Chromosome-level genome assembly of the Asian citrus psyllid, Diaphorina citri.

Diaphorina citri is a global citrus pest. As a vector insect, it can transmit the causative agents of citrus huanglongbing, causing irreversible losses to the citrus industry. The acquisition of genomic information can provide a molecular genetic basis for effective control of D. citri. Here, the DNBSEQ™ , Oxford Nanopore Technologies, and Hi-C technologies are applied to generate a high-quality chromosome-level genome of D. citri. The genome size of D. citri was 523.78 Mb with a scaffold N50 of 47.05 Mb distributed on 13 chromosomes. A total of 250.64 Mb (47.85%) repeat sequences and 24 048 protein-coding genes were predicted. Genome resequencing of female and male individuals indicated that the sex chromosome system of D. citri is XO. Phylogenetic analysis demonstrated that D. citri and Pachypsylla venusta, which separated from their most recent common ancestor about 336.62 million years ago, were the most closely related. Additionally, we identified genes potentially involved in detoxification metabolism, pathogen transmission, and honeydew secretion for further investigation. The high-quality genome provides an important reference for developing effective management strategies of D. citri.

Effects of Candidatus Liberibacter asiaticus infection on metagenome of Diaphorina citri gut endosymbiont.

Asian citrus psyllid (Diaphorina citri, D. citri) is the important vector of "Candidatus Liberibacter asiaticus" (CLas), associated with Huanglongbing, the most devastating citrus disease worldwide. CLas can affect endosymbiont abundance of D. citri. Here, we generated the high-quality gut endosymbiont metagenomes of Diaphorina citri on the condition of CLas infected and uninfected. The dataset comprised 6616.74 M and 6586.04 M raw reads, on overage, from CLas uninfected and infected psyllid strains, respectively. Taxonomic analysis revealed that a total of 1046 species were annotated with 10 Archaea, 733 Bacteria, 234 Eukaryota, and 69 Viruses. 80 unique genera in CLas infected D. citri were identified. DIAMOND software was used for complement function research against various functional databases, including Nr, KEGG, eggNOG, and CAZy, which annotated 84543 protein-coding genes. These datasets provided an avenue for further study of the interaction mechanism between CLas and D. citri.

Anti-apoptotic effect of adrenomedullin gene delivery on Leydig cells by suppressing TGF-ß1 via the Hippo signaling pathway.

This study aims to establish whether adrenomedullin (ADM) is capable to restore the steroidogenic functions of Leydig cells by suppressing transforming growth factor-ß1 (TGF-ß1) through Hippo signaling. Primary Leydig cells were treated with lipopolysaccharide (LPS), an adeno-associated virus vector that expressed ADM (Ad-ADM) or sh-RNA of TGF-ß1 (Ad-sh-TGF-ß1). The cell viability and medium concentrations of testosterone were detected. Gene expression and protein levels were determined for steroidogenic enzymes, TGF-ß1, RhoA, YAP, TAZ and TEAD1. The role of Ad-ADM in the regulation of TGF-ß1 promoter was confirmed by ChIP and Co-IP. Similar to Ad-sh-TGF-ß1, Ad-ADM mitigated the decline in the number of Leydig cells and plasma concentrations of testosterone by restoring the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD. Similar to Ad-sh-TGF-ß1, Ad-ADM not only inhibited the LPS-induced cytotoxicity and cell apoptosis but also restored the gene and protein levels of SF-1, LRH1, NUR77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD, along with the medium concentrations of testosterone in LPS-induced Leydig cells. Like Ad-sh-TGF-ß1, Ad-ADM improved LPS-induced TGF-ß1 expression. In addition, Ad-ADM suppressed RhoA activation, enhanced the phosphorylation of YAP and TAZ, reduced the expression of TEAD1 which interacted with HDAC5 and then bound to TGF-ß1 gene promoter in LPS-exposed Leydig cells. It is thus suspected that ADM can exert anti-apoptotic effect to restore the steroidogenic functions of Leydig cells by suppressing TGF-ß1 through Hippo signaling.

Local adrenomedullin gene delivery inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo.

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)-induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS-treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad-ADM, an adeno-associated virus vector that expressed ADM. Then, rat testes were collected for 3ß-hydroxysteroid dehydrogenase (3ß-HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor-1 (SF-1), liver receptor homologue-1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3ß-HSD, cytochrome P450 17α-hydroxylase/17, 20 lyase (CYP17) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF-1, LRH1, Nur77, StAR, P450scc, 3ß-HSD, CYP17 and 17ß-HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo.

A Transcriptomic and Proteomic Analysis of the Diaphorina citri Salivary Glands Reveals Genes Responding to Candidatus Liberibacter asiaticus.

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the principal vector of the Candidatus Liberibacter asiaticus (CLas) bacterium that causes Huanglongbing (HLB) disease. The D. citri salivary glands (SG) is an important barrier to the transmission of CLas. Despite its importance, the transcriptome and proteome of SG defense against CLas are unstudied in D. citri. In the present study, we generated a comparative transcriptome dataset of the SG in infected and uninfected D. citri using an Illumina RNA-Seq technology. We obtained 407 differentially expressed genes (DEGs), including 159 upregulated DEGs and 248 downregulated DEGs. Functional categories showed that many DEGs were associated with the ribosome, the insecticide resistance, the immune response and the digestion in comparison with CLas-infected SG and CLas-free SG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases confirmed that metabolism and immunity were important functions in the SG. Among the DEGs, 68 genes (35 upregulated and 33 downregulated) encoding putative-secreted proteins were obtained with a signal peptide, suggesting that these genes may play important roles in CLas infection. A total of 673 SG proteins were identified in uninfected D. citri by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis, and 30 DEGs (15 upregulated and 15 downregulated) were found using the local tBLASTP programs. Among the 30 DEGs, many DEGs mainly involved in the metabolism and cellular processes pathways. This study provides basic transcriptome and proteome information for the SG in D. citri, and helps illuminate the molecular interactions between CLas and D. citri.

KDM5C Represses FASN-Mediated Lipid Metabolism to Exert Tumor Suppressor Activity in Intrahepatic Cholangiocarcinoma.

Background: KDM5C is a histone H3K4-specific demethylase, which has multiple biological functions during development and disease. However, the role of KDM5C in intrahepatic cholangiocarcinoma (ICC) remains unknown. Methods: Expression levels of KDM5C in ICC patients were determined by qRT-PCR, western blotting and immunohistochemical assay. The functions of KDM5C in cell proliferation and invasion were determined in human ICC cells and mouse xenograft model using KDM5C overexpression and knockdown strategies in vivo. RNA-seq analysis was applied to investigate the transcriptional program of KDM5C. In addition, ChIP-qPCR was used to determine the regulation of FASN by KDM5C. Results: Here, we show that KDM5C was downregulated in human ICC, where its diminished expression was associated with poor prognosis. ICC cell proliferation and invasion were inhibited by KDM5C overexpression. Moreover, KDM5C suppressed ICC proliferation and metastasis in vivo. RNA-sequencing showed that KDM5C inhibits key signal pathways of cell proliferation, cell invasion and fatty acid metabolism. ChIP-qPCR revealed that overexpression of KDM5C led to the reduction of H3K4me3 on the promoter and the corresponding downregulation of the expression of FASN, which represents the major target gene of KDM5C to mediate the proliferation and invasion of ICC cells. Conclusions: Our results revealed the role of KDM5C as a novel tumor suppressor in ICC largely by repressing FASN-mediated lipid acid metabolism and thus KDM5C may contribute to the pathogenesis of ICC.

Odorant binding protein 2 reduces imidacloprid susceptibility of Diaphorina citri.

The Asian citrus psyllid, Diaphorina citri, is the principal vector of Huanglongbing pathogen Candidatus Liberibacter asiaticus (CLas), which causes severe economic losses to citrus industry worldwide. Use of broad-spectrum insecticides to control D. citri has resulted in considerable resistance development. Specific chemosensory proteins such as odorant binding proteins (OBPs) are potentially involved in reduced insecticide susceptibility. However, functional data on the contribution of OBPs to reduced susceptibility of D. citri are unavailable. We found that DcitOBP2 was stably expressed in different developmental stages and highly expressed in the legs, head and cuticle of D. citri. Expression of DcitOBP2 was significantly induced by 12 to 48 h of imidacloprid exposure and ranged from a 1.34- to 2.44-fold increase. RNAi of DcitOBP2 increased the susceptibility of D. citri adults to imidacloprid. The purified recombinant protein of DcitOBP2 expressed in Escherichia coli showed strong in vitro binding activity (Kd = 62.39 nM) to imidacloprid using microscale thermophoresis technology (MST). DcitOBP2 also had strong binding ability to thiamethoxam and dinotefuran but it had no response to abamectin, fenpropathrin and chlorpyrifos. The results showed that DcitOBP2 can interact with several neonicotinoid insecticides. This suggests that DcitOBP2 is involved in the decreased susceptibility of D. citri to imidacloprid. Our data reveal a new function of insect OBPs as a buffering protein that helps insects survive insecticide exposure. Our investigation may also aid in the development of new methods for resistance management of D. citri.

Adrenomedullin alleviates the pyroptosis of Leydig cells by promoting autophagy via the ROS-AMPK-mTOR axis.

Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells exposed to lipopolysaccharide (LPS) by promoting autophagy. Primary rat Leydig cells were treated with various concentrations of LPS and ADM, together with or without N-acetyl-L-cysteine (NAC) or 3-methyladenine (3-MA). Cell proliferation was detected through CCK-8 and BrdU incorporation assays, and ROS level was measured with the DCFDA assay. Real-time PCR, western blot, immunofluorescence, transmission electron microscopy, TUNEL and flow cytometry were performed to examine ADM's effect on the pyroptosis, autophagy and steroidogenic enzymes of Leydig cells and AMPK/mTOR signalling. Like NAC, ADM dose-dependently reduced LPS-induced cytotoxicity and ROS overproduction. ADM also dose-dependently ameliorated LPS-induced pyroptosis by reversing the increased expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18, GSDMD, caspase-3, caspase-7, TUNEL-positive and PI and active caspase-1 double-stained positive rate, DNA fragmentation and LDH concentration, which could be rescued via co-incubation with 3-MA. ADM dose-dependently increased autophagy in LPS-induced Leydig cells, as confirmed by the increased expression of LC3-I/II, Beclin-1 and ATG-5; decreased expression of p62 and autophagosomes formation; and increased LC3-II/LC3-I ratio. However, co-treatment with 3-MA evidently decreased autophagy. Furthermore, ADM dose-dependently rescued the expression of steroidogenic enzymes, including StAR, P450scc, 3ß-HSD and CYP17, and testosterone production in LPS-induced Leydig cells. Like rapamycin, ADM dose-dependently enhanced AMPK phosphorylation but reduced mTOR phosphorylation in LPS-induced Leydig cells, which could be rescued via co-incubation with 3-MA. In addition, pyroptosis was further decreased, and autophagy was further promoted in LPS-induced Leydig cells upon co-treatment with ADM and rapamycin. ADM may protect the steroidogenic functions of Leydig cells against pyroptosis by activating autophagy via the ROS-AMPK-mTOR axis.

MicroRNA-486-5p targeting PTEN Protects Against Coronary Microembolization-Induced Cardiomyocyte Apoptosis in Rats by activating the PI3K/AKT pathway.

Coronary microembolization (CME) is responsible for a substantial fraction of microvascular obstruction (MVO), which are strongly associated with mortality and hospitalization for heart failure within 1 year after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). However, the effect of miRNA on cardiomyocyte apoptosis in a CME model has been less well-studied. miRNA sequencing analysis was performed to examine differentially expressed miRNAs induced by CME in rats. Phosphatase and tensin homologue (PTEN) 3 'RACE and dual-luciferase reporter assays were performed to confirm that PTEN is a direct target gene of miR-486-5p. miRNA-486-5p overexpression was established by injecting AAV into rats via the tail vein. The CME model was established by injecting microspheres into the left ventricle of rats. 6h after surgery, cardiac function, microinfarct area, and the apoptotic index were determined. RT-PCR was used to evaluate mRNA level and Western blotting was used to evaluate protein expression. miRNA sequencing data showed that there were 5 upregulated and 8 downregulated miRNAs, and the relative expression of miRNA-486-5p was significantly downregulated. PTEN 3'RACE and dual-luciferase reporter assays confirmed that miR-486-5p directly targets the rat PTEN gene. The expression of miR-486-5p gradually declined, however, the expression of PTEN mRNA rapidly increased at early time points after CME. Overexpression of miR-486-5p reduced cardiomyocyte apoptosis and improved cardiac function through inhibition of PTEN and activation of the PI3K/Akt pathway in rat CME models. Overexpression of miR-486-5p, which targets PTEN, protects against CME-induced cardiomyocyte apoptosis and improves cardiac function in rats by activating the PI3K/Akt pathway.

Comparative transcriptome analysis reveals differentially expressed genes in the Asian citrus psyllid (Diaphorina citri) upon heat shock.

Temperature is an important factor influencing insect distribution. In the tropical and subtropical regions, insects always suffer the extreme temperature. Therefore, appropriate molecular response to temperature change is crucial for their survival. To understand how Diaphorina citri responds to high temperature at the molecular level, we conducted a comparative analysis of the transcriptomes of D. citri under room temperature and 40 °C heat shock treatment. The RNA sequencing analysis identified a total of 451 differentially expressed genes upon heat stress, including 167 down-regulated genes and 284 up-regulated genes. Thermal stress mainly significantly induced the transcription of molecular chaperone, protein biosynthesis and oxidation resistance, including members of the heat shock protein families, ATPases, and detoxifying enzymes. This study provides a preliminary insight into the transcriptional response of D. citri to heat stress and provides a foundation for the future functional validation of genes involved in thermotolerance in this important insect pest in tropical and subtropical regions.

Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy.

BACKGROUND/AIMS: Microvascular obstruction (MVO), an undesirable complication of percutaneous coronary intervention, is independently associated with adverse left ventricle remodeling and poor prognosis after acute myocardial infarction. Hypoxia and oxidative stress major roles in the pathophysiology of MVO. Pim1 serves an important protective role in the ischemic myocardium, but the underlying mechanisms remain poorly defined. Autophagy in early hypoxia or during moderate oxidative stress has been demonstrated to protect the myocardium. In this study, we investigated the association between the protective effect of Pim1 and autophagy after hypoxia and oxidative stress. METHODS: Ventricular myocytes from neonatal rat heart (NRVMs) were isolated. NRVMs were exposed to hypoxia and H2O2. Rapamycin and 3-methyladenine (3-MA) were used as an activator and inhibitor of autophagy, respectively. pHBAd-Pim1 was transfected into NRVMs. We assessed cardiomyocyte apoptosis by Annexin V-FITC/PI flow cytometry. Autophagy was evaluated by mRFP-GFP-LC3 adenovirus infection by confocal microscopy. Western blotting was used to quantify apoptosis or autophagy protein (caspase-3, LC3, P62, AMPK, mTOR, ATG5) concentrations. RESULTS: Autophagy and apoptosis in NRVMs significantly increased and peaked at 3 h and 6 h, respectively, after exposure to hypoxia and H2O2. The mTOR inhibitor rapamycin induced autophagy and decreased cardiomyocyte apoptosis, but the autophagy inhibitor 3-MA decreased autophagy and increased apoptosis at 3 h after exposure to hypoxia and H2O2. Pim1 levels in NRVMs increased at 3 h and decreased gradually after exposure to hypoxia and H2O2. Pim1 overexpression enhanced autophagy and decreased apoptosis. Pim1-induced promotion of autophagy is partly the result of activation of the AMPK/mTOR/ATG5 pathway after exposure to hypoxia and H2O2. CONCLUSION: Our results revealed that Pim1 overexpression prevented NRVMs from apoptosis via upregulating autophagy after exposure to hypoxia and oxidative stress, partly through activation of the AMPK/mTOR/ATG5 autophagy pathway.

Relationship between the Proportion of Tumor Infiltrating Lymphocytes in Tumor Mass and Postoperative Recurrence of Prostate Carcinoma / 昆明医科大学学报

Objective To investigate the relationship between proportion of Tumor infiltrating lymphocytes (TILs) in the prostate tumor mass and postoperative recurrence of prostate carcinoma in order to offer the theoretic as well as experimental basis for the prevention of postoperative recurrence in the prostate carcinoma.Methods The proportion of CD3+, CD8+, CD3+CD4+, CD3+CD8+ TILs cells of 81 PCa specimens underwent Radical prostatectomy were analyzed. The proportion of CD3+CD8+TILs in patients with recurrence of PCa within3 years after surgery (group A), within 35 years (group B) and without recurrence after 5 years (group C) was compared. Results The proportion of CD3+CD8+TILs was significantly lower in group A than that of in group B and C (P＜0.05), meanwhile, the proportion of CD3+CD8+TILs were significantly higher in group C than that in group A and B (P＜0.05), while the proportion of CD3+, CD8+, CD3+CD4+ in three groups had no significant difference (P＞0.05). Conclusion The proportion of CD3+CD8+TILs presented in the PCa specimen mass is relative to the postoperative recurrence of prostate cancer, which might be a biomarker for the surveillance of postoperative recurrence of PCa.

Comparison of Multiple Chronic Obstructive Pulmonary Disease (COPD) Indices in Chinese COPD Patients / 결핵및호흡기질환

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a serious chronic condition with a global impact. Symptoms of COPD include progressive dyspnea, breathlessness, cough, and sputum production, which have a considerable impact on the lives of patients. In addition to the human cost of living with COPD and the resulting death, COPD entails a huge economic burden on the Chinese population, with patients spending up to one-third of the average family income on COPD management in some regions is clinically beneficial to adopt preventable measures via prudent COPD care utilization, monetary costs, and hospitalizations. METHODS: Toward this end, this study compared the relative effectiveness of six indices in predicting patient healthcare utilization, cost of care, and patient health outcome. The six assessment systems evaluated included the three multidimensional Body mass index, Obstruction, Dyspnea, Exercise capacity index, Dyspnea, Obstruction, Smoking, Exacerbation (DOSE) index, and COPD Assessment Test index, or the unidimensional measures that best predict the future of patient healthcare utilization, cost of care, and patient health outcome among Chinese COPD patients. RESULTS: Multiple linear regression models were created for each healthcare utilization, cost, and outcome including a single COPD index and the same group of demographic variables for each of the outcomes. CONCLUSION: We conclude that the DOSE index facilitates the prediction of patient healthcare utilization, disease expenditure, and negative clinical outcomes. Our study indicates that the DOSE index has a potential role beyond clinical predictions.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome complicated with central nervous system vasculitic-like presentation:a case report / 天津医药

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a serious adverse drug reaction, characterized with rash, fever, lymphadenectasis, eosinophilia and visceral involvement. This article describes the clinical case of a patient with renal insufficiency after receiving sensitizing drugs,which resulted in limb weakness and cognitive impairment of center nervous system characterized by vasculitis imaging and responded well to glucocorticoid treatment-DRESS syndrome.

Risk analysis of imported schistosomiasis in Shanghai City from 2005 to 2015 / 中国血吸虫病防治杂志

Objective To understand the risk situation of imported schistosomiasis and its main influencing factors in Shang-hai City from 2005 to 2015. Methods A retrospective survey was performed,and the database was established based on the da-ta collection of imported schistosomiasis,Oncomelania hupensis snail situation and mobile population in Shanghai City from 2005 to 2015. Results From 2005 to 2015,the mobile population in Shanghai City increased by 123.92％,which reached about 9816500,and 54.70％of them were located in the inner suburban districts. The accumulated areas with snails of 7.13 hm2 were found in 16 towns of 4 outer suburbs(excluding Chongming District). A total of 23 cases of imported schistosomiasis were found in Shanghai City,and the number of the imported schistosomiasis cases was on the downward trend(rs=-0.782,P=0.004). From 2005 to 2009,11 out of 13 imported schistosomiasis cases(84.62％)were distributed in the inner suburban dis-tricts where no O. hupensis snails were found at the same time. From 2010 to 2015,9 out of 10 imported schistosomiasis cases (90％)were distributed in the outer suburban districts where O. hupensis snails were found at the same time. Conclusion The number of imported schistosomiasis cases in Shanghai is on the downward trend. However,the threat of imported schistosomiasis to the prevention and control of schistosomiasis in Shanghai City should not be ignored.

Influence of metoprolol combined lisinopril on cardiac function and serological markers in patients with heart failure / 心血管康复医学杂志

Objective:To explore influence of metoprolol combined lisinopril on cardiac function and serological mark-ers in patients with chronic heart failure(CHF).Methods:A total of 120 CHF patients treated in our hospital from May 2014 to May 2016 were enrolled.They were randomly and equally divided into lisinopril group and combined treatment group(received metoprolol combined lisinopril),both groups were treated for six months.Therapeutic effect,incidence rate of adverse reactions,levels of cardiac function indexes,C reactive protein(CRP),tumor nec-rosis factor α(TNF-α),N terminal pro B type natriuretic peptide(NT-proBNP),cystatin C(CysC)and neutrophil gelatinase associated lipocalin(NGAL)before and after treatment were compared between two groups.Results:Compared with before treatment,after six-month treatment,there were significant reductions in left ventricular end-diastolic dimension(LVEDd),left ventricular end-systolic dimension(LVESd),levels of CRP,TNF-α,NT-proBNP,CysC and NGAL,and significant rise in left ventricular ejection fraction(LVEF)in both groups,P=0.001 all.Compared with lisinopril group after six-month treatment,there were significant rise in total effective rate(73.33% vs.90.00%),P=0.018,and LVEF[(44.91 ± 2.45)% vs.(48.82 ± 3.55)%],P=0.001;and sig-nificant reductions in LVEDd[(50.34 ± 3.11)mm vs.(45.92 ± 3.04)mm],LVESd[(41.34 ± 3.33)mm vs.(35.53 ± 2.34)mm],levels of CRP[(14.47 ± 2.77)ng/L vs.(10.32 ± 3.01)ng/L],TNF-α[(157.78 ± 43.21)ng/L vs.(110.22 ± 29.01)ng/L],NT-proBNP[(932.43 ± 46.45)pg/ml vs.(464.21 ± 39.78)pg/ml],CysC[(1.34 ± 0.36) mg/L vs.(0.97 ± 0.22)mg/L]and NGAL[(117.69 ± 16.51)μg/L vs.(75.58 ± 10.22)μg/L]in combined treat-ment group,P=0.001 all.No adverse drug reaction was found in two groups.Conclusion:Compared with alone lisi-nopril,metoprolol combined lisinopril can effectively improve cardiac function,inhibit inflammation,relieve body injury,improve cardiac structure and effectively improve prognosis more in CHF patients,which is worth extending.

Let-7 inhibits self-renewal of hepatocellular cancer stem-like cells through regulating the epithelial-mesenchymal transition and the Wnt signaling pathway.

BACKGROUND: Tumor suppressive let-7 miRNAs are universally down-regulated in human hepatocellular carcinoma (HCC) versus normal tissues; however, the roles and related molecular mechanisms of let-7 in HCC stem cells are poorly understood. METHODS: We examined the inhibitory effect of let-7 miRNAs on the proliferation of MHCC97-H and HCCLM3 hepatic cancer cells by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, which was further confirmed by apoptosis and cell cycle studies. The sphere-forming assay was used to study the effects of let-7a on stem like cells. Through western blot, immunofluorescence and the luciferase-reporter assay, we explored the activity of epithelial-mesenchymal transition (EMT) signaling factors in HCC cells. qRT-PCR was applied to detect miRNA expression levels in clinical tissues. RESULTS: Let-7a effectively repressed cell proliferation and viability, and in stem-like cells, also let-7a decreased the efficiency of sphere formation.in stem-like cells. The suppression of EMT signaling factors in HCC cells contributed to let-7's induced tumor viability repression and Wnt activation repression. Besides, Wnt1 is critical and essential for let-7a functions, and the rescue with recombinant Wnt1 agent abolished the suppressive roles of let-7a on hepatospheres. In clinical HCC and normal tissues, let-7a expression was inversely correlated with Wnt1 expression. CONCLUSIONS: Let-7 miRNAs, especially let-7a, will be a promising therapeutic strategy in the treatment of HCC through eliminating HCC stem cells, which could be achieved by their inhibitory effect on the Wnt signaling pathway.

[Hydro-chemical Characteristics and Quality Assessment of Surface Water in Gongga Mountain Region].

The concentrations of major ions (K+, Na+, Ca2+, Mg2+, CO32-, HCO3-, Cl-, and SO42-), heavy metals (Cu, Cd, Pb, and Zn), and nutrient elements (N and P) in surface water collected from Gongga Mountain region were analyzed to decipher their spatial distribution and assess the water quality. The descriptive statistics, Gibbs Figure, and triangular diagrams of anions and cations were employed, and single factor evaluation was conducted. The results showed that the average value of total dissolved solid (TDS) in Gongga Mountain region was 103.22 mg·L-1 indicating low salinity, and the hydro-chemical type was HCO3-Ca. For whole catchment, the major ion chemistry of river water was controlled by carbonate weathering, while the effect of atmospheric deposition was high in the eastern area. The overall concentrations of heavy metals and nutrient elements were low, and the eastern area had significantly higher concentrations than the west. The quality of surface water was good from the whole point of view, while that in the west was better than the east. It indicated that the spatial distribution was mainly controlled by natural factors, but the water of southeast slope had been affected by humans.

Application value of DOSE Index Scoring System in Chronic Obstructive Pulmonary Disease / 昆明医科大学学报

Objective To explore the application value of DOSE index score in the peitients with chronic obstructive pulmonary disease.Methods 122 cases of plateau COPD patients were followed up for 12 months,and we recorded and analyzed the patient's health and life.We also recorde FEV 1 and DOSE scores of the patients with COPD,and record the COPD risk events,including the number of respiratory failure and death,and the times of hospitalization,total such confinement,outpatient expenses,hospitalization expenses,mMRC,and scored in the number of exacerbations,etc.Results The DOSE index score was negatively correlated with FEV1％ pred (r=0.73,P ＜ 0.05) for 122 COPD patients,and were positively correlated with mMRC (r=085,P ＜ 0.01),the annual number of exacerbations (r=0.71,P ＜ 0.01),respiratory failure (r=0.65,P ＜ 0.01),heart failure (r=0.50,P ＜ 0.01),number of outpatient service (r=0.12,P＜0.01),hospitalization time (r=0.70,P＜0.01),the totalsuchconfinement (r=0.66,P＜0.01),outpatient expenses (r=0.13,P＞ 0.13),hospitalization expenses (r=0.65,P＜0.01).ROC curve was used to analyzed the cut-off point and curve area of COPD DOSE index.Conclusion The DOSE index is a simple COPD assessment tools,and is closely related to the prognosis of patients and health.

[Study of Pregnancy Exposure to PFOS on Reproductive Toxicities and Mechanism in Male Offspring Rats].

OBJECTIVE: To explore the effects of testosterone synthesis in adult leydig cell (ALC) of male rats exposed by perfluorooctane sulfonate (PFOS) during pregnancy. METHODS: At gestations 12 day, the pregnant rats were exposed to PFOS (5 mg/kg, PFOS group) or 0.5% Tween (control group) by gavage, once a day for 8 consecutive days. On postnatal day (PND) 70, several indexes of male offspring rats were measured including body mass, testicular coefficient, sperm count, serum testosterone concentration. The mRNA levels of ALC associated with testosterone synthesis were detected by real-time quantitative RT-PCR. RESULTS: The result showed that sperm count and serum testosterone concentration decreased in male offspring rats of PFOS group (P < 0.05), and body mass was significantly lower (P < 0.001). The expression of steroidogenic acute regulatory factor (Star), scavenger receptor class B type 1 (Scarb1), Cyp11a1 (coding gene of cytochrome P450 side chain cleavage) and Hsd17b3 (coding gene of 17ß-hydroxysteroid dehydrogenase) were down regulated (P < 0.05), no significant statistical difference was observed on the mRNA level of insulin-like growth factor-1 (Igf1) and insulin-like factor 3 (Insl3). CONCLUSION: Gestational exposure to PFOS can inhibit the mRNA levels associated with testosterone synthesis, and decrease the ability of testosterone synthesis in ALC of male offspring rats.