OBJECTIVE To investigate the impact of mercuric sulfide nanoparticles(HgS-NP)on various neurotransmitter-type neurons in Caenorhabditis elegans(C.elegans).METHODS Wild-type N2 C.elegans,as well as the transgenic C.elegans expressing green fluorescent protein specifically in gamma-amino-butyric acid(GABA)-ergic,glutamatergic,dopaminergic,cholinergic,and serotoninergic neurons(strains EG1285,DA1240,BZ555,LX929,and GR1366),were synchronized at the L4 stage and treated with different concentrations of HgS-NP via solid exposure.① Five transgenic strains of C.elegans were exposed to HgS-NP 0(control group),250,500,and 1000 mg·L-1 for 72 h.Fluorescence microscopy was used to observe the expression of green fluorescence in different neurotransmitter-type neurons of the corresponding transgenic C.elegans.② Wild-type N2 C.elegans were exposed to HgS-NP 0(control group)and 1000 mg·L-1 for 72 h.Real-time quantitative PCR(RT-qPCR)was performed to detect the mRNA expression levels of 33 genes related to the GABAergic and glutamatergic neurotransmitter systems.RESULTS ① Compared with the control group of the same genotype,the EG1285 C.elegans exhibited soma shrinkage,dendrite fragmentation,and neuronal loss,with a significant decrease in the relative fluorescence intensity of GABAergic neurons(P<0.05)after exposure to different concentra-tions of HgS-NP.After exposure to HgS-NP 1000 mg·L-1,the DA1240 C.elegans showed a loss of glutamatergic neurons in the head region and a significant decrease in the relative fluorescence intensity(P<0.01).However,there were no significant changes in the morphology or relative fluorescence intensity of dopaminergic,cholinergic,and serotoninergic neurons in BZ555,LX929,and GR1366 C.elegans after exposure to HgS-NP,respectively.② Compared with the control group,wild-type N2 C.elegans exposed to HgS-NP 1000 mg·L-1 showed increased mRNA expression levels of glr-7 and glr-8,which encoded non-N-methyl-D-aspartate glutamate receptors(P<0.05),while the expression levels of the remaining 31 genes related to the GABAergic and glutamatergic neurotransmitter systems showed no significant changes.CONCLUSION Exposure to a high dose of HgS-NP for 72 h may potentially damage the GABAergic and glutamatergic neurons in C.elegans,but have no significant effect on dopaminergic,cholinergic or serotoninergic neurons.

Objective To explore the mechanism of Zishen Jianpi Huayu Tablets(Corni Fructus,Notoginseng Radix et Rhizoma,Astragali Radix,Puerariae Lobatae Radix,Spatholobi Caulis,Rehmanniae Radix)in the treatment of diabetic retinopathy(DR)by means of network pharmacology and molecular docking technique,and verified by in vitro experiments.Methods The active components of Zishen Jianpi Huayu Tablets and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the BATMAN-TCM database.Drug target proteins were converted to their corresponding gene names through the UniProt database.DR-related targets were searched using"diabetic retinopathy"as a keyword in GeneCards,DrugBank,OMIM,and TTD databases.Common targets between the disease and the drug were identified using the Venny tool.These common targets were analyzed using the String database,a protein-protein interaction(PPI)network was constructed.Topological heterogeneity analysis was performed using Cytoscape 3.9.1 to select core targets and create a PPI network diagram.These common targets were entered into the Metascape database for Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis to identify potential action pathways.Molecular docking of the main active components and core targets was performed using Auto Dock tools software,followed by further experimental validation.The CCK-8 assay was used to assess the effect of Zishen Jianpi Huayu Tablet medicated serum on the cell viability of Human Retinal Microvascular Endothelial Cells(HRmECs)under high glucose conditions,and RT-qPCR was used to measure the expression of IL-1β,AKT1,VEGFA,and TP53 mRNA in HRmECs.Results(1)The effective components and corresponding target proteins of Zishen Jianpi Huayu Tablets were screened by Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and BATMAN-TCM database.The disease-related targets of DR were searched by GeneCards,OMIM and TTD databases.The use of VENNY platform for drug active components target and DR disease-related target to take intersection(common target),that is,Zishen Jianpi Huayu Tablets in the treatment of DR potential target.The network of"drugs-active components-common targets"was constructed to screen out the key active components of Zishen Jianpi Huayu Tablets in the treatment of DR.Import the common target into STRING database,obtain the PPI network relationship,and screen out the core target.Metascape platform was used to analyze the GO function and KEGG pathway enrichment of the common targets.The key active components and core targets were verified by Autodock 4 software for molecular docking.(2)The drug-containing serum and blank serum of Zishen Jianpi Huayu Tablets was prepared.Human retinal microvascular endothelial cells(HRmECs)were randomly divided into 5 groups:the control group(low-sugar DMEM medium+10%blank serum),high-glucose group(high-sugar DMEM medium+10%blank serum)and Zishen Jianpi Huayu Tablets containing low-,medium-and high-dose serum(high-sugar DMEM medium+10%low-,medium-and high-dose drug containing serum)were detected after 48 hours of culture.The proliferative activity of HRmECs cells was detected by CCK-8 method,and the mRNA expressions of IL-1β,AKT1,VEGFA and TP53 in HRmECs cells were detected by RT-qPCR method.Conclusion Zishen Jianpi Huayu Tablets may act on core targets such as IL-1β,IL-6 and VEGFA,as well as key pathways such as NF-κB signaling pathway,AGE-RAGE signaling pathway and PI3K-AKT pathway through various active components such as quercetin,kaempferol and rehmannia flavonoids,so as to play a therapeutic role in DR.

Objective Toexplorethevalueofmulti-parameterquantitativeanalysisofspectralCTimaging (GSI)indifferentiatingrenal fat-poorangiomyolipoma(fpAML)andchromophobecellrenalcarcinoma(CCRC).Methods 42patientswithrenaltumor,including 25caseswithfpAMLand17caseswithCCRC,wereretrospectivelyanalyzed.Allofthem werescannedinGSImode.Themorphology differencesbetweenthefpAMLgroupandtheCCRCgroupwereanalyzed.GSIViewersoftwarewasusedtocalculatetheiodineconcentration (IC),thenormalizediodineconcentration(NIC),thesloperateofthespectrumenergycurveinthecorticalphase(CP)andmedullaryphase (MP),respectively.Thedifferencesofthoseparameterswerecomparedbetweenthetwogroupsusingthetwo-simplettest.Results Somecharacteristicsigns,suchas"blackspots"sign,cracksignandnecrosishadthevaluefordifferentialdiagnosis.IntheCP,theIC ofthefpAMLandCCRCgroupwere30.20±5.25vs19.97±4.01,theNICswere0.45±0.10vs0.32±0.06,andthesloperatesof spectrumenergycurveswere3.45±1.23vs2.42±0.48,respectively.IntheNP,theICofthefpAMLandCCRCgroupwere27.84± 8.07vs22.94±4.46,theNICswere0.58±0.17vs0.46±0.11,andthesloperatesofthespectrumenergycurveswere3.24±1.25vs 2.69±0.47,respectively.Thereweresignificantdifferencesbetween2groups(P<0.05).TheNICintheCPprovidedhighsensitivity (75%)andspecificity(86%)indifferentiatingfpAMLfrom CCRC,andtheareaundertheROCcurvewas0.886.Conclusion The focalcysticandnecrotic,enhanceduniformityanddegree,"blackspots"sign,cracksignand multi-parametersofGSI,includingIC, NIC,andthesloperateofthespectrumenergycurvecouldplayimportantroleindifferentialdiagnosisbetweenfpAMLandCCRC.

Objective To explore the clinical value of 3D fast spin echo with an extended echo train acquistion (CUBE) T1WI enhancement sequence for purulent meningitis by comparing to contrast?enhanced T2WI?FLAIR sequence in the detection of lesions. Methods From August 2016 to July 2017, children with clinically suspected purulent meningitis underwent cranial magnetic resonance examination in our hospital. There were 35 children, 19 males and 16 females, aged 2 months to 3 years (median age 8 months) in total.A GE Discovery MR 750 3.0 T scanner was used to perform routine plain and enhanced scan in all children. After enhancement, the sequences of CUBE T1WI and FLAIR T2WI were applied randomly. Using the FLAIR T2WI enhancement sequence as the reference, we evaluated the detection rate of CUBE T1WI enhancement sequence for dura mater and leptomeningeal thickening. The number of enhanced lesions detected was tested by χ2 test. Results The enhanced FLAIR T2WI sequence showed 21 cases with dural enhancement, showing a rate of 60.0%. The enhanced CUBE T1WI sequence showed 31cases with dural enhancement, showing a rate of 88.6%. There were significant differences between the dural lesions detected(χ2＝6.058, P<0.01). The enhanced FLAIR T2WI sequence showed 16 cases of leptomeningeal enhancement,showing a rate of 45.7%. The enhanced CUBE T1WI sequence showed 19 cases of leptomeningeal enhancement,showing a rate of 54.3%.The enhanced CUBE T1WI sequence was not significantly higher than that of enhanced T2WI?FLAIR sequence in displaying leptomeningeal enhancement (χ2=0.229, P>0.05). Conclusion Enhancement of the CUBE T1WI sequence enables better visualization of meningeal thickening than FLAIR T2WI. It has great clinical value in the diagnosis of purulent meningitis in children.

Objective To investigate correlation between QT interval(QT),corrected QT interval(QTc) and metabolic syndrome(MS). Methods Residents who participated in our survey concerning atherosclerosis and related diseases conducted in Shenyang were included. They accomplished questionnaire,physical examination, laboratory tests and electrocardiography test. We divided them into MS group and non-metabolic syndrome (NMS)group according to International Diabetes Federation(IDF)diagnostic criteria for MS. QT interval was measured from the standard 12-lead electrocardiogram. QTc was calculated by using Bazett and Fridericia equations. We analyze correlation of QT ,QTc and MS. Results A total of 739 residents who were 35~64 years old were included. Individuals with MS had longer QTcB and QTcF than NMS group[(415.8 ± 31.9)ms vs.(410.1 ± 32.1)ms, (407.2± 29.1)ms vs.(402.6 ± 28.8)ms,P<0.05]. The more the number of abnormal MS parameters they had, the longer the QT,QTcB and QTcF they had. Regression analysis showed that QT was associated with serum potassium,smoking,blood glucose,and LDL,and QTcB and QTcF were associated with hypertension,waist circumference and blood potassium. Conclusions MS is associated with corrected QTc. Careful ECG monitoring among persons with MS for early detection of a long corrected QT interval may prevent severe and often fatal arrhythmias or sudden death.

Ubiquitination is one of the most major post-translational modifications playing important role in regulation of intra-cellular proteins' stability, degradation, localization and biological activity. However, these proteins are difficult to be detected due to their low abundance, short half-life. In this study, ubiquitin-binding domains (UBDs) were constructed to purify the ubiquitinated proteins from Hep3B cells. Ubiquitinated proteins and sites were detected by LC-MS/MS. A total of 1 900 potential ubiquitinated proteins were identified. Among them, 158 ubiquitinated sites were identified, belonging to 102 proteins. Bioinformatics analysis revealed that the enriched pathways of ubiquitinated proteins were closely related to tumor occurrence and development. The dysfunction of ubiquitin-proteasome has a high correlation with cell signaling and extracellular matrix changing in tumor cells.

Objective To identify the mediators of CDC42 signaling pathway involved in hepatitis B virus X protein (HBx)-mediated cellular transformation.Methods The mass defect-based pseudo-isobaric dimethyl labeling method (pIDL)was used to detect the differentially expressed proteins with a deficiency of CDC42.Furthermore,we conducted a gene ontology (GO)of differentially expressed proteins.Results and Conclusion We totally qualified 3409 proteins and found 220 differentially expressed proteins.Palladin,formin-like 1 (FMNL1)and keratin-19,which were implicated in cytoskeleton organization,were down-regulated with the deficiency of CDC42.Our results have provided candidate genes and proteins that may play an important role in HBx-mediated cellular transformation.

Auto liver transplantation (ALT) is a treatment option for patients with liver space-occupying lesion that could not be removed by conventional surgery and severe liver trauma,which also helps alleviate the shortage of donor liver.But many problems like the preoperative assessment,the tolerance of patients to surgery and anesthesia,delayed postoperative recovery of the liver function,primary non-function,liver failure and hepatic encephalopathy and even death still need to be addressed.Thus,it is particularly important to evaluate the operative indication,completely and accurately assess the preoperative liver function and liver function reserve,and reduce the perioperative mortality and complication in order to improve the prognosis of ALT.Combined with literalure and the experience in our center,this paper summarized the research advance of preoperative assessment in patients with ALT.

Due to the features of strong heterogeneity,difficult early diagnosis,poor prognosis,and high fatality rate,hepatocellular carcinoma (HCC) has become an important disease which threatens the health of the Chinese population.Accurate early diagnosis is crucial to improving the success rate of liver cancer resection and reducing postoperative recurrence and metastasis,and its core is the screening and validation of biomarkers for early diagnosis.Isobaric tags for relative and absolute quantitation (iTRAQ) and stable isotope labeling with amino acids in cell culture are important parts of proteomics technology,and iTRAQ has become the most important technique in quantitative proteomics technology due to its advantages of high throughput,high quantitative accuracy,and no limitation by sample source.This article reviews the research advances in molecular mechanism of the development and progression of HCC and screening of markers,in order to establish a theoretical foundation for in-depth understanding of the molecular mechanisms of the development and progression of HCC and the development of new biomarkers.