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 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.

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].

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.