Correlation Analysis of Serum Lipopolysaccharide, Nuclear Factor Erythroid 2-Related Factor 2 and Haem Oxygenase 1 Levels and Cognitive Impairment in Patients with Obstructive Sleep Apnoea.

Objective: To investigate the correlation between the levels of serum lipopolysaccharide (LPS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cognitive impairment in patients with obstructive sleep apnoea (OSA). Methods: Serum LPS, Nrf2, HO-1 levels and cognitive impairment were measured using the Montreal Cognitive Assessment (MoCA) score in 56 patients in the "severe" group, 67 patients in the "mild-to-moderate" group and 100 healthy people in the "control" group. The differences in general conditions and serological indexes between the three groups were compared, the correlation between the MoCA scores and the serological indexes was explored and the independent predictors of the MoCA scores were analysed. Results: Serum LPS, Nrf2 and HO-1 levels were higher in the severe group than in the mild-to-moderate group and the control group (p < 0.05). A total of 71 patients with OSA had combined cognitive impairment, accounting for 57.7%, and the MoCA scores were lower in the severe group than in the mild-to-moderate group and the control group (p = 0.018). Serum LPS, Nrf2 and HO-1 levels were significantly higher in the severe group and mild-to-moderate group than in the control group (p < 0.05) and were negatively correlated with the MoCA scores. Lipopolysaccharide (p < 0.001) and HO-1 (p = 0.002) could be considered independent predictors of the MoCA score. Conclusion: Serum LPS and HO-1 levels are closely related to cognitive impairment in patients with OSA and have potential clinical value in the diagnosis.

Distribution characteristics of intestinal flora in patients with OSAHS and the relationship between different intestinal flora and sleep disorders, hypoxemia and obesity.

OBJECTIVE: To investigate the distribution characteristics of intestinal flora in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS) of different severities and the relationship between different intestinal flora and sleep structure disorder, hypoxemia and obesity. METHODS: A total of 25 healthy volunteers and 80 patients with OSAHS were enrolled in this study. The control group was healthy, and the experimental group comprised patients with OSAHS. The apnoea-hypopnea index (AHI), minimum saturation of peripheral oxygen (SpO2min), mean saturation of peripheral oxygen, body mass index, maximum apnoea time and other indicators were collected in clinical practice. The patients with OSAHS were divided into 20 mild and 42 moderate OSAHS cases, as well as 18 patients with severe OSAHS according to the AHI classification. Bioinformatics-related statistics were analysed using the QIIME2 software, and clinical data were analysed with the SPSS 22.0 software. RESULTS: The changes in microbial alpha diversity in the intestinal flora of patients with OSAHS showed that richness, diversity and evenness decreased, but the beta diversity did not change significantly. The Thermus Anoxybacillus, Anaerofustis, Blautia, Sediminibacterium, Ralstonia, Pelomonas, Ochrobactrum, Thermus Sediminibacterium, Ralstonia, Coccidia, Cyanobacteria, Anoxic bacilli and Anaerobes were negatively correlated with AHI (r = -0.38, -0.36, -0.35, -0.33, -0.31, -0.29, -0.22, -0.18) and positively correlated with SpO2min (r =0.38, 0.2, 0.25, 0.22, 0.24, 0.11, 0.23, 0.15). CONCLUSION: Some bacteria showed a significant correlation with clinical sleep monitoring data, which provides a possibility for the assessment of disease risk, but the mechanisms of their actions in the intestinal tract are not clear at present. Further research and observations are needed.

Knockdown of TFRC suppressed the progression of nasopharyngeal carcinoma by downregulating the PI3K/Akt/mTOR pathway.

BACKGROUND: The transferrin receptor (TfR) encoded by TFRC gene is the main cellular iron importer. TfR is highly expressed in many cancers and is expected to be a promising new target for cancer therapy; however, its role in nasopharyngeal carcinoma (NPC) remains unknown. METHODS: The TfR levels were investigated in NPC tissues and cell lines using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. Knockdown of TFRC using two siRNA to investigate the effects on intracellular iron level and biological functions, including proliferation by CKK-8 assay, colony formation, cell apoptosis and cell cycle by flow cytometry, migration and invasion, and tumor growth in vivo by nude mouse xenografts. RNA sequencing was performed to find possible mechanism after TFRC knockdown on NPC cells and further verified by western blotting. RESULTS: TfR was overexpressed in NPC cell lines and tissues. Knockdown of TFRC inhibited cell proliferation concomitant with increased apoptosis and cell cycle arrest, and it decreased intracellular iron, colony formation, migration, invasion, and epithelial-mesenchymal transition in HK1-EBV cells. Western blotting showed that TFRC knockdown suppressed the levels of the iron storage protein FTH1, anti-apoptotic marker BCL-xL, and epithelial-mesenchymal transition markers. We confirmed in vivo that TFRC knockdown also inhibited NPC tumor growth and decreased Ki67 expression in tumor tissues of nude mouse xenografts. RNA sequencing and western blotting revealed that TFRC silencing inhibited the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: These results indicated that TfR was overexpressed in NPC, and TFRC knockdown inhibited NPC progression by suppressing the PI3K/Akt/mTOR signaling pathway. Thus, TfR may serve as a novel biomarker and therapeutic target for NPC.

Characteristic genetic spectrum of primary ciliary dyskinesia in Japanese patients and global ethnic heterogeneity: population-based genomic variation database analysis.

Primary ciliary dyskinesia (PCD) is a hereditary disease caused by pathogenic variants in genes associated with motile cilia. Some variants responsible for PCD are reported to be ethnic-specific or geographical-specific. To identify the responsible PCD variants of Japanese PCD patients, we performed next-generation sequencing of a panel of 32 PCD genes or whole-exome sequencing in 26 newly identified Japanese PCD families. We then combined their genetic data with those from 40 Japanese PCD families reported previously, for an overall analysis of 66 unrelated Japanese PCD families. We conducted Genome Aggregation Database and TogoVar database analyses to reveal the PCD genetic spectrum of the Japanese population and compare with other ethnic groups worldwide. We identified 22 unreported variants among the 31 patients in the 26 newly identified PCD families, including 17 deleterious variants estimated to cause lack of transcription or nonsense-mediated mRNA decay and 5 missense mutations. In all 76 PCD patients from the 66 Japanese families, we identified 53 variants on 141 alleles in total. Copy number variation in DRC1 is the most frequent variant in Japanese PCD patients, followed by DNAH5 c.9018C>T. We found 30 variants specific to the Japanese population, of which 22 are novel. Furthermore, 11 responsible variants in the Japanese PCD patients are common in East Asian populations, while some variants are more frequent in other ethnic groups. In conclusion, PCD is genetically heterogeneous between different ethnicities, and Japanese PCD patients have a characteristic genetic spectrum.

A Novel Homozygous Variant in GAS2L2 in Two Sisters with Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare hereditary disease. We herein report two sisters in their 20s with suspected PCD. They were both born at full term and did not have situs inversus. Chest computed tomography showed similar signs of bronchiectasis in both siblings. Genetic examinations of the family confirmed that the sisters both harbored a homozygous variant in the growth-arrest-specific 2-like 2 (GAS2L2) gene. This is the third report of a family with PCD caused by a GAS2L2 variant.

Analysis of the clinical features of Japanese patients with primary ciliary dyskinesia.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a rare hereditary disease. Most reports of PCD in Japan are case reports, and clinical analysis has not been performed. Differences in the causative genes might affect the clinical features in different ethnic groups. The purpose of this study was to clarify the clinical features of Japanese patients with PCD. METHODS: We performed a retrospective chart review of PCD patients seen at Mie University Hospital and patients whose blood samples were sent to us for genetic analysis from 2011 to 2020. Data on the following items were collected and analyzed: age at first visit to the hospital, age at diagnosis of PCD, process of referral to our facility, chief complaint, situs status, PrImary CiliARy DyskinesiA Rule (PICADAR) score, nasal nitric oxide concentration, otoscopic findings, rhinoscopic findings, and paranasal computed tomography scan findings. RESULTS: Sixty-seven patients (24 male, 43 female) were diagnosed with PCD during the study period. Age at diagnosis ranged from 2 months to 69 years (median, 17 years). Respiratory symptoms (77%) were the most common complaint, followed by nasal (15%) and aural (8%) symptoms. Situs inversus was present in 17 (25%) cases. Only 2 cases had congenital cardiac anomalies. The mean PICADAR score was 7.3 (range, 3-14) points. Approximately 50% of tympanic membranes showed retraction, suggesting otitis media with effusion. The mean Lund-Mackay score was 12.8 (range, 7-17) points, suggesting that the radiographic findings were not always severe. There was no significant difference in the total Lund-Mackay score between patients with and without situs inversus (12.7 vs. 12.6, respectively). CONCLUSION: Situs inversus was present in 25% of Japanese PCD patients, which is much lower than observed in other countries. This is a result of differences in the major disease-causing genes. The general rule that "situs inversus is observed in approximately 50% of PCD patients" cannot be applied, at least, in Japanese PCD patients.

GDF10 inhibits cell proliferation and epithelial-mesenchymal transition in nasopharyngeal carcinoma by the transforming growth factor-ß/Smad and NF-κB pathways.

Growth differentiation factor-10 (GDF10) belongs to a member of the transforming growth factor-ß (TGF-ß) superfamily. Dysfunction of the TGF-ß pathway can lead to carcinoma progression. Previous studies have shown that GDF10 acts as a tumor suppressor gene in some cancers. However, the molecular mechanisms of the association between GDF10 and cell functions in nasopharyngeal carcinoma (NPC) remain unclear. In this study, the expression and methylation levels of GDF10 were studied in human subjects and cell lines. Furthermore, overexpression of GDF10 was used to explore its biological function and potential mechanism in NPC cell lines. GDF10 was downregulated in NPC owing to its aberrant promoter methylation. After treatment with 5-aza-2'-deoxycytidine, the expression of GDF10 in NPC cells was reversed. We also confirmed that the overexpression of GDF10 significantly inhibited cell proliferation and tumor growth both in vitro and in vivo, respectively. Additionally, GDF10 overexpression in NPC cells attenuated migration and invasion and inhibited epithelial-to-mesenchymal transition with a decrease in nuclear Smad2 and NF-κB protein accumulation. GDF10 was silenced owing to its promoter hypermethylation, and it might originally act as a functional tumor suppressor via TGF-ß/Smad and NF-κB signaling pathways in NPC.

A comprehensive risk score for effective risk stratification and screening of nasopharyngeal carcinoma.

Using Epstein-Barr virus (EBV)-based markers to screen populations at high risk for nasopharyngeal carcinoma (NPC) is an attractive preventive approach. Here, we develop a comprehensive risk score (CRS) that combines risk effects of EBV and human genetics for NPC risk stratification and validate this CRS within an independent, population-based dataset. Comparing the top decile with the bottom quintile of CRSs, the odds ratio of developing NPC is 21 (95% confidence interval: 12-37) in the validation dataset. When combining the top quintile of CRS with EBV serology tests currently used for NPC screening in southern China, the positive prediction value of screening increases from 4.70% (serology test alone) to 43.24% (CRS plus serology test). By identifying individuals at a monogenic level of NPC risk, this CRS approach provides opportunities for personalized risk prediction and population screening in endemic areas for the early diagnosis and secondary prevention of NPC.

Influence of Epstein-Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma.

BACKGROUND: To assess the effects of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC). METHODS: A tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed. RESULTS: We found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues. CONCLUSIONS: It is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.

STMN1 and MKI67 Are Upregulated in Uterine Leiomyosarcoma and Are Potential Biomarkers for its Diagnosis.

BACKGROUND The aim of this study was to investigate STMN1 and MKI67 expression in uterine leiomyosarcoma and their potential roles as biomarkers for diagnosis. MATERIAL AND METHODS The expression of STMN1 and MKI67 mRNA in uterine leiomyosarcoma were investigated in TCGA database. The overall survival (OS) and disease-free survival (DFS) were compared between high and low expression groups. Seventy-two patients who received hysterectomy were included and divided into 4 groups: uterine normal smooth muscle tissue (UNSM=30), uterine leiomyoma (UL=30), uterine cellular leiomyoma (UCL=24), and uterine leiomyosarcoma (ULS=18). The STMN1 and MKI67 protein expression of the 4 groups were examined by immunohistochemistry (IHC) assay. RESULTS The expression level of STMN1 mRNA in cancer tissue was significantly higher than those of normal uterine smooth muscle tissue. The high and low expression of STMN1 and mki67 gene mRNA was not related to the patients' OS and DFS (P>0.05). The positive rate of STMN1 protein in uterine leiomyosarcoma was 100.00%, which was significantly higher than that of the other 3 groups (χ²=11.72, P=0.008). And the positive rate of KIM67 protein in uterine leiomyosarcoma was 77.78%, which was also significantly higher than that of the other 3 groups (χ²=48.89, P=0.000). The diagnostic sensitivity and specificity were 77.78%, 90.74% for STMN1 combined MKI67 with the positive predictive value and negative predictive value of 73.68% and 92.45%, respectively. CONCLUSIONS STMN1 and MKI67 were upregulated in uterine leiomyosarcoma and act as potential biomarkers for uterine leiomyosarcoma diagnosis.

Alteration and prognostic values of collagen gene expression in patients with gastric cancer under different treatments.

Collagen (COL) genes participate in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways, which play a crucial role in tumor invasion and metastasis. The prognostic value of COL genes has been shown for several malignancies. In the present study, we analyzed multiple microarray datasets using the Oncomine database to identify alterations of COL genes in gastric cancer (GC). Gene expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) in GC tissues and matched adjacent tissues. The prognostic value of differentially expressed COL genes in GC was evaluated by Kaplan-Meier survival analysis based on the complete mRNA transcriptomics data from The Cancer Genome Atlas (TCGA). We found that seven COL genes (COL1A2, COL4A1, COL4A2, COL6A1, COL6A2, COL6A3, and COL11A1) were elevated in GC. Among them, stepwise multivariate Cox regression was applied, and it was determined that COL4A1 and COL4A2 were signature and independent prognostic biomarkers in GC patients with obviously different overall survival (OS). High expression of COL4A1, COL4A2, COL6A1, COL6A2, and COL6A3 was correlated with poorer prognosis of GC patients treated by surgery only, while higher expression of COL4A1 and COL11A1 correlated with poorer survival of patients treated by 5-fluorouracil-based adjuvant therapy. Our results indicate that overexpression of COL genes might be utilized as novel prognostic markers for GC and assist with therapy selection.

Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling.

Rab11 family interacting protein 2 (Rab11-FIP2) is a conserved protein and effector molecule for the small GTPase Rab11. By interacting with Rab11 and MYO5B, Rab11-FIP2 regulates endosome trafficking of plasma membrane proteins, promoting cellular motility. The endosomal trafficking system in nasopharyngeal carcinoma (NPC) remains unclear. Here, an outlier analysis using the Oncomine database suggested that Rab11-FIP2 but not Rab11 and MYO5B was overexpressed in NPC. We confirmed that the transcription of Rab11-FIP2 was upregulated in NPC cell lines and primary tumor tissues as compared with a normal nasopharyngeal epithelial cell line and normal nasopharynx tissues. We further confirmed the elevated protein expression level of Rab11-FIP2 in NPC biopsies. Instead of regulating the epithelial-mesenchymal transition or Akt signaling pathway, knockdown of Rab11-FIP2 inhibited the migration and invasion ability of NPC cell lines by decreasing the expression of Rac and Cdc42. In summary, Rab11-FIP2 could be an oncogene in NPC, mainly contributing to metastatic capacity by activating Rho GTPase signaling.

Inactivation of 3-hydroxybutyrate dehydrogenase type 2 promotes proliferation and metastasis of nasopharyngeal carcinoma by iron retention.

BACKGROUND: 3-Hydroxybutyrate dehydrogenase type 2 (BDH2) is known to catalyse a rate-limiting step in the biogenesis of the mammalian siderophore and regulate intracellular iron metabolism. Here we aim to explore the expression and possible function of BDH2 in nasopharyngeal carcinoma (NPC). METHODS: The transcription and protein expression of BDH2 in NPC were determined by both real-time RT-PCR and immunohistochemistry staining assays. Cell proliferation, migration and invasion were evaluated by MTT assay, wound-healing assay and Transwell assay, respectively. The profile of genes regulated by restoring BDH2 expression in NPC cells was analysed by cDNA microarray. The level of iron in NPC cells was detected by iron colorimetric assay. RESULTS: The expression of BDH2 was significantly downregulated in NPC. Ectopic expression of BDH2 inhibited NPC cell proliferation and colony formation. Meanwhile, BDH2 suppressed the migration and invasion of NPC cells by reversing the epithelial-mesenchymal transition (EMT). In addition, a higher level of BDH2 decreased the growth and metastasis of NPC cells via reducing intracellular iron level. CONCLUSIONS: Our findings suggest that BDH2 may be a candidate tumour-suppressor gene in NPC. Decreasing intracellular iron could be an effective therapeutic approach for NPC.

An Inflammation-Immunity Classifier of 11 Chemokines for Prediction of Overall Survival in Head and Neck Squamous Cell Carcinoma.

BACKGROUND Chemokines are important in inflammation, immunity, tumor progression, and metastasis. The purpose of this research was to find an integrated-RNA signature of chemokine family genes to predict the survival prognosis in head and neck squamous carcinoma (HNSC) patients. MATERIAL AND METHODS Relevant data of 504 HNSC patients were extracted from The Cancer Genome Atlas (TCGA) database. Through analyzing RNA sequencing data, the univariate Cox model was used to identify chemokine family genes associated with survival and then to develop a multiple-RNA signature in the training set. The prediction value of this multiple-RNA signature was further verified in the validation and entire sets. The receiver operating characteristic curves were used to assess the predictive value of this multiple-RNA signature. RESULTS Eleven chemokines were included in this prognostic signature. Based on this 11-chemokine signature, we further categorized patients as high or low risk. Compared with low-risk patients, high-risk patients had shorter overall survival (OS) time in the training set [hazard ratio (HR)=3.497, 95% confidence interval (CI)=2.142-5.711, p<0.001], validation set (HR=3.575, 95% CI=1.988-6.390, p<0.001), and entire set (HR=3.416, 95% CI=2.363-4.939, p<0.001). This 11-chemokine signature was an independent prognostic factor for OS in these datasets (p<0.05). The AUC values for predicting overall survival within 48 months in the training, validation, and entire sets were 0.71, 0.69, and 0.69, respectively. CONCLUSIONS This 11-chemokine signature could serve as a reliable prognostic tool for HNSC patients and might be useful to guide individualized treatment or even gene target therapy for high-risk patients.

Caffeic acid phenethyl ester suppressed growth and metastasis of nasopharyngeal carcinoma cells by inactivating the NF-κB pathway.

Purpose: Caffeic acid phenethyl ester (CAPE) is the main polyphenol extracted from honeybee propolis, which inhibits the growth of several kinds of tumor. This study aimed to assess the inhibitory effect of CAPE in nasopharyngeal carcinoma (NPC), evaluate the synergistic action of CAPE in radiotherapy sensitivity of NPC cell lines and further elucidate the possible molecular mechanism involved. Materials and methods: CCK-8 assay was used to analyze cell proliferation ability. Colony formation assay was used to evaluate the clonogenic ability and radio-sensitiveness of NPC cells by CAPE treatment. Wound-healing and transwell assay were used to assess the motility of cells. The expression of key molecules of the epithelial-mesenchymal transition (EMT) was determined by western blot analysis and changes in radiation sensitivity were measured by colony-formation assay. cDNA microarray analysis was used to determine differentially expressed genes with and without CAPE treatment, with Gene Ontology enrichment of gene function and KEGG pathways determined. Cell cycle and apoptosis were detected by flow cytometry and western blot analysis. Results: CAPE suppressed the viability of NPC cell lines time- and dose-dependently. It induced apoptosis in NPC cells along with decreased expression of Bcl-XL and increased cleavage of PARP and expression of Bax. G1 phase arrest was induced by CAPE with ower expression of CDK4, CDK6, Rb and p-Rb. The migratory and invasive ability of NPC cells was decreased by the EMT pathway. The irradiation sensitivity of NPC cells was enhanced with CAPE treatment. CAPE specifically inhibited nuclear factor κB (NF-κB) signaling pathway by suppressing p65 subunit translocation from cytoplasm to nucleus. CAPE treatment was synergistic with chemotherapy and radiotherapy. Conclusion: CAPE may inhibit the proliferation and metastasis of NPC cells but enhance radiosensitivity in NPC therapy by inhibiting the NF-κB pathway. CAPE could be a potential therapeutic compound for NPC therapy.

Dysregulation of Ketone Body Metabolism Is Associated With Poor Prognosis for Clear Cell Renal Cell Carcinoma Patients.

Kidney is an important organ for ketone body metabolism. However, the role of abnormal ketone metabolism and its possible function in tumorigenesis of clear cell renal cell carcinoma (ccRCC) have not yet been elucidated. Three differentially expressed key enzymes involved in ketone body metabolism, ACAT1, BDH2, and HMGCL, were screened out between ccRCC and normal kidney tissues using the GEO and TCGA databases.We confirmed that the transcription and protein expression of ACAT1, BDH2, and HMGCL were significantly lower in ccRCC by real-time RT-PCR and IHC assays. Those patients with lower expression of these three genes have a worse outcome. In addition, we demonstrated that ectopic expression of each of these genes inhibited the proliferation of ccRCC cells. The overexpressed ACAT1 and BDH2 genes remarkably impeded the migratory and invasive capacity of ccRCC cells. Furthermore, exogenous ß-hydroxybutyrate suppressed the growth of ccRCC cells in vitro in a dose-dependent manner. Our findings suggest that ACAT1, BDH2, and HMGCL are potential tumor suppressor genes, and constitute effective prognostic biomarkers for ccRCC. Ketone body metabolism might thus be a promising target in a process for developing novel therapeutic approaches to treat ccRCC.

Optimal Design of Low-Density SNP Arrays for Genomic Prediction: Algorithm and Applications.

Low-density (LD) single nucleotide polymorphism (SNP) arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for the optimal design of LD SNP chips. A multiple-objective, local optimization (MOLO) algorithm was developed for design of optimal LD SNP chips that can be imputed accurately to medium-density (MD) or high-density (HD) SNP genotypes for genomic prediction. The objective function facilitates maximization of non-gap map length and system information for the SNP chip, and the latter is computed either as locus-averaged (LASE) or haplotype-averaged Shannon entropy (HASE) and adjusted for uniformity of the SNP distribution. HASE performed better than LASE with ≤1,000 SNPs, but required considerably more computing time. Nevertheless, the differences diminished when >5,000 SNPs were selected. Optimization was accomplished conditionally on the presence of SNPs that were obligated to each chromosome. The frame location of SNPs on a chip can be either uniform (evenly spaced) or non-uniform. For the latter design, a tunable empirical Beta distribution was used to guide location distribution of frame SNPs such that both ends of each chromosome were enriched with SNPs. The SNP distribution on each chromosome was finalized through the objective function that was locally and empirically maximized. This MOLO algorithm was capable of selecting a set of approximately evenly-spaced and highly-informative SNPs, which in turn led to increased imputation accuracy compared with selection solely of evenly-spaced SNPs. Imputation accuracy increased with LD chip size, and imputation error rate was extremely low for chips with ≥3,000 SNPs. Assuming that genotyping or imputation error occurs at random, imputation error rate can be viewed as the upper limit for genomic prediction error. Our results show that about 25% of imputation error rate was propagated to genomic prediction in an Angus population. The utility of this MOLO algorithm was also demonstrated in a real application, in which a 6K SNP panel was optimized conditional on 5,260 obligatory SNP selected based on SNP-trait association in U.S. Holstein animals. With this MOLO algorithm, both imputation error rate and genomic prediction error rate were minimal.

[Analysis of epidermal growth factor receptor expression and gene expression status in tissue microarray of cervical squamous cell carcinoma].

OBJECTIVE: To elucidate the protein expression and gene expression status and the relationship between epidermal growth factor receptor (EGFR) protein expression and EGFR gene status. METHODS: Tissue microarray containing 72 cervical squamous cell carcinoma tissues was constructed, and EGFR protein expression and gene status were evaluated by immunohistochemical and fluorescence in situ hybridization (FISH) techniques. RESULTS: Protein expression of EGFR: 69 of 72 cervical squamous cell carcinomas were observed. The results demonstrated it was significant association with invasion depth, lymph node metastasis and lymph-vessel invasion (χ(2) = 4.998, P < 0.05; χ(2) = 4.299, P < 0.05; χ(2) = 4.686, P < 0.05) in cervical squamous cell carcinomas. For FISH assessing EGFR gene, 64 of 72 carcinomas were observed; 7 of 64 cases showed EGFR gene amplification, and 25 disomy, 23 trisomy and 9 polysomy were detected. There were high levels of protein expression in all the EGFR gene amplification cases, and there were significant association between EGFR protein expression and the gene copy number (χ(2) = 13.564, P < 0.05). CONCLUSIONS: EGFR may participate in the occurrence, progression and metastasis of cervical squamous cell carcinoma. Overexpression of EGFR protein may result from gene amplification and gene copy number increases, which showed that EGFR gene expression status may be a more effective biological indicator of cervical squamous cell carcinoma targeted therapy.

[The expression and clinical pathological significance of PDCD in laryngocarcinoma].

OBJECTIVE: To investigate the expression and clinical pathological significance of PDCD4 in laryngocarcinoma tissue and its potential significance to clinic. METHOD: Western-blotting and immunohistochemistry ana lyse to measure the protein expression of PDCD4 in 54 cases of laryngocarcinoma tissues (studying group) and their paraneoplastic normal tissues (control group). The correlations of PDCD4 with clinical pathological parameters were analyzed. RESULT: PDCD4 protein was positively expressed in paraneoplastic normal tissue while which was lost or decreased in laryngocarcinoma tissue by Western blot and immunohistochemistry. Immunohistochemistry assay showed the location of PDCD4 protein in cells was different between the studying group and the control group. The expression level of PDCD4 was related to the pathological grades of the laryngocarcinoma. It's higher in the well-differentiated tumor group than that in the poorly differentiated ones. But the expressions of PDCD4 were no differences among other clinical parameters including sex, age, clinical classification, clinical stage and the cervical lymphonodus who had been metastases or not. CONCLUSION: PDCD4 gene is anti-oncogene. It may play an important role in the pathogenesis and development of laryngeal carcinoma and it may be a new target of therapy for laryngo carcinoma.

[Correlation between orthostatic hypotension and cardiovascular risks in elderly population].

OBJECTIVE: To investigate the correlation between orthostatic hypotension and cardiovascular risks and hospitalization rate in the elders. METHODS: A total of 1174 people over 65 years old underwent health screening physical examination through a self-made questionnaire at our hospital. Their clinical data were collected. The orthostatic blood pressure and heart rate were measured in supine position after resting for over 5 minutes and at 0 and 2 min after standing. Orthostatic hypotension was defined as 20 mm Hg or greater decrease in SBP or/and 10 mm Hg or greater decrease in DBP after standing. All cases were followed up by telephone or hospitalization medical records for a mean period of 315.8 days. The primary endpoint was the occurrence of such cardiovascular or cerebrovascular events as angina, fatal or nonfatal myocardial infarction (MI), congestive heart failure, sudden cardiac death, ischemic and hemorrhagic stroke. RESULTS: The prevalence of OH was 25.6% in this cohort. Significant differences could be found in the rate of all-cause and cardiovascular-related hospitalization between OH positive and OH negative (45.1% vs 32.5%; 19.1% vs 7.4%); the rates of angina and myocardial infarction in the OH positive group were significantly higher than those in the OH negative group (7.5% vs 3.7%: 4.8% vs 0.5%, P < 0.05); after adjusting for age, supine blood pressure, heart rate and cerebrovascular history by logistic regression, statistical differences could also be observed between OH and angina [P = 0.011, HR (hazard ratio): 2.122, 95%CI (confidence interval): 1.184-3.802 and MI (P < 0.001, HR: 8.995, 95%CI: 2.909 - 27.819)]. CONCLUSION: Orthostatic hypotension may increase the rates of all-cause and cardiovasular-related hospitalization. And it is a robust predictor of angina and myocardial infarction in the elders.