pressure Liquid ; Diosgenin ; analogs & derivatives ; metabolism ; Female ; Humans ; Male ; Protein Binding ; Rats ; Saponins ; metabolism ; Sensitivity and Specificity ; Tandem Mass Spectrometry ; Ultrafiltration

We have recentely built a cluster and backup system based on a SAN + NAS integrated storage system at a low price. The integration of SAN + NAS provides a storage system of fine quality, high reliability and high stability for hospitals. The article mainly introduces the choice of the project, the design of SAN + NAS integration and its implementation.
Computer Storage Devices ; Hospital Information Systems ; Humans ; Information Storage and Retrieval ; methods ; Internet ; Local Area Networks ; Medical Records Systems, Computerized ; instrumentation ; Software

AIMTo investigate the stepwise development and germ cell gene expression in allografted neonatal mouse testes and the differentiation of immature human testicular cells in xenografted human testes.

METHODSImmunodeficient nude mice were used as hosts for allografting of neonatal mouse testes and xenografting of human fetal testicular tissues. Stepwise development and stage-specific gene expression of germ cells in allografts were systematically evaluated and parallel compared with those in intact mice by periodically monitoring the graft status with measurement of graft weight, histological analysis and determination of five stage-specific genes. Human testicular tissues from 20 and 26 weeks fetuses were used for the xenografting study. Histological analysis of xenografts was performed 116 and 135 d after the grafting procedure.

RESULTSIn the allografting study, progressive increase in tissue volume and weight as well as in tubule diameter in grafts was observed; the appearance time of various germ cells in seminiferous tubules, including spermatogonia, spermatocytes, round and elongate spermatids and sperm, was comparable with that in intact donors; the initiation of gene transcription in grafts showed a similar trend as in normal mice. Graft weight ceased to increase after 7-8 weeks and degradation of grafts was observed after 5 weeks with progressive damage to seminiferous epithelium. In the xenografting study using immature human testicular tissues, graft survival and development was indicated by increasing graft weight, Sertoli cells differentiation into advanced stage, germ cells migration and location to the basal lamina and formation of a niche-like structure.

CONCLUSIONThe developmental course and gene expression pattern of germ cells in allografts were similar to those in intact mice. The best time point for retrieval of mouse sperm from grafts was 5-7 weeks after grafting procedure. An accelerated development of immature human testicular cells could be achieved by ectopic xenografting of human testes.

Animals ; Animals, Newborn ; Base Sequence ; DNA Primers ; Gene Expression Profiling ; Humans ; Immunologic Deficiency Syndromes ; physiopathology ; Male ; Mice ; Mice, Inbred BALB C ; Testis ; growth & development ; metabolism

OBJECTIVETo study the polysaccharide of Condonopsis pilosula.

METHODThe polysaccharide, CPP-1, was purified by DE-52 cellulose and Sephadex G-200 gel column chromatography. Purity and molecular weight of the polysaccharide were determined by gel permeation chromatography. Methylation analysis, periodate oxidation and degradation, IR, 1H-NMR and 13C-NMR methods were adopted to elucidate the chemical structure.

RESULTThe molecular weight of CPP-1 was estimated to be 7.5 x 10(4), and the structure of CPP-1 was a beta-(2 --> 1) linked beta-D-fructosan.

CONCLUSIONCPP-1 was a neutral homosaccharide.

Codonopsis ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Fructans ; chemistry