[Impacts of Climate Change and Human Activities on NDVI Change in Eastern Coastal Areas of China].

Based on the datasets of normalized difference vegetation index (NDVI), temperature, precipitation, and solar radiation and the methods of trend, partial correlation, and residual analyses, this study explored the spatiotemporal variation in NDVI and its response to climate change from 1982 to 2019 in eastern coastal areas of China. Then, the effects of climate change and non-climatic factors (e.g., human activities) on NDVI trends were analyzed. The results showed that:① the NDVI trend varied greatly in different regions, stages, and seasons. On average, the growing season NDVI increased faster during 1982-2000 (stage I) than that during 2001-2019 (stage Ⅱ) in the study area. Moreover, NDVI in spring showed a more rapid increase than that in other seasons in both stages. ② For a given stage, the relationships between NDVI and each climatic factor varied in different seasons. For a given season, the major climatic factors associated with NDVI change were different between the two stages. The relationships between NDVI and each climatic factor showed great spatial differences in the study period. In general, the increase in growing season NDVI in the study area from 1982 to 2019 was closely related to the rapid warming. The increase in precipitation and solar radiation in stage Ⅱ also played a positive role. ③ In the past 38 years, climate change played a greater role in the change in growing season NDVI than non-climatic factors, including human activities. Whereas non-climatic factors dominated the increase in growing season NDVI during stage I, climate change played a major role during stage Ⅱ. We suggest that more attention should be paid to the impacts of various factors on vegetation cover variation during different periods to promote the understanding of terrestrial ecosystem changes.

Study on clinical nursing pathway to promote the effective implementation of sepsis bundle in septic shock.

BACKGROUND: There is still a certain gap between the effective implementation and requirements of sepsis bundle. Our aim is to establish the clinical nursing pathway of the cluster treatment of septic shock in the Intensive Care Unit and promote effective implementation of the cluster treatment of septic shock. METHODS: By means of evidence-based method, quality control index requirements and on-site investigation, the implementation process of clinical nursing pathway of the cluster treatment within 6 h of diagnosis of septic shock was established. RESULTS: After the implementation of clinical nursing pathway, the completion rate of septic shock cluster treatment was 81.4% (66.4%) in 1 h, 89.4% (77.0%) in 3 h, 95.5% (82.3%) in 6 h (P < 0.05), which was significantly improved in the experimental group compared with the control group. CONCLUSIONS: The clinical nursing pathway of septic shock cluster treatment is guided by evidence-based nursing, which emphasizes standardization and standardization of septic shock cluster treatment nursing under the guidance of the guideline, and can promote the effective implementation of septic shock cluster treatment, significantly improve efficiency of septic shock treatment and the quality of medical care.

Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer: A meta-analysis.

OBJECTIVES: This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC). MATERIALS AND METHODS: Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3. RESULTS: Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3+, CD4+, CD4+/CD8+, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04). CONCLUSIONS: It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.

Pathways involved in pony body size development.

BACKGROUND: The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages. RESULTS: We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCß2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P < 0.05) in vitro. Transduction of ATDC5 cells with a GHR-RNAi lentiviral vector decreased the expression of the GHR pathway components (P < 0.05). Additionally, the expression of the IGF-1 gene in the liver was lower in Debao ponies than in Mongolian horses at the juvenile and adult stages. Detection of plasma hormone concentrations showed that Debao ponies expressed higher levels of IGF-1 as juveniles and higher levels of GH as adults than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses. CONCLUSION: Our work provides insights into the genetic regulation of short stature growth in mammals and can provide useful information for the development of therapeutic strategies for small size.

Distribution and prognostic impact of M1 macrophage on esophageal squamous cell carcinoma.

Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient's lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC.

Tumor-associated macrophage polarization promotes the progression of esophageal carcinoma.

The immune response facilitated by tumor-associated macrophages is a vital determinant of tumor progression. We identified differentially expressed genes between various macrophage phenotypes in the Gene Expression Omnibus, and used Kaplan-Meier Plotter to determine which of them altered the prognosis of esophageal carcinoma patients. Fibrinogen-like protein 2 (FGL2), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher FGL2 expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that FGL2 expression correlated positively with the levels of immune markers of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in esophageal carcinoma samples. Correlation analyses in cBioPortal revealed that the mRNA levels of FGL2 correlated strongly with those of interleukin 10, matrix metalloproteinase 9, C-C motif chemokine ligand 5, T-cell immunoglobulin mucin 3, interleukin 13, vascular cell adhesion molecule 1, macrophage colony-stimulating factor and fibroblast growth factor 7 in esophageal carcinoma tissues. The same cytokines were upregulated when esophageal squamous cell carcinoma cells were co-cultured with M2-like tumor-associated macrophages. Thus, by secreting FGL2, M2-like tumor-associated macrophages may create an immunosuppressive tumor microenvironment that induces the occurrence and progression of esophageal carcinoma.

Efficacy of Adherence-Enhancing Interventions for Immunosuppressive Therapy in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

BACKGROUND: Immunosuppressant non-adherence is a widespread problem among solid organ recipients. With the newly published clinical trials, the randomized controlled trials (RCTs) based systematic review of adherence-enhancing interventions on immunosuppressant adherence in solid organ recipients has not been completed. In this systematic review and meta-analysis, we compared the efficacy of adherence-enhancing interventions versus routine intervention, as performed with RCTs, on immunosuppressant adherence in solid organ transplantation recipients. METHODS: PubMed, Embase, Cochrane Library, CINAHL full text, and PsycINFO were searched from database inception to December 2019. This review was conducted following the PRISMA's reporting guidelines and according to the principles recommended by Cochrane Handbook for Systematic Review. RESULTS: The search yielded 10,479 articles. A total of 27 articles (26 studies) with 715 participants were included in our analysis. Results from the meta-analysis revealed that as compared with that of the routine intervention group, the rates of overall adherence, dosing adherence, and timing adherence were significantly increased within the adherence-enhancing intervention group, with the pooled risk ratio (RR) of overall adherence = 1.17, [95% confidence interval (CI): 1.07 to 1.28; p = 0.0006]; RR of dosing adherence = 1.21 (95% CI: 1.08 to 1.36, p = 0.001); RR of timing adherence = 1.16 (95% CI: 1.03 to 1.29, p = 0.01). There was a significantly increased adherence score in the adherence-enhancing intervention group; however, no statistical significance on the immunosuppressant blood concentration was found between the two study groups. Results obtained from a subgroup analysis shown interventions led by a multidisciplinary team, both the assessment time at 6 months and 12 months demonstrated a significantly increased adherence rate in the intervention group compared with the control group. CONCLUSIONS: The findings of this report indicate that clinicians (doctors and nurses) should maintain a long-term intervention protocol to ensure immunosuppressant adherence within solid organ transplant recipients. To accomplish this goal, we recommend a multidisciplinary team-led, comprehensive intervention approach combined with mobile health monitoring for the administration of an effective immunosuppressive therapy regimen.

Application of Low Tube Voltage, Low-concentration Contrast Agent Using a 320-row CT in Coronary CT Angiography: Evaluation of Image Quality, Radiation Dose and Iodine Intake.

The effect of low voltage and low concentration contrast agent on image quality of coronary CT angiography, radiation dose and iodine intake was evaluated. A total of 121 patients with body mass index (BMI) <26 kg/m2 and heart rate (HR) <70 beats/min were randomly divided into four groups: group A (n=31, 80 kVp, 270 mgI/mL); group B (n=33, 100 kVp, 270 mgI/mL); group C (n=30, 100 kVp, 320 mgI/mL); group D (n=27, 100 kVp, 400 mgI/mL). The automatic current modulation system and the iterative algorithm for reconstruction were adopted in each group. The CT values and SD values of the aortic root (AR), subcutaneous fat, left coronary artery opening (LCA), and right coronary artery opening (RCA) were measured in all groups, the signal-to-noise ratio (SNR) and contrast noise ratio (CNR) were calculated, and effective radiation dose and iodine intake were recorded. The subjective assessment for image quality was performed by two physicians using a 4-point scale. The results were compared using the one-way ANOVA and rank sum tests. The image quality of the four groups met the clinical diagnostic requirements. The CT values of AR in groups A, B, C, and D were 537.6±71.4, 447.2±81.9, 445.2±64.9 and 518.5±94.9 Hu, respectively, with no significant difference between group A and group D, or between group B and group C, while CT values in groups B and C were significantly lower than those in groups A and D (P<0.05). In groups A, B, C, and D, the LCA SNR values were 22.7±9.1, 23.3±9.1, 23.3±7.7 and 26.6±8.9, and the RCA CNR values were 26.9±9.8, 28.5±11.4, 27.7±8.8 and 32.1±10.6, respectively. The AR visual scores in groups A, B, C and D were 3.8±0.2, 3.9±0.3, 3.9±0.3 and 4.0±0.3, respectively. There were no significant differences in SNR, CNR and visual score among the four groups (P>0.05). The radiation doses in groups A, B, C and D were 2.6±1.4, 3.6±1.8, 4.9±3.5 and 4.9±2.8 mSv, respectively. The radiation dose in group A was significantly less than that in the rest three groups (P<0.05). The iodine intakes in groups A, B, C and D were 14.9±1.5, 15.0±1.5, 17.7±2.0 and 18.1±2.5 g, respectively. There was no significant difference in the intake of iodine between groups C and D, or between groups A and B, while iodine intake in groups A and B were significantly reduced as compared with that in groups C and D (P<0.05). It was concluded that for patients with low BMI and controlled HR, compared to 100 kVp tube voltage combined with multiple concentration contrast agents, 80 kVp combined with 270 mgI/mL contrast agent is enough to ensure the quality of the images, and can reduce the radiation dose significantly, while reducing the amount of iodine intake notably, thus reducing the incidence of adverse reaction.

Bioinformatics-based screening of key genes for transformation of liver cirrhosis to hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. METHODS: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. RESULTS: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. CONCLUSION: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

Mechanistic Insight into the Chemiluminescent Decomposition of Cypridina Dioxetanone and the Chemiluminescent, Fluorescent Properties of the Light Emitter of Cypridina Bioluminescence.

Cypridina bioluminescence has been increasingly used in bioimaging, bioanalysis, and biomedicine, due to high quantum yield and high signal-to-noise ratio. However, there is still no consensus regarding different aspects of the chemiluminescent mechanism of this system, which impairs the development of new applications. Herein, we have used a theoretical DFT and TD-DFT approach to (i) determine the identity of the dioxetanone species responsible for efficient chemiexcitation and (ii) identify the bioluminescent emitter and determine if light-emission occurs from the fluorescent or chemiluminescent state. Our results demonstrate that upon oxygenation of the imidazopyrazinone scaffold, a dioxetanone with a neutral amide group and a cationic guanidinopropyl group is formed. This species is efficiently chemiexcited (with no obvious charge transfer step) to the corresponding oxyluciferin with a neutral amide and cationic guanidinopropyl groups. After the "dark" chemiluminescent state, this oxyluciferin species is converted into a bright blue-emitting fluorescent state.

The effects and mechanisms of a biosynthetic ginsenoside 3ß,12ß-Di-O-Glc-PPD on non-small cell lung cancer.

BACKGROUND: A biosynthetic ginsenoside, 3-O-ß-D-glucopyranosyl-12-O-ß-D-glucopyranosyl-dammar-24-ene-3ß, 12ß, 20S-triol (C3C12PPD), showed antitumor activity against many tumor cells in vitro, especially had better anti-lung cancer activity than Rg3 in vitro and in vivo. However, the effects and molecular mechanisms of C3C12PPD on non-small cell lung cancer (NSCLC) remain unclear. According to previous studies, we hypothesized ginsenoside C3C12PPD could inhibit the tumor growth of NSCLC by targeting proliferation, migration and angiogenesis. METHODS: A thiazolyl blue tetrazolium bromide assay (MTT) was performed to evaluate cell viability. Additionally, Transwell and tube formation assays were conducted to analyze cell migration and angiogenesis. The Lewis and A549 tumor xenograft experiments were also performed to investigate the effects of C3C12PPD on tumor growth in vivo, Western blotting and IHC assay were performed to analyze protein expression. RESULTS: C3C12PPD could effectively inhibit the proliferation and migration of lung cancer cells, and tube formation of EA.hy926 cell. Ginsenoside C3C12PPD suppressed Lewis and A549 tumor growth in vivo without obvious side effects on body weight and the hematology index. In addition, the Western blot analysis revealed that the effects of C3C12PPD on lung cancer were mediated by inhibiting Raf/MEK/ERK, AKT/mTOR and AKT/GSK-3ß/ß-Catenin signaling pathways. Finally, C3C12PPD could significantly inhibit the proliferation index and vessel number in Lewis xenograft tumors analyzed by IHC. CONCLUSION: The results of the present study suggest that ginsenoside C3C12PPD may serve as a potential therapeutic candidate compound against NSCLC.

[Detection methods of genome editing in plants].

The life science has entered a new chapter with the revolutionary implementation of the CRISPR/Cas9 genome editing technology in various living organisms. With the unique flexibility, feasibility and extendibility, the CRISPR/Cas9 technology greatly accelerates genetic engineering research, as well as plant molecular breeding. However, it has become a challenge to screen for and identify genome-edited plants at early stages in a rapid and high-throughput fashion, due to the massive number of plants produced from transformation process. In this review, we summarize the molecular methods developed in recent years to identify genome-edited plants. We compare their advantages and disadvantages, and the scope of application. In addition, we provide insights of the development trend of detection methods for plant genome editing. This review will serve as a reference for future genome editing research in plants.

Laser capture microdissection for detecting the expression of epithelial-mesenchymal transition-related genes in epithelial and spindle cells of paraffin-embedded formalin-fixed biphasic synovial sarcoma.

Synovial sarcoma (SS) is a mesenchymal malignant neoplasm showing characteristics of epithelial-mesenchymal biphasic differentiation. SS is of uncertain cellular origin; however, studies have suggested that SS originates from a somatic stem cell population. In this study, we aim to determine whether differential morphological features of the epithelial-mesenchymal transition (EMT) contributed to the tumourigenesis of SS invasion and metastasis. Twelve paraffin-embedded formalin-fixed tissue (FFPE) SS tissue specimens were obtained, and laser capture microdissection (LCM) with the ArcturusXT system and small chip method (SCM) were used to isolate and purify spindle and epithelial cells from SS specimens. The TRIzol method was used to extract RNA, and the mRNA levels of EMT-related genes in epithelial and spindle cells of SS specimens were measured using real-time fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results show that collection of about 2 × 104 cells from FFPE samples using LCM was sufficient for qRT-PCR, with an efficiency of 75%. Compared with LCM, 72.2% (13 of 18) RNA samples were successfully extracted using SCM to isolate cells from FFPE SS tissues. In the 16 samples (11 spindle cell samples and 5 epithelial cell samples), Snail mRNA was significantly upregulated in spindle cell areas compared with that in epithelial cell areas (P = .001). Expression levels of the epithelial marker E-cadherin and the mesenchymal marker N-cadherin were not significantly different between epithelial and spindle cell areas. In spindle cells of recurrent SS samples, the mRNA levels of E-cadherin, N-cadherin, Snail, and Slug were higher in primary SS samples than in recurrent samples. Taken together, our results indicated that in SS samples, Snail mRNA was upregulated in spindle cell areas compared with that in epithelial cell areas and that the expression of EMT-related genes was increased in primary SS. LCM could be used to isolate and purify RNA from FFPE samples.

HLA-DQB1*03 and DRB1*07 alleles increase the risk of cervical cancer among Uighur and Han women in Xinjiang, China.

AIM: To explore the association between the determinant factors including HLA-DQB1*03, DRB1-*07, -*13 and high-risk HPV infection, the cervical squamous cell carcinoma (CSCC) pathogenesis among Chinese Uighur and Han population. MATERIALS & METHODS: HLA alleles were genotyped by PCR sequence-specific primers. RESULTS: HPV16 infection rate was significantly higher among the Uighurs and Hans with CSCC as compared with healthy controls, respectively. HLA-DQB1*03 significantly increased among Uighurs with CSCC, while HLA-DRB1*07 significantly increased among Hans with CSCC. Similar tendencies were observed for DQB1*03 with HPV16-positive Uighurs CSCC and DRB1*07 with HPV16-positive Hans CSCC. CONCLUSION: This study suggests that HLA-DQB1*03 and DRB1*07 alleles may influence the immune response to HPV16 infection and increase the risk of CSCC among the Uighurs and Hans in China.

Genome-wide screening for genomic aberrations in Kazakh patients with esophageal squamous cell cancer by comparative genomic hybridization.

Multiple chromosome aberrations are responsible for tumorigenesis of esophagus squamous cell carcinoma (ESCC). To characterize genetic alterations by comparative genomic hybridization (CGH) and their relation to ESCC, We enrolled 54 members with ESCC from Kazakh's patients. We found that the deletions of 3p (P = 0.032), 17p (P = 0.004), 22q (P = 0.000) and gains of 5p (P = 0.000), 11q (P = 0.000) were significantly correlated with the location of tumors. Losses of 1p (P = 0.005), 3p (P = 0.006), 22q (P = 0.024) and gains of 3q (P = 0.043), 8q (P = 0.038), 18q (P = 0.046) were also found more frequently in patients with larger diameter disease. The loss of 19q (P = 0.005) and gains of l3q (P = 0.045), 18p (P = 0.018) were significantly correlated with pathologic grade. The gain of 7p (P = 0.009) and deletion of 19q (P = 0.018) were seen more frequently in patients with Grade III-IV tumors. Chromosome amplifications in ESCC at 1q (P = 0.008), 7p (P = 0.008), 8q (P = 0.018) and deletions at 3p (P = 0.021), 11q (P = 0.002), 17p (P = 0.012) were related to lymph node metastasis; the gains of 1q (P = 0.026) and 6q (P = 0.017) and the loss of 11q (P = 0.001) were significant in different isoforms of HPV infection. We identified some chromosomes in which the genes were related to the tumorgenesis of ESCC, which may be a theme for future investigation.

MicroRNA-34a functions as a tumor suppressor by directly targeting oncogenic PLCE1 in Kazakh esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the frequent malignant tumors with poor prognosis worldwide. Identifying the prognostic biomarkers and potential mechanisms of such tumors has attracted increasing interest in esophageal cancer biology. Our previous study showed that phospholipase C elipson 1 (PLCE1) expression is up-regulated and associated with disease progression in esophageal carcinoma. MicroRNAs (miRNAs) play vital roles in regulating its target gene expression. However, studies on miRNA-regulated PLCE1 expression and its cellular function are still very few. We found that miR-34a is significantly expressed lower in ESCC tissues. We further showed that PLCE1 is a direct functional target gene of miR-34a, and the functional roles of miR-34a in ESCC cell lines in vitro were also determined through gain- and loss-of-function analyses. Results revealed that miR-34a functions as a tumor suppressor by inhibiting the proliferation, migration, and EMT phenotype, as well as promoting apoptosis of ESCC cell lines. Moreover, PLCE1 is overexpressed in ESCC tumors and promotes tumorigenicity in vivo and vitro. PLCE1 expression is negatively correlated with miR-34a profiles in ESCC tissues. Our data suggest that miR-34a exerts its anti-cancer function by suppressing PLCE1. The newly identified miR-34a/PLCE1 axis partially illustrates the molecular mechanism of ESCC metastasis and represents a new candidate therapeutic target for ESCC treatment.

CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma.

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

The Association of MME microRNA Binding Site Polymorphism with the Risk of Late Onset Alzheimer's Disease in Northern Han Chinese.

BACKGROUND: Although ß-amyloid (Aß) degradation has been normally implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) through cellular biological studies, the genetic studies linking Aß degradation and LOAD are still scarce. Neprilysin (NEP), one of the most crucial Aß-degrading enzymes in AD, is the metalloendopeptidase which particularly participates in the monomeric Aß species degradation. MicroRNAs (miRNAs) exert post-transcriptional dysregulation and their target sequence on the 3' untranslated regions (3'UTR) may be regulated by single nucleotide polymorphisms (SNPs). OBJECTIVE: To investigate the potential risk of common locus within NEP gene (MME) with LOAD in Northern Han Chinese population. METHOD: We screened a locus (rs6665) in 3' UTR of NEP gene (MME) which sequence was specially regulated by miRNA-187, and further investigated its possible association with LOAD onset in a large case-control study (984 LOAD patients and 1354 healthy controls) in Northern Han Chinese. RESULTS: The distribution of rs6665 genotype (P=0.003) and allele A/C (P=0.001) showed significant difference between LOAD and controls (Odds Ratio (OR) =1.255, 95% Confidence Interval (CI) =1.102-1.429). After adjusting for age, gender and Apolipoprotein (ApoE) ε4 status, the minor C allele of rs6665 showed significant association with LOAD in all three genotypic models (Dominant: P=0.003, OR=1.291, 95%CI=1.092-1.526; Recessive: P=0.030, OR =1.425, 95%CI =1.035- 1.961; Additive: P=0.001, OR=1.249,95%CI=1.093-1.427). After stratifying by ApoE ε4 status, rs6665 polymorphism was found to elevate the LOAD risk in ApoE ε4 carriers (P=0.002, OR=1.846, 95%CI=1.264-2.697). CONCLUSION: Our study firstly confirmed the association of MME miRNA binding site polymorphism with the risk of LOAD. However, the association results warrant further validation.

High infiltration of CD68-tumor associated macrophages, predict poor prognosis in Kazakh esophageal cancer patients.

Tumor-associated macrophages (TAMs), the most important immune cells in tumor microenvironment, were reported to play a key role in cancer progression, but the correlation of TAMs and Kazakh esophageal squamous cell carcinoma (ESCC) was still not clear, so we sought to identify the function of TAMs in Kazakh ESCC clinicopathological and prognostic evaluation. CD68 as the TAMs marker, and immunohistochemistry (IHC) was used to quantify the TAMs infiltrated in tumor nest and stroma, the IHC staining was also used to evaluate the expression of MMP-9 in Kazakh ESCCs. The density of CD68-TAMs in ESCCs tumor nest and stromal, were significantly higher than those of CANs (P<0.05). The increasing number of CD68-positive TAMs in tumor nest and stromal were positively associated with tumors lymph node metastasis and clinical stage (P<0.05). The expression of MMP-9 in Kazakh ESCCs was higher than that of CAN tissues (P<0.05). Increased MMP-9 expression in ESCCs was significantly associated with lymph node metastasis and tumor clinical stage (P<0.05). Importantly, the number of CD68-positive TAMs in ESCCs was significantly correlated with the expression of MMP-9 (P<0.05). Furthermore, the survival analyses demonstrated that high-density of CD68-TAMs in tumor nest was positively related to the shorter overall survival time of patients (P<0.05). Increasing numbers of CD68-TAMs promote higher expression of MMP-9 and may play an important role in the occurrence and progression of Kazakh ESCCs, and which could be used as important prognostic markers for Kazakh ESCCs.

The increased number of tumor-associated macrophage is associated with overexpression of VEGF-C, plays an important role in Kazakh ESCC invasion and metastasis.

Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC. CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC.