Objective:To investigate the differences in the expression levels of miR-196a-5p and miR-105-5p in serum of patients with benign and malignant pulmonary nodules and their diagnostic value of malignant pulmonary nodules.Methods:The expression levels of miRNAs in cancer tissues of lung adenocarcinoma and lung squamous cell carcinoma and paracancerous tissues in The Cancer Genome Atlas (TCGA) database were analyzed, and the miRNAs with significantly different expression levels in cancer tissues and paracancerous tissues were selected as target miRNAs. A total of 72 patients with pulmonary nodules admitted to Weifang People′s Hospital of Shandong Province from June 2019 to July 2020 were selected. The expression levels of target miRNAs in serum of patients with pulmonary nodules were detected by qRT-PCR. Receiver operating characteristic (ROC) curve was used to compare the diagnostic value of target miRNAs with tumor markers Cyfra21-1, NSE and CEA in malignant pulmonary nodules.Results:After screening, the target miRNAs were identified as miR-196a-5p and miR-105-5p. Twenty-six patients in the benign pulmonary nodules group and 46 patients in the malignant pulmonary nodules group were included. The levels of serum miR-196a-5p [ M ( P25, P75)] in the benign and malignant nodules group were 0.63 (0.09, 2.15) and 1.93(0.93, 4.97) respectively, and the levels of miR-105-5p in the two groups were 2.03 (0.54, 7.95) and 10.65 (5.94, 18.39) respectively. Compared with the benign pulmonary nodules group, the levels of serum miR-196a-5p and miR-105-5p in the malignant pulmonary nodules group were increased, and there were statistically significant differences ( Z=-3.083, P=0.002; Z=-4.092, P<0.001). The levels of serum Cyfra21-1 in the benign and malignant pulmonary nodules group were 2.48 (1.84, 3.78) and 2.20 (1.47, 3.32) μg/L respectively, the levels of serum NSE in the two groups were 15.58 (12.45, 18.95) and 14.43 (12.07, 17.87) μg/L respectively, and the levels of serum CEA in the two groups were 1.16 (0.55, 2.11) and 1.17 (0.61, 1.68) μg/L respectively. There were no significant differences in serum Cyfra21-1, NSE and CEA between the benign and malignant pulmonary nodules group ( Z=-1.161, P=0.246; Z=-0.305, P=0.761; Z=-0.271, P=0.786). The area under the curve (AUC) of the combination of miR-196a-5p and miR-105-5p for the diagnosis of malignant pulmonary nodules was 0.762 (sensitivity 89.1%, specificity 61.5%), which was higher than the value of the combination of Cyfra21-1, NSE and CEA for the diagnosis of malignant pulmonary nodules (AUC=0.591, sensitivity 58.7%, specificity 64.5%). Conclusion:The combination of serum miR-196a-5p and miR-105-5p can assist in the diagnosis of malignant pulmonary nodules and has higher diagnostic value.

The incidence of liver disease is increasing year by year. Due to the complex predisposing factors and unclear pathogenesis of liver diseases, the cure rate is still not ideal, so it is urgent to clarify its mechanism to find more effective therapeutic targets and drugs. Long non-coding RNA (lncRNA), as a non-coding RNA with a length of more than 200 nt, is a research hotspot in liver diseases in recent years. Focusing on the main signal transduction pathways in liver diseases, this review mainly summarizes the latest research progress of lncRNA in regulating liver disease-related signaling pathways, and elaborates that lncRNAs participate in various physiological processes such as cell proliferation, apoptosis, invasion, and migration by regulating key signaling pathways in liver diseases, thereby promoting the occurrence and development of liver diseases. This review provides new ideas for studying the mechanism of liver diseases, and new directions for finding new targets and biomarkers for the treatment of liver diseases.

Objective ToexploretheMRIfeaturesanddifferentialdiagnosisofgemistocyticastrocytoma(GemA).Methods The MRIfeaturesof10casesofGemAprovedbysurgeryandpathologywereinvestigatedretrospectively(thelocationoftumor,tumor shape,boundary,signalandenhancement)andtheliteraturewasreviewed.Results All10casesofGemA weresupratentorialand solitary.Ofthese10cases,7caseswerelocatedinthefrontallobe,5casesinthetemporallobe,6casesinmultiplelobesandinvaded theoppositebraintissuesthroughcorpuscallosum.8casesweresolidGcystic,8casespresentedwithunclearboundary,only2cases hadclearboundary.Therewasnoedemaormildedemain7casesandobviousedemain3cases.Thesolidpartoftumorswereisointense orslighthypointenseonT1WI,only1caseshowedhighintensityonT1WI,isointenseorslighthyperintenseonT2WI.CTsuggested calcificationin2cases.6casesweremildlyenhanced,4casesweremarkedlyenhanced.MRSshowed(n＝4)thatCHopeakwasmildly ormoderatelyincreased,NAApeakwassignificantlyreduced,theaverageratioofCho/NAA was2.91.DWIshowedhyperintenseor slighthyperintense(n＝3),theADCaveragevalueoftumorROIwasabout(1.150±0.081)×10－3 mm2/s.1caseofSWIsequence showedthickeningandcircuitousvascularshadow.Conclusion AsMRIofGemAischaracterizedbyhighandlowgradegliomas,the preoperativediagnosisisdifficult.Combiningenhancementwithfunctionalexamination,itisexpectedtoimprovetheaccuracyofpreoperative diagnosisofGemA.

Objective To explore the MRI findings of diffuse midline gliomas with H3K27M mutation, and help us understand this new entity and improve the accuracy of diagnosis. Methods The clinical and imaging data of 17 diffuse midline gliomas with H3K27M mutation confirmed by pathology were retrospectively collected from July 2016 to April 2018 in Guangdong Sanjiu Brain Hospital. All patients were performed with pre?contrast and post?contrast MRI examination. All images were analyzed according to the location, shape, boundary, solid or cystic, signal feature, enhancement feature, and degree of edema. Results (1) Location:Six cases located in thalamus,4 cases located in brainstem,1 located in hypothalamus, 6 cases had multiple lesions in the midline and/or involving one or more brain. (2) Morphology and boundary:Seven cases had regular shape and clear boundary, 10 cases had irregular shapes and unclear boundaries. (3) Necrosis, cystic degeneration, hemorrhage: Twelve cases had necrosis or cystic degeneration in varying degree, 4 cases had hemorrhage. (4) Signal and enhancement features: The solid component showed slightly?low or low signal on T1WI, and slightly?high or high signal on T2WI; the cystic component showed obvious low signal on T1WI and obvious high signal on T2WI. T1WI enhancement:Eight cases showed uneven light?moderate enhancements, and all cases were adults; Six cases showed significant enhancements with large or small rings; Three cases showed uneven obvious enhancement. (5) Peritumoral edema: Fourteen cases had mild peritumoral edema,1 case had moderate peritumoral edema,2 cases had obvious peritumoral edema. Conclusion The MRI findings of diffuse midline gliomas with H3K27M mutation had certain characteristics,which can help to improve the level of diagnosis and differential diagnosis.

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.

OBJECTIVETo investigate the antineoplastic effects of 2-Deoxy-D-glucose (2-DG) combined with Taxol on orthotopically transplanted breast cancer in C3H mice and explore the mechanism.

METHODSC3H mice bearing orthotopically transplanted breast cancer xenograft were randomly divided into 4 groups, namely the control group, 2-DG group, Taxol group, and 2-DG+Taxol group. The corresponding drugs were administered intraperitoneally every 3 days for 18 consecutive days, and the tumor volume was measured every 3 days to draw the tumor growth curve. The mice were then sacrificed to measure the tumor weight on day 19 and examine tumor cell apoptosis with TUNEL assay and VEGF expression using immunohistochemistry.

RESULTS2-DG combined with Taxol obviously suppressed the tumor growth with a tumor inhibition rate of 66.06% as compared to the rate of 36.97% in Taxol group. The combined treatment also caused more obvious cell apoptosis and significantly reduced VEGF expression in the tumor cells as compared with the other groups.

CONCLUSION2-DG can enhance the inhibitory effect of Taxol on orthotopically transplanted breast cancer xenograft in C3H mice probably by inducing tumor cell apoptosis and lowering VEGF expressions.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; Breast Neoplasms ; drug therapy ; pathology ; Cell Line, Tumor ; Deoxyglucose ; pharmacology ; therapeutic use ; Drug Synergism ; Female ; Mice ; Mice, Inbred C3H ; Paclitaxel ; pharmacology ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

Objective:To investigate the regulatory effects of sphingosine kinase-2 (SphK2) on the function of activated astrocytes and the progression of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:Primary mouse astrocytes were isolated from wild-type (WT) C57BL/6 mice and sphk2 gene knock-out ( sphk2 -/-) mice and stimulated in vitro with interleukin 17 (IL-17). Real-time PCR was used to measure the expression of inflammatory cytokines and chemokines at mRNA levels. Western blot and immunofluorescence were used to detect the expression of glial fibrillary acidic protein (GFAP) and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). An EAE mouse model was constructed using myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) polypeptide. Western blot was used to detect the expression of GFAP and p-STAT3 at protein level and real-time PCR was used to detect the expression of inflammatory cytokines and chemokines at mRNA level in spinal cords. Hematoxylin-Eosin (HE) and Luxol fast blue (LFB) staining were used to observe the changes in inflammatory cell infiltration and demyelination in spinal cords. Results:Compared with the WT group, the phosphorylation of STAT3 was obviously reduced in in vitro activated mouse astrocytes of sphk2 -/- mice, and the expression of inflammatory cytokines and chemokines including monocyte chemotactic protein 1 (MCP-1), TNF-α and IL-6 at mRNA level was also significantly decreased. Compared with the WT EAE group, changes in the above-mentioned cytokines and relative proteins in sphk2 -/- EAE mice in vivo were similar to those in vitro. Moreover, inflammatory cell infiltration and demyelination were significantly reduced in spinal cords of sphk2 -/- EAE mice. However, no significant difference in in vitro or in vivo GFAP expression was observed between WT and sphk2 -/- mice. Conclusions:SphK2 might regulate the function of reactive astrocytes through STAT3 molecular pathway, thereby regulating the production of inflammatory cytokines and chemokines and participating in the pathological process of EAE.

Objective:Heme chloride(Hemin)is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs.This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice,and explore its role in anti-plateau hypoxia. Methods:Thirty male BALB/c mice were randomly divided into a blank group,a positive drug group(acetazolomide,200 mg/kg),a Hemin low-dose group(15 mg/kg),a Hemin medium-dose group(30 mg/kg),and a Hemin high-dose group(60 mg/kg)with intraperitoneal injection.The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened.Thirty-six male BALB/c mice were randomly divided into a blank group,a hypoxia group,a positive drug group,and a Hemin high-dose group.The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde(MDA),glutataione(GSH),and superoxide dismutase(SOD)levels of myocardium,brain,lung,and liver tissues were measured in different groups with hypoxia for 24 h.The degree of histopathological damage of mice was observed with HE staining.The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole. Results:Compared with the blank group,the survival time of mice in the positive drug group,the Hemin medium-dose group,and high-dose group was significantly extended(all P<0.05),with the highest prolongation rate in the Hemin high-dose group.Compared with the hypoxia group,mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue,and a significant decrease in MDA content of lung tissue(all P<0.05).The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver,heart,brain and lung tissues of mice with hypoxia,and the most obvious effect on that of the brain tissue. Conclusion:Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia,and has obvious protective effect on tissue damage caused by hypoxia.

As one of the pathogenic mechanisms contained in The Inner Canon of Yellow Emperor （《黄帝内经》）， “disease with latent pathogen induced by a new pathogen” means that the induced new pathogen resulted to a combination of the latent previous pathogen and the new pathogen， which caused the disease. Based on this， it is believed that the change of “nodule-cancer transformation” of pulmonary nodules is actually based on the deficiency of original qi， and the new pathogen induces the latent pathogens like phlegm coagulation， qi stagnation， blood stasis， toxicity， so healthy qi can not drive the pathogens out， and the long-time detention generated into cancerous turbidity， and deve-loped into cancerous tumour at the end. Therefore， based on the three-stage treatment of unformed cancer， dense cancerous toxin， and developed cancer， the clinical practice applied six methods of clearing， expelling， dissipating， tonifying， harmonizing， and transforming， taking into account both the manifestation and root cause， moving the treatment window of pulmonary nodules forward， attacking the pathogens when the toxin was not yet overbearing， supporting the healthy qi before declining， delaying the process of nodules-cancer transformation， and providing ideas for the prevention and treatment of pulmonary nodules “nodule-cancer transformation” in traditional Chinese medicine.

Tibetan is a kind of medicine which extensively absorbed and fused the Chinese Traditional Medicine, Indian medicine and food through long-term practice and form the unique medical system. At the same time, the Qinghai Tibet plateau has characteristics of high altitude and lack of resources and oxygen, which has formed its unique geographical environment and grow a lot of rare medicinal plants. Tibetan medicine has a long history and is one of the relatively complete and influential ethnic medicines in China, which has played an important role in the treatment of plateau diseases. In recent years, with the increasing of economic activities in the plateau, the plateau anoxia had greatly affected the working capacity of the plateau. According to "Chinese medicine" through the literature, the pharmacological activities, active ingredients, growing environment of Tibetan medicine with good plateau hypoxia effect were reviewed and according to the site, which could be divided into the lung protection medicine, the cardiac protection medicine, the brain protection medicine, the liver protection medicine, the improvement of fatigue medicine and other medicine, which could provide theoretical basis for finding more potential anti-hypoxia drugs.