Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is a primary contributor to cancer-related mortality on a global scale.However,the underlying molecular mechanisms are still poorly understood.Long noncoding RNAs are emerging markers for HCC diagnosis,prognosis,and therapeutic target.No study of LINC01767 in HCC was published.AIM To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.METHODS DESeq2 Package was used to analyze different gene expressions.Receiver operating characteristic curves assessed the diagnostic performance.Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis.The least absolute shrinkage and selection operator(LASSO)-Cox was used to identify the prediction model.Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction,next generation sequencing was performed following LINC01767 over expression(GSE243371),and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out.In vitro experiment in Huh7 cell was carried out.RESULTS LINC01767 was down-regulated in HCC with a log fold change=1.575 and was positively correlated with the cancer stemness.LINC01767 was a good diagnostic marker with area under the curve(AUC)[0.801,95% confidence interval(CI):0.751-0.852,P=0.0106]and an independent predictor for overall survival(OS)with hazard ratio=1.899(95%CI:1.01-3.58,P=0.048).LINC01767 nomogram model showed a satisfied performance.The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways.LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC>0.75.LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line;the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro.CONCLUSION LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

Role and mechanism of circ-PRKCI in hepatocellular carcinoma

BACKGROUND The circular RNA circ-PRKCI is an endogenous non-coding RNA that forms a covalently closed ring after reverse splicing, which plays a key role in the occurrence and development of multiple digestive system tumors.AIM To investigate the role and mechanism of circ-PRKCI in the occurrence and development of hepatocellular carcinoma(HCC).METHODS This study used real-time polymerase chain reaction to detect the expression of circ-PRKCI in tumor tissues, tumor adjacent tissues, and blood in patients with HCC and other digestive system tumor cells. A series of functional tests were performed to explore whether circ-PRKCI affects the growth of HCC cells and what is its mechanism in HCC. Meanwhile, fluorescence in situ hybridization was used to detect the subcellular localization of circ-PRKCI. Survival analysis was performed to predict the correlation between circ-PRKCI and the prognosis of HCC. Chi-square test and t-test were performed for statistical analyses.RESULTS The level of circ-PRKCI was significantly higher in HCC tissues than in tumor adjacent tissues, and in HCC cell lines than in cells lines of esophageal, liver,stomach, and colon cancers. A series of functional tests showed that circ-PRKCI substantially inhibited cell apoptosis and promoted cell invasion. It was foundthat circ-PRKCI can act as the sponge of miRNA-545 to reduce the expression of AKT3 protein. Moreover, the result of survival analysis showed that circ-PRKCI target gene E2 F7 can reduce liver cancer patients' survival rate. And clinical data suggested that the distribution of circ-PRKCI rose with the depth of invasion,lymph node metastasis, distant metastasis, and TNM stage, indicating that circPRKCI may affect the survival and prognosis of patients with HCC by regulating E2 E7.CONCLUSION This study explores the role and mechanism of circ-PRKCI in HCC, which provides a new research direction and theoretical basis for the treatment of HCC.

A Bioassay for the Cytotoxicity of Gemcitabine Using the Marine Ciliate Euplotes vannus

This study investigated the cytotoxicity of gemcitabine using the marine ciliate Euplotes vannus as the test organism.The median lethal concentrations(LC50 values)were determined using acute toxicity tests within an exposure time of 30 min with 0,6,12,24,and 48 mg mL^-1 gemcitabine.The median inhibition effect(IC50 value)on the growth of the ciliate cells was examined using chronic toxicity tests within 5 days(120 h)after exposure for 30 min with 0,0.7,3.5,7,and 14 mg mL^-1 gemcitabine.The 30-min LC50value was 10.66-mg mL 1.The LC50 values decreased with increasing exposure times and well fitted to the toxicity curve equation LC50=10.93+28.4e^-0.19t(R2=0.93;P<0.05,t=exposure time).The IC50 value for growth rates was 7.05 mg mL^-1,and the inhibition effect on growth rates well fitted to the model equation r%=0.8681e^-0.0782Cgem(r%means growth rate with inhibition by gemcitabine,Cgem means concentrations of gemcitabine,R^2=0.99 and P<0.05).The LC50 values of a wide range of gemcitabine concentrations could therefore be predicted for any given exposure time.These results suggest that the clinical dose of gemcitabine(20 mg mL^-1)was higher than the 30-min LC50 value,which was almost the same as the 6-min LC50 value(19.88 mg mL^-1)for E.vannus cells.The results also demonstrate that E.vannus can be used as a robust test organism for bioassays of chemotherapeutic drugs during short exposure periods.

A Pharmacological Study on Action Mechanism of Zhizi Ganjiang Decoction from Treatise on Cold Damage Diseases in Treating Sleep Disorders

[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction(ZZGJD)regulating sleep disorders based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of ZZGJD and constructed a compound-disease-target network map,and the GeneCards database was used to search for insomnia-related targets;with the aid of Cytoscape 3.5.1 software,the compound-insomnia target interaction network and protein-protein interaction(PPI)network were constructed,and gene ontology(GO)enrichment,Reactome pathway enrichment,and biological pathway enrichment analysis based on KEGG(Kyoto Encyclopedia of Genes and Enomes)was performed.[Results]The constructed PPI network of ZZGJD involves 204 nodes and 645 interaction relationships.Key nodes involve G protein-coupled receptors,rhodopsin-like adrenaline receptor families,zinc finger proteins,nuclear hormone receptor superfamilies,ligand-binding domains of hormone receptors,voltage-gated calcium(Ca^(2+))channel IQ domains,and neuropituitary hormones.The related entries of GO enrichment analysis pathway mainly involve G protein-coupled receptor activity,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,catecholamine binding,G protein-coupled serotonin receptor activity,serotonin receptor activity,and steroid hormone receptors(SHRs)activity.Reactome pathway mainly involves amine ligand binding receptors,rhodopsin-like receptors,G protein-coupled receptor ligand binding,adrenergic receptors,neuronal systems and signal transduction,etc.KEGG channel analysis mainly involves neural activity ligand-receptor interaction,calcium ion messenger pathway,cAMP signaling pathway,serotonergic synapse,dopaminergic synapse,cGMP-PKG signaling pathway,and cholinergic synapse pathway,etc.[Conclusions]The potential targets of ZZGJD in the treatment of insomnia mainly involve G protein-coupled receptors,and regulate various neural receptor pathways such as calcium ion channels,serotonin,dopamine,and adrenergic receptors.INS,IGF-1,CTNNB1,ESR1,HIF-1A,etc.may be the key targets of ZZGJD in regulating sleep disorders,reflecting the multi-target and overall function characteristics of Chinese herbal compounds.ZZGJD is of great significance in the treatment of sleep disorders caused by blood sugar abnormality in patients with diabetes and perimenopausal hormones in women.This article is expected to It provide new ideas for in-depth study of the molecular mechanism of ZZGJD.

Gastric signet-ring cell carcinoma with paraneoplastic eosinophilia: A case report and literature review

We report the case of a 40-year-old female Chinese patient with gastric signet-ring cell carcinoma that was first diagnosed because of paraneoplastic eosinophilia.The patient’s eosinophil count reduced markedly to normal levels within 24 h after radical gastrectomy and Billroth II anastomosis.The patient recovered well after the surgery and no abnormalities were found during the regular follow-ups.Paraneoplastic eosinophilia is an unusual manifestation that usually remains asymptomatic;moreover,cases of solid malignant tumors with eosinophilia are uncommon.To our knowledge,this is the first reported case of paraneoplastic eosinophilia in a patient with gastric carcinoma.We considered eosinophilia as a manifestation of a paraneoplastic syndrome,which can be the first clinical manifestation of a malignancy.

Development and validation of a nomogram prediction model for the risk of parastomal hernia

Background Parastomal hernia is one of the potential complications after enterostomy.There is currently no early risk assessment tool for parastomal hernia.Methods The current investigation was conducted using retrospective studies.A total of 302 cases were used develop and internally to validate a nomogram prediction model,and 67 cases were used for external validation.Independent risk factors for parastomal hernia after permanent sigmoid colostomy were assessed via univariate analysis and binary logistic regression analysis.The nomogram prediction model was established based on independent risk factors.Results Body mass index,serum albumin,age,sex,and stoma diameter were independent risk factors for parastomal hernia.The areas under the receiver operating characteristic curves were 0.909 in the development group and 0.801 in the validation group.The Hosmer-Lemeshow test(P>0.05)and calibration curves indicated good consistency between actual observations and predicted probabilities.Conclusions A nomogram prediction model was constructed and validated based on risk factors for parastomal hernia.The nomogram could be generalized to patients undergoing surgery for stoma by specialized surgeons to provide relevant references for stoma patients.

Association between GABRG2 rs211037 polymorphism and idiopathic generalized epilepsies:a meta-analysis

Background:We performed this meta-analysis to investigate the association between GABRG2 rs211037polymorphism and the risk for idiopathic generalized epilepsies(IGEs).Methods:Medline,Embase,Cochrane Library and Chinese National Knowledge Infrastructure(CNKI)databases were searched for eligible studies(until May 5,2020)on the association between GABRG2 rs211037 polymorphism and IGE.The odds ratios were calculated using a fixed or random model in STATA 15.0 software.Subgroup analyses for ethnicity,age,source of controls,type of seizure syndrome and therapeutic responses were conducted.Results:We found no significant associations between GABRG2 rs211037 polymorphism and the susceptibility to IGEs.In addition,no significant association was detected between GABRG2 rs211037 polymorphism and drug resistance in IGE patients.The results did not change after stratification by Asian population,healthy controls,children,juvenile myoclonic epilepsy,and childhood absence epilepsy.Conclusion:The current studies indicated that the GABRG2 rs211037 polymorphism was not related to susceptibility or drug resistance of IGE.Further well-designed studies are needed to verify the results.

Analysis of the chemoprophylactic effect on close contacts of patients with active tuberculosis and positive tuberculin skin tests

Objective:The current study analyzed the chemoprophylactic effect of isoniazide on close contacts of patients with active tuberculosis and positive tuberculin skin tests(TSTs).Methods:A total of 1206 close contacts of patients with active tuberculosis and strongly-pos-itive TSTs were enrolled.The patients had chest X-ray examinations.Patients without tuberculosis and other diseases were divided into the following groups:90 patients in the prophylaxis group,who were given 300 mg of isoniazid qd(3-5 mg/kg for children)over a 10-month treatment course;and 89 patients in the control group without drug therapy.Both groups were followed for 10 years.Results:(1)There were 568 patients with negative results and 638 with positive results,includ-ing 445 with ordinarily-and moderately-positive results,and 193 with strongly-positive results(a positive rate of 52.9%[638/1206]and a strongly-positive rate of 16.0%[193/1206]).Fourteen tuber-culosis patients were identified(tuberculosis detection rate of 1.1%).(2)During the 3-year period of follow-up,there were 4 patients in the prophylaxis group and 12 patients in the control group who acquired tuberculosis(a morbidity rate of 4.7%[4/84]and 13.4%[12/89],respectively),and the dif-ference was statistically significant(χ^(2)=3.916,P=0.048).Six patients in the prophylaxis group,all of whom were children,discontinued medication use during the course of treatment due to adverse drug reactions,for an adverse drug reaction occurrence rate of 6.6%(6/90),a medication completion rate of 93.3%(84/90),and a 3-year protection ratio of 64.6%.(3)During the 4-6 year period,there were two patients in the prophylaxis group and three patients in the control group who acquired tubercu-losis(a morbidity rate of 2.5%[2/78]and 4.1%[3/73],respectively),two in the prophylaxis group and four in the control group who were lost to follow-up(a loss to follow-up rate of 2.5%[2/80]and 5.1%[4/77],respectively),and the difference was not statistically significant(χ^(2)=0.006,P=0.940;χ^(2)=0.215,P=0.643).(4)During the 7-10 year study,there was one patient in the prophylaxis group and two patients in the control group who acquired tuberculosis(a morbidity rate of 1.3%[1/72]and 3.1%[2/64],respectively),and four in the prophylaxis group and six in the control group who were lost to follow-up(a loss to follow-up rate of 5.2%[4/76]and 8.5%[6/70],respectively),and the dif-ference was not statistically different(χ^(2)=0.011,P=0.918;χ^(2)=0.176,P=0.675).(5)Within 10 years,there were 7 patients in the prophylaxis group and 17 patients in the control group who acquired tu-berculosis(a morbidity rate of 8.3%[7/84]and 21.5%[17/79],respectively;χ^(2)=4.770,P=0.029),and 6 in the prophylaxis group and 10 in the control group were lost to follow-up(the loss to follow-up rate was 7.1%[6/84]and 11.2%[10/89],respectively;χ^(2)=0.863,P=0.353).Conclusion:Close contacts of patients with active tuberculosis are at high-risk for acquir-ing tuberculosis.It is safe and effective for patients with strongly-positive TST results to undergo isoniazid chemoprophylaxis for 10 months.

SALIRI-based(raltitrexed plus irinotecan)therapy as a second-line treatment for patients with metastatic colorectal cancer(SALLY):A prospective,multicenter,non-interventional,registry study

Primary chemotherapy options for colorectal cancer(CRC)involve four key drugs:fluorouracils(5-FU),oxaliplatin,irinotecan and raltitrexed.The first-line regimen consists of 5-FU and leucovorin combined with oxaliplatin(FOLFOX),while the second-line regimen involves 5-FU and leucovorin combined with irinotecan(FOLFIRI)for metastatic CRC(mCRC)in China[1].