Prognostic implications and functional enrichment analysis of LTB4R in patients with acute myeloid leukemia / 南方医科大学学报

OBJECTIVE@#To explore the expression patterns, prognostic implications, and biological role of leukotriene B4 receptor (LTB4R) in patients with acute myeloid leukemia (AML).@*METHODS@#We collected the data of mRNA expression levels and clinical information of patients with AML from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database for mRNA expression analyses, survival analyses, Cox regression analyses and correlation analyses using R studio to assess the expression patterns and prognostic value of LTB4R. The correlation of LTB4R expression levels with clinical characteristics of the patients were analyzed using UALCAN. The co-expressed genes LTB4R were screened from Linkedomics and subjected to functional enrichment analysis. A protein-protein interaction network was constructed using STRING. GSEA analyses of the differentially expressed genes (DEGs) were performed based on datasets from TCGA-LAML stratified by LTB4R expression level. We also collected peripheral blood mononuclear cells (PBMCs) from AML patients and healthy donors for examination of the mRNA expression levels of LTB4R and immune checkpoint genes using qRT-PCR. We also examined serum LTB4R protein levels in the patients using ELISA.@*RESULTS@#The mRNA expression level of LTB4R was significantly increased in AML patients (4.898±1.220 vs 2.252±0.215, P < 0.001), and an elevated LTB4R expression level was correlated with a poor overall survival (OS) of the patients (P=0.004, HR=1.74). LTB4R was identified as an independent prognostic factor for OS (P=0.019, HR=1.66) and was associated with FAB subtypes, cytogenetic risk, karyotype abnormalities and NPM1 mutations. The co- expressed genes of LTB4R were enriched in the functional pathways closely associated with AML leukemogenesis, including neutrophil inflammation, lymphocyte activation, signal transduction, and metabolism. The DEGs were enriched in differentiation, activation of immune cells, and cytokine signaling. Examination of the clinical serum samples also demonstrated significantly increased expressions of LTB4R mRNA (P=0.044) and protein (P=0.008) in AML patients, and LTB4R mRNA expression was positively correlated with the expression of the immune checkpoint HAVCR2 (r= 0.466, P=0.040).@*CONCLUSION@#LTB4R can serve as a novel biomarker and independent prognostic indicator of AML and its expression patterns provide insights into the crosstalk of leukemogenesis signaling pathways involving tumor immunity and metabolism.

Pan-cancer analysis of the expression pattern of long non-coding RNA MIR22HG / 南方医科大学学报

OBJECTIVE@#To conduct a pan-cancer analysis of the expression of long non-coding RNA (lncRNA) MIR22HG and explore its association with clinical characteristics.@*METHODS@#We analyzed the expression of MIR22HG in different tumors and its association with clinical staging, lymph node metastasis, tumor mutation burden (TMB) and microsatellite instability (MSI) using R package based on the Cancer Genome Atlas (TCGA) datasets. The relationship between MIR22HG expression and infiltrating immune cells was analyzed using TIMER algorithm. The association of MIR22HG gene alteration frequency with the clinical outcomes was examined using cBioPortal online software. Data form Genomics of Drug Sensitivity in Cancer (GDSC) were used to analyze the relationship between MIR22HG and the sensitivity of chemotherapy drugs. We specifically analyzed MIR22HG expression in hepatocellular carcinoma (HCC) and its correlation with sorafenib treatment using GEO database and verified the results in 12 pairs of HCC specimens. Kaplan-Meier analysis was performed to analyze the correlation of MIR22HG with the outcomes of sorafenib treatment. We also tested the effects of MIR22HG overexpression and knockdown on IC50 of sorafenib in HCC cells.@*RESULTS@#MIR22HG was downregulated in most tumors (P < 0.05), where its deletion mutations were frequent, and associated with a poor prognosis (P < 0.05). In many tumors, MIR22HG expression level was correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, immune checkpoint-related genes, and sensitivity to common chemotherapeutic drugs (P < 0.05). Among the 6 common infiltrating immune cells in cancers, neutrophil infiltration had the strongest correlation with MIR22HG expression level, especially in breast cancer, rectal cancer and kidney renal papillary cell carcinoma (P < 0.05). MIR22HG was downregulated in HCC in association with HCC progression (P < 0.05). In HCC patients, a low MIR22HG expression was associated with a favorable outcome after sorafenib treatment (HR=2.94, P=0.075) and was capable of predicting the response to sorafenib treatment (AUC=0.8095). Compared with the negative control, MIR22HG overexpression obviously reduced sorafenib sensitivity (with IC50 of 7.731 vs 15.61) while MIR22HG knockdown increased sorafenib sensitivity of HCC cells (with IC50 of 7.986 vs 5.085).@*CONCLUSION@#MIR22HG expression level is correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, and chemosensitivity in most cancer, suggesting its potential as an immunotherapeutic target and also a prognostic biomarker for tumors.

Mechanism of Zhigancao Tang Against Coronary Heart Disease： An Exploration Based on Thought of "Four in One" / 中国实验方剂学杂志

"Four in one" is a research idea of identifying the classic prescriptions from the following four dimensions： "nature， location， tendency， and syndrome". The multi-dimensional analysis of the mechanism of classic prescription Zhigancao Tang in treating coronary heart disease helps to understand the syndrome differentiation and treatment thoughts of ZHANG Zhong-jing. The coronary heart disease results from deficiency. The efficacy of Zhigancao Tang in treating coronary heart disease can be elucidated from the "nature，location，tendency， and syndrome". In terms of nature， Zhigancao Tang is pungent and sweet in flavor and warm in property， with the sweet responsible for tonifying deficiency， the pungent for dispersing Yang， resolving Yin， and eliminating surplus pathogen， and the warm for moving Yangqi， nourishing blood， and promoting blood circulation. In terms of location， Zhigancao Tang mainly acts on vessels for restoring the normal circulation of blood in the vessels and improving coronary artery stenosis and the resulting ischemia and anoxia. In terms of tendency， Zhigancao Tang tends to affect the upper and inner parts of the body to tonify deficiency in Zangfu organs， promote fluid production， nourish nutrient blood， and dissipate cold simultaneously， thus alleviating chest impediment. In terms of syndrome， Zhigancao Tang is applicable to fluid exhaustion with blood dryness and Yin-yang-qi-blood deficiency syndrome， manifested as regularly or irregularly intermittent pulse and severe palpitation. Zhigancao Tang has been widely used for the treatment of over 70 diseases classified into 10 systems， especially the cardiovascular diseases， in traditional Chinese medicine （TCM） and western medicine. As the “one” of “four in one”， Zhigancao Tang is composed of multiple Chinese herbs and its therapeutic effect is superior to the sum of its parts. It ameliorates the coronary heart disease by resisting inflammation， protecting against ischemia-reperfusion injury， adjusting the ion channels of myocardial cells， and participating in atrial remodeling and hematopoiesis. Its mechanism and clinical efficacy in the treatment of coronary heart disease have been verified by clinical and experimental studies. The utilization of the thought of "four in one" to analyze classical prescriptions enables the combination of prescriptions with syndromes， which is of great significance to the clinical application and modern development of classical prescriptions.

Paeonol regulates phenotypic conversion of macrophages via estrogen receptor-a / 中国药理学通报

Aim To study the effect of paeonol on macrophage phenotvpe conversion based on estrogen receptora (ERa).Methods The macrophage Ml polarization model was established by 100 jjig • L"' LPS and 20 pug • L_1 I FN-7.ELISA was used to examine the effects of paeonol on tumor necrosis factor-a ( TNF-cx ) , interleukin-1 £ ( 1L-1 £ ) , interleukin-10 (IL-10), superoxide dismutase (SOD) , and malondi- aldehyde ( MDA).Western blot was used to detect the expression of M1 phenotvpe markers iNOS, CD86 and M2 phenotvpe markers Arg-1 and CD 163 in macrophages.Further, the methods of blockers and shRNA interference were used to verify whether the effect of paeonol was mediated by ERa.Results ELISA results shower] that paeonol reduced the content of TNF-a, IL- lp and MDA, and increased the content of IL-10 and SOD.Western blot results showed that paeonol reduced the expression of iNOS and CD86 proteins in model group, and increased the expression of Arg-1 and CD163 proteins.Both ERa selective blocker MPP and ERa shRNA reduced the efficacy of paeonol, while ERp selective blocker PHTPP had no significant effect on paeonol.Conclusion Paeonol can induce the transformation of macrophages into M2 type by ERa and alleviate the progression of atherosclerosis.

Senescent Mesenchymal Stem Cells Contribute to Progression of Myelodysplastic Syndromes-Review / 中国实验血液学杂志

Myelodysplastic syndromes (MDS) comprise a group of malignant hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis. The risk of transformation to acute myeloid leukemia (AML) is increasing. The initiating event in HSC of MDS leads to a growth advantage and subsequent clonal expansion, that is still poorly understood. Accumulating data indicate that the mesenchymal stem cells(MSCs) in MDS model display aberrant characteristics contributing to disease initiation and transformation into AML. MSC derived from MDS displayed the alteration in genetics, epigenetics and gene expression, which contribute to altered morphology, impaired proliferative and differentiation capacity and perturbed cytokine secretions, thus destroy in their ability to support normal hematopoiesis and contribute to malignant progression. A number of promising agents that target the interactions of the MDS clone with MSC are currently investigated in various phases of clinical trial, that might ultimately result in novel therapeutic strategies, targeting niche cells to attenuate leukemic progression. In this article, the current status of MDS treatment, the characteristics of MDS-MSC senescence and phenotypes, the changes of hematopoietic function sapported by senescent MDS-MSC, the significane of MDS-MSC in MDS prognosis and the MDS-MSC as potential target for treatment of MDS are summarized.

An investigation on the prevalence of chronic obstructive pulmonary disease and its influencing factors among residents in Yongjia County / 预防医学

Objective In order to explore the prevalence of chronic obstructive pulmonary disease (COPD)among residents aged over 40 in Yongjia County,and to provide basic data for the prevention and control strategies and measures of chronic obstructive pulmonary disease.Methods Residents were investigated by questionnaire investigation,body measurements, and pulmonary function tests.Questionnaire survey was including demographic information,chronic obstructive pulmonary disease knowledge awareness,personal and family history of the disease,respiratory symptoms,case management of respiratory diseases,risk factors.Body measurements were including height,body weight,waist circumference,blood pressure and heart rate.Pulmonary function tests was including one second forced expiratory volume (FEV1 ),forced expiratory volume (FEV6 ) and forced vital capacity (FVC ).Results A total of 585 residents were investigated, including 85 patients with chronic obstructive pulmonary disease,and the prevalence rate of 1 4. 53%.Male chronic obstructive pulmonary morbidity was higher than female (χ2 =44. 29,P=0. 001 ),and with age increased,the prevalence rate increased (χ2 =1 9. 56,P<0. 001 ).Single factor analysis showed that the main risk factors were male,age ≥40, often cough /expectoration,smoking,occupational exposure history.Multivariate logistic regression analysis showed that male (OR=1 . 962,95%CI:1 . 025 -3. 757),expectoration (OR=2. 346,95%CI:1 . 1 48 -4. 794)and age (in the age group of 50:OR=2. 561 ,95%CI:1 . 221 -5. 372;age≥60(OR=7. 438,95%CI:3. 601 -1 5. 361 )were the risk factors of chronic obstructive pulmonary disease (COPD).Conclusion Chronic obstructive pneumonia has become a public health problem that affects the health of the residents.We should take effective preventive measures against the risk factors.

The relevance between quantitative and type of chromosomal abnormality and leukemia transformation in myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate leukemia transformation rate in myelodysplastic syndrome (MDS) and the relationship with quantitative and type of chromosomal abnormality.</p><p><b>METHODS</b>This study retrospectively analyzed and rediagnosed 138 MDS patients with complete data, investigated the rate and time of leukemia transformation, and analyzed characteristics of chromosome karyotype of de novo patients.</p><p><b>RESULTS</b>29 (21.01%) of 138 patients transformed into leukemia, the rate and the median time of leukemia transformation were 21.01% and 8 (3-24) months, respectively, among which, the rate of leukemia transformation in normal karyotype, abnormal karyotype analysis of ≤5 mitotic cells, and >5 mitotic cells in split phase groups were 6.2%, 23.8% and 38.5%, respectively, and median time of which were 17(13-22), 13(5-23), and 7(3-10) months, respectively. Increased trend of leukemia conversion rate along with increased quantity of chromosomal abnormality was observed (χ²=14.185, P＜0.01). Leukemia transformation time negatively correlated with quantity grade of abnormal karyotype (r=-0.631, P<0.01), The leukemia transformation rates in monosomy 7/del 7q, trisomy 8, trisomy 11, complex karyotype and normal karyotype groups were 65.0%, 50.0%, 30.8% and 28.6%, being significantly different (χ²=21.555, P<0.01). Leukemia transformation rate of complex karyotype and monosomy 7/del 7 q was slightly higher than of trisomy 8 and trisomy 11, but both of them were significantly higher than of normal karyotype (χ²=8.054, P=0.005). There were no leukemia transformation cases in del 5q, del 20q, monosomy Y, and trisomy 21 group.</p><p><b>CONCLUSION</b>With or without abnormal chromosome karyotype, quantity and types of abnormal karyotype had important clinical value to predict leukemia transformation in patients with MDS.</p>

In-hospital death of acute myocardial infarction patients and the influencing factors: A retrospective analysis / 第二军医大学学报

Objective To investigate the causes of in-hospital death of acute myocardial infarction(AMI) patients and to analyze the independent predictors of the death. Methods We retrospectively analyzed the clinical data of 1 319 AMI patients who were treated from December 2006 to January 2012 in our hospital, and the data included the general condition, medical history and family history, admission examination, clinical diagnosis, complication, treatment and in-hospital death and the reasons. Results (l)The in-hospital mortality rate of AMI patients was 7. 4% in the past five years in our hospital, with the rate of female being significantly higher than that of males (13. 2% vs 5. 9%,P = 0. 000), with those who received no operation being significant higher than those received (31. 4% vs 3. 4%,P = 0. 000), and with those received emergent operation being significantly higher than those received selective operation (5. 0% vs 2. 2%,P = 0. 008). The incidence rate of cardiogenic shock was 10. 6% in patients with AMI, and they had an in-hospital death rate of 47. 1%, with those received no operation being significantly higher than those received emergent and selective operation (80. 4% vs 34. 5%, 17. 6%, P = 0. 000). (2)The in-hospital death (controlling gender) was positively associated with age, urea acid, blood urea nitrogen, creatinine, cystatin C, glucose, white blood cell, peak concentration of troponin, B-type natriuretic peptide (BNP), presence of arrhythmia, cardiogenic shock, Killip 3-4 group, placement of intraaortic balloon pump (IABP), and receiving no operation, and was negatively associated with red blood cell, hemoglobin, hematocrit, and use of drugs. (3)Independent risk factors of in-hospital death of AMI patients include d: female sex, older age, high level of blood urea nitrogen, glucose, peak concentration of troponin and BNP, presence of arrhythmia, cardiogenic shoe k, Killip 3-4 group, receiving no operation, placement of IABP, and receiving no drugs. Conclusion Prompt reperfusion is the best treatment choice for AMI patients, especially for those presenting with cardiogenic shock. More emphasis should be given to predictors of in-hospital mortality, such as age, blood urea nitrogen, glucose, peak concentration of troponin and BNP; also cystatin C should be examined for more patients with AMI in clinic.

Protective effect of Rhodiola extract against cisplatin-induced damage to TM4 sertoli cells in mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the preventive effect of Rhodiola extract on cisplatin (cDDP)-induced testicular toxicity in mouse TM4 Sertoli cell line and its possible mechanism in vitro.</p><p><b>METHODS</b>We treated mouse TM4 Sertoli cells with Rhodiola extract and/or cDDP. Then we detected the proliferation of the TM4 cells by MTT assay, observed their morphological changes, and determined the contents of malondialdehyde (MDA), superoxide dismutase (T-SOD) and glutathione (GSH) in the cells.</p><p><b>RESULTS</b>MTT assay showed that Rhodiola extract at the concentration of 0.0125-2.5 mg/L significantly inhibited the cDDP-induced decrease in the proliferation of the TM4 cells (P < 0.01) and improved their morphological changes. Anti-oxidation test exhibited a dramatically increased level of MDA in the TM4 cells treated with cDDP at 0.0147 g/L as compared with the normal control cells ([3.63 +/- 0.02] vs [2.15 +/- 0.02] nmol/mg prot, P < 0.01) and decreased levels of T-SOD ([6.57 +/- 0.05] vs [10.86 +/- 0.02] U/mg prot, P < 0.01) and GSH ([1.42 +/- 0.06] vs [2.59 +/- 0.05] mg/g prot, P < 0.01). Rhodiola extract at 0.1 mg/L significantly reduced the MDA content ([1.94 +/- 0.00] nmol/mg prot, P < 0.01) and the activity of T-SOD ([8.50 +/- 0.02] U/mg prot, P < 0.01) and GSH ([2.41 +/- 0.04] mg/g prot, P < 0.01) in the TM4 cells treated with cDDP.</p><p><b>CONCLUSION</b>Rhodiola extract can significantly inhibit cDDP-induced damage to TM4 cells in mice, which may be associated with its antioxidant activity.</p>

Correlation of laboratory indexes with prognosis in patients with myelodysplastic syndrome / 中国实验血液学杂志

The myelodysplastic syndrome (MDS) is a group of hematopoietic stem cell-clonal disease. The International Prognostic Scoring System (IPSS) is mainly used for its prognostic classification, but still remains some unrepeatable results in the same group of patients with MDS. This study was aimed to compare the levels of peripheral blood mean corpuscular volume (MCV), serum lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), ferroprotein (SF), Vit B12 in patients with MDS classified by IPSS and to explore the relationship between the prognosis and laboratory indexes above mentioned in MDS patients. 116 patients with MDS were divided into 4 group: low-risk, intermediate risk-I, intermediate risk-II and high-risk according to IPSS. The index of MCV, serum LDH, β2-MG, SF and Vit B12 in MDS patients prior treatment and in normal control group were detected. Data with normal group and each groups of MDS were compared. The results showed that the levels of MCV, LDH, β2-MG, SF were Vit B12 in patients with MDS were significantly higher than those in normal control group (P < 0.05). There were significant differences of serum LDH among the 4 groups of MDS (P < 0.05), and the levels of serum LDH increased in turn: low-risk, intermediate risk I, intermediate risk II and high-risk. Serum β2-MG level in the high-risk group was significantly higher than that in the groups of low risk, intermediate risk I and intermediate risk II (P < 0.05), the difference among the latter three groups was not statistically significant (P > 0.05). There were no significant differences in MCV, SF and Vit B12 levels of all groups compared with each other. It is concluded that the level of serum LDH and β2-MG seems to have a certain correlation with the progress and prognosis of the MDS, which may be useful for predicting the prognosis of the MDS besides IPSS scoring system.

Nuclear factor κB and IKB expression and calcium deposition of atherosclerotic plaques in apolipoprotein E and low density lipoprotein receptor knockout mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the histopathological features, nuclear factor-κB (NFκB) and IKB expressions as well as calcium deposition of atherosclerosis plaques (AS) in apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) knockout mice (ApoE(-/-), LDLR(-/-)fed high-fat diet.</p><p><b>METHODS</b>Eight C57BL/6J mice fed with normal diet were used as control, 32 ApoE(-/-) mice and LDLR(-/-) mice were divided into normal diet and high-fat diet groups (n = 8 each). After 4 months, aorta was collected for morphologic (HE, Oil Red O, Von Kossa) and immunohistochemistry (nuclear factor-κB, IKB, macrophage surface molecule-3, α-smooth action protein) analysis.</p><p><b>RESULTS</b>Degree of AS in ApoE(-/-) and LDLR(-/-) mice fed with high-fat diet were significantly severer than those fed with normal diet and AS was more significant in ApoE(-/-) mice than in LDLR(-/-) mice. NFκB and IKB expressions in high-fat diet group were significantly higher than the normal diet group (P < 0.05). Double-labeling of NFκB revealed dominant expression in smooth muscle cells. Calcium deposition was significantly more in ApoE(-/-) mice fed with high-fat diet than mice fed with normal diet (P < 0.05) and was similar in LDLR(-/-) mice fed with high and normal diet (P > 0.05).</p><p><b>CONCLUSION</b>High-fat diet contributes to the formation of AS plagues in ApoE(-/-) and LDLR(-/-) mice joined by upregulated NFκB and IKB expressions and calcium deposition.</p>

Construction and transfection experiment of a goose circovirus infectious clone / 病毒学报

A pair of primers with BamH I restriction site were designed to amplify the complete genome of goose circovirus. Two copies of the genome were ligated in tandem and cloned into pGEM-T Easy vector to construct an infectious clone named as pGEMT-2GoCV. The pGEMT-2GoCV linearized with EcoR I was transfected to negative embryos and gosling with Lipfectamine. PCR detection verified the proliferation of GoCV in geese. Some sera of the embryo transfected group were detected to be positive at 2 and 4 weeks after hatching and one bursa was detected to be positive at 4 weeks. Some sera of the gosling transfected group were also detected to be positive at 2 weeks after transfection. Furthermore, the mark in the PCR products were identified by BamH I digestion and the GoCV in positive tissue and sera were quantitated by Real-time PCR. The results showed that the virus load in positive bursa was 1.57 x 10(6) copies/mg, the virus load in positive sera were 3.52 x 10(4)-5.92 x 10(5) copies/microL. In conclusion, the infectious DNA clone constructed with two copies of full-length GoCV genome in tandem can transfect embryo and gosling and propagate the marked goose circovirus.