Leucine-rich repeats containing 4 protein (LRRC4) in memory, psychoneurosis, and glioblastoma / 中华医学杂志(英文版)

Leucine-rich repeats containing 4 ( LRRC4 , also named netrin-G ligand 2 [NGL-2]) is a member of the NetrinGs ligands (NGLs) family. As a gene with relatively high and specific expression in brain, it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas, thus being involved in gliomagenesis. LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma (GB) cells, including LRRC4/NGL2-activator protein 2 (AP2)-microRNA (miR) 182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1 (DNMT1)-LRRC4/specific protein 1 (SP1)-DNMT1-LRRC4. In this review, we demonstrated LRRC4 as a new member of the partitioning-defective protein (PAR) polarity complex that promotes axon differentiation, mediates the formation and plasticity of synapses, and assists information input to the hippocampus and storage of memory. As an important synapse regulator, aberrant expression of LRRC4 has been detected in autism, spinal injury and GBs. LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.

Research progress on hyperthermia in the treatment of glioma / 中华放射肿瘤学杂志

Glioma is a highly common malignant brain tumor. Current mainstream treatments include surgery, radiotherapy and chemotherapy, but the low survival rate and poor prognosis of patients have led scientists to explore new therapies. Hyperthermia is a method of local or whole body heating that utilizes high temperature to kill tumor cells to achieve a therapeutic effect, which has multiple advantages in the treatment of glioma, such as minimal invasiveness and high precision, etc. Studies have shown that hyperthermia combined with radiotherapy and chemotherapy can improve the clinical prognosis of patients. Currently, it serves as a therapeutic tool for glioma with huge potential advantages. In this review, the hyperthermia methods applied to treat glioma were introduced. The application prospects and current status of hyperthermia in treating glioma were summarized. In addition, the mature equipment and operation methods that have been applied in the hyperthermia treatment of glioma were illustrated.

Correlation between carotid plaque vulnerability and MRI overall burden of cerebral small vessel disease / 国际脑血管病杂志

Objective@#To investigate the correlation between carotid plaque vulnerability and MRI imaging markers and overall burden of cerebral small vessel disease (CSVD).@*Methods@#From January 2018 to December 2018, patients with carotid plaque thickness ≥2 mm admitted to the Brain Disease Center, the Affiliated Hospital of Nanjing University of Chinese Medicine was enrolled prospectively. Contrast-enhanced ultrasonography (CEUS) was used to evaluate the vulnerability of carotid plaque. All patients underwent head MRI. Lacunar infarction, white matter hyperintensities, cerebral microbleeds and enlarged perivascular space were recorded and the overall burden of CSDV was calculated. Binary multivariate logistic regression analysis was used to determine the correlation between carotid vulnerable plaque and various imaging markers of CSVD. Ordinal multivariable logistic regression analysis was used to determine the correlation between the carotid vulnerable plaques and the overall burden of CSCD.@*Results@#A total of 112 patients were included, including 61 (54.5%) in vulnerable plaque group and 51 (45.5%) in non-vulnerable plaque group. There were significant differences in the proportion of diabetes mellitus (49.2% vs. 19.6%; χ2=10.580, P<0.001), lacunar infarction (54.1% vs. 31.4%; χ2=5.829, P=0.016) and white matter hyperintensities (41.0% vs. 19.6%; χ2=5.907, P=0.015) between the vulnerable plaque group and the non-vulnerable plaque group. Multivariate logistic regression analysis showed that after adjusting for age, gender, hypertension, diabetes, and hyperlipidemia, there was a significant independent correlation between lacunar infarction (odds ratio [OR] 2.776, 95% confidence interval [CI] 1.139-6.765; P=0.025) and white matter hyperintensities (OR 3.969, 95% CI 1.465-10.753; P=0.007) and carotid vulnerable plaque. There were significant differences in age (F=4.275, P=0.003), past stroke history (χ2=11.100, P=0.025) and vulnerable plaque (χ2=9.829, P=0.043) in different CSVD burden groups. The overall burden of CSVD increased significantly with the increase of CEUS grade of carotid plaque (χ2=28.525, P=0.005). Ordinal multivariable logistic regression analysis showed that after adjusting for age, gender, hypertension, diabetes, coronary heart disease, stroke history, and smoking, there was still a significant independent correlation between the overall burden of CSVD and vulnerable plaques (OR 3.753, 95% CI 1.678-8.392; P=0.001).@*Conclusions@#Carotid vulnerable plaques were independently associated with lacunar infarction, white matter hyperintensities, and total burden of CSVD.

Correlation between carotid plaque vulnerability and MRI overall burden of cerebral small vessel disease / 国际脑血管病杂志

Objective To investigate the correlation between carotid plaque vulnerability and MRI imaging markers and overall burden of cerebral small vessel disease (CSVD).Methods From January 2018 to December 2018,patients with carotid plaque thickness ≥2 mm admitted to the Brain Disease Center,the Affiliated Hospital of Nanjing University of Chinese Medicine was enrolled prospectively.Contrast-enhanced ultrasonography (CEUS) was used to evaluate the vulnerability of carotid plaque.All patients underwent head MRI.Lacunar infarction,white matter hyperintensities,cerebral microbleeds and enlarged perivascular space were recorded and the overall burden of CSDV was calculated.Binary multivariate logistic regression analysis was used to determine the correlation between carotid vulnerable plaque and various imaging markers of CSVD.Ordinal multivariable logistic regression analysis was used to determine the correlation between the carotid vulnerable plaques and the overall burden of CSCD.Results A total of 112 patients were included,including 6l (54.5％) in vulnerable plaque group and 51 (45.5％) in non-vulnerable plaque group.There were significant differences in the proportion of diabetes mellitus (49.2％ vs.19.6％;x2 =10.580,P ＜ 0.001),lacunar infarction (54.1％ vs.31.4％;x2 =5.829,P =0.016) and white matter hyperintensities (41.0％ vs.19.6％;x2 =5.907,P=0.015) between the vulnerable plaque group and the non-vulnerable plaque group.Multivariate logistic regression analysis showed that after adjusting for age,gender,hypertension,diabetes,and hyperlipidemia,there was a significant independent correlation between lacunar infarction (odds ratio [OR] 2.776,95％ confidence interval [CI] 1.139-6.765;P =0.025) and white matter hyperintensities (OR 3.969,95％ CI 1.465-10.753;P =0.007) and carotid vulnerable plaque.There were significant differences in age (F =4.275,P =0.003),past stroke history (x2 =11.100,P =0.025) and vulnerable plaque (x2 =9.829,P=0.043) in different CSVD burden groups.The overall burden of CSVD increased significantly with the increase of CEUS grade of carotid plaque (x2 =28.525,P =0.005).Ordinal multivariable logistic regression analysis showed that after adjusting for age,gender,hypertension,diabetes,coronary heart disease,stroke history,and smoking,there was still a significant independent correlation between the overall burden of CSVD and vulnerable plaques (OR 3.753,95％ CI 1.678-8.392;P =0.001).Conclusions Carotid vulnerable plaques were independently associated with lacunar infarction,white matter hyperintensities,and total burden of CSVD.

Dose issue of novel oral anticoagulants to prevent stroke in patients with atrial fibrillation / 国际脑血管病杂志

Oral anticoagulants are important for preventing stroke in patients with atrial fibrillation.Compared with the traditional oral anticoagulant warfarin,the novel oral anticoagulants (NOACs) have the characteristics of high efficiency,safety,and no need to monitor coagulation function.However,current clinical reports have showed that the dose is usually low when NOACs were used for preventing stroke in patients with atrial fibrillation.Its main reason may be associated with the risk avoidance and the difference in doctor and patient preferences.The analysis from the aspects of safety and effectiveness,the risk of ischemic stroke or systemic embolism is lower when the dose of NOACs is relatively high,and the risk of hemorrhage is lower when the dose of NOACs is relatively lower.Given the differences between the incidences of different events,the disability rate and the mortality rate,the patient with atrial fibrillation are more suitable for using high-dose drug.When choosing a specific dose,taking into account the specificity,the appropriate dose,intensity,and dosing regimen should be given according to the guideline recommendations,appropriate reference to renal function and patient preferences,and individual differences in order to obtain the best clinical efficacy..

New routes of clinical medical English teaching for postgraduates in university of traditional Chinese medicine / 中华医学教育探索杂志

In order to realize the sustained education concept in clinical medical English teaching,several measures were taken in the first clinical medical college of Nanjing University of Traditional Chinese Medicine,such as training the teaching staff,using original textbooks and redesigning the curriculum.Particularly the tutorial system was introduced to the education frame.The teaching and research section of clinical medical English explored the new teaching routes for postgraduates in traditional Chinese medicine university.

Transcriptomic regulation and molecular mechanism of polygenic tumor at different stages / 中南大学学报(医学版)

The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.

Progress in LRRC4, a Novel Brain-specific Gene/Glioma Suppressive Gene / 生物化学与生物物理进展

LRRC4, a novel member of LRR (leucine-rich repeat) superfamily, is cloned by expressed sequence tag (EST)-mediated positional cloning strategy combined with 5′-RACE technology. Normal expression of LRRC4 is highly specific for brain, whereas absent or significantly down-regulated in primary tumors including glioma, meningioma and pituitary adenoma. LRRC4 is a functional gene in neural development and axon growth, and associated with glioma grade progression. LRRC4 expression is gradually reduced, even absent accompany with glioma grade increase. Absent expression of LRRC4 is involved in the late event of malignant glioma progression.The reexpression of LRRC4 can decrease a series of growth factors/neurotrophic factors (IGF, EGF, PDGF, CNTF, bFGF,GDNF and BDNF) or receptors gene expression to regulate RTK-mediated many signaling transduction pathway, such as K-Ras/c-Raf/ERK/MAPK, PI-3K/AKT/NF-?B, p70S6/PKC, STAT3 and JNK2/c-Jun/mp53, which block U251 cells in late phase of G1 to inhibit glioma cells proliferation and invasion. This inhibitory effect of LRRC4 is dependent on its LRR domain. LRRC4 induces glioma cells to differentiate into astrocyte-like cells more than apoptosis.

The Present and Advance in Transcriptomics of Nasopharyngeal Carcinoma / 生物化学与生物物理进展

Transcriptomics studies the variety, structure, function and regulation of all transcripts in a given cell and in a given time. It provides a novel procedure for revealing the molecular mechanism and regulatory network of different development stages of nasopharyngeal carcinoma. The progress of isolation, identification and function study of tumor susceptibility/suppressor gene, gene transcription profiling and transcription regulatory networks have been introduced.

The Depressant Effect on Lewis Lung Carcinoma and the Effect on the Expression of VEGF by Melting Agent of Anti-lung Cancer(MAALC) / 浙江中医药大学学报

[Objective] To study the effect on the growth of mouse Lewis lung carcinoma and on the expression of VEGF in tumor tissue.[Methods] C57BL/6 mice were inoculated the Lewis lung carcinoma cell at right armpit and divided into groups.Different groups were administered by MAALC(low,normal and high dose),CTX or saline.After 15 days,all mice were put to death to detach the tumors then weighed them.After that,we treated tumor tissue with VEGF immunohistochemistry stain,detected the integral optical density of VEGF expression with image analytical technique.[Results] Compared with model group,the average weight and VEGF expression level of the tumors of the high dose group were less and statistically significant(P

Experimental study of HL-60 cell differentiation induced by diallyl disulfide / 中国药理学通报

AIM To investigate the proliferation inhibition and inducing differentiation effect of diallyl disulfide (DADS) on human acute myeloid cell line HL 60. METHODS Inhibition of HL 60 cell proliferation was shown by MTT assay; cell differentiation was determined by morphologic observation,the ability of NBT reduction activity and flow cytometric detection. RESULTS DADS has significant anti proliferative effect on HL 60 cells in a concentration dependent manner. The reduction ability of NBT and cell surface differentiation antigens CD11b had significantly increased( P

Construction of differentially expressed cDNA library in human leukemia HL-60 cells induced by diallyl disfuld with suppression subtractive hybridization / 中国药理学通报

AIM To construct differentiation subtractive cDNA library of human leukemia HL 60 cells induced by diallyl disfuld using suppression subtractive hybridization (SSH) technique and to clone differentiation associated genes in leukemia cells. METHODS Poly A + RNAs were isolated from HL 60 cells induced by dially disfuld and were reversely transcripted into double strand cDNAs (as tester). After the cDNAs were digested into short cDNAs with blunt ends, they were divided into two groups and were ligated to the special adaptor 1 and adaptor 2R, respectively. The tester cDNAs were then hybridized with driver cDNA from normal HL 60 cells and the products were amplified twice by nested PCR technique. The PCR products were ligated with pGEM T plasmid vectors and were transformed into E.coli JM109. The inserts of cDNAs were analyzed by restrictive enzyme EcoR I. RESULTS Subtractive cDNA library was constructed successfully and efficiently. Random analysis of 200 clones with enzyme restriction showed that about 84 5% clones contained 100～600 bp cDNA inserts. It can help clone novel genes associated with differentiation and explore the molecular mechanism of leukemia differentiation induced by diallyl disfuld. CONCLUSION DADS can induce human leukemia HL 60 cells differentiation, and suppression subtractive hybridization (SSH) technique is an effective method to isolate those differentially expressed genes.

Induction of differentiation by diallyl disulfide through inhibition of JAK1/STAT3 in human leukemia HL-60 cells / 中国药理学通报

Aim To investigate JAKs/STATs signal transduction change in HL-60 cells differentiation induced by diallyl disulfide(DADS)and molecular mechanism regulating the differentiation.Methods After incubation of HL-60 cells with DADS or AG490(50 ?mol?L -1),the cell differentiation indexes were observed by cytomorphology, NBT reduction ability assay,cell myeloid differentiation antigen CD11b by flow cytometry. Kinase activity of JAKs/STATs was tested by western-blotting and expressions of nucleus transcription genes stats,c-myc,c-fos,c-jun were detected by immumocyte chemistry method.Results Cell differentiation index changes indicated that HL-60 cells were induced differentiation toward granulocytic lineage by DADS, Western blot test demonstrated that constitive phosphorylation of Jak1,stat3 kinase was suppressed. Stat3,c-myc gene expression decreased and c-fos, c-jun gene expression increased in HL-60 cells treated with DADS through immunocyte chemistry.Conclusion Inhibition of phosphative Jak1, Stat3 was involved in HL-60 cells differentiation induced by DADS, its molecular mechanism might be related to modulation of gene expression associated proliferation and differentiation,and inhibition of DNA systhesis, induction differentiation.