Phylogenetics, Genomic Recombination, and NSP2 Polymorphic Patterns of Porcine Reproductive and Respiratory Syndrome Virus in China and the United States in 2014-2018.

Porcine reproductive and respiratory syndrome virus (PRRSV), an important pathogen that affects the pig industry, is a highly genetically diverse RNA virus. However, the phylogenetic and genomic recombination properties of this virus have not been completely elucidated. In this study, comparative analyses of all available genomic sequences of North American (NA)-type PRRSVs (n = 355, including 138 PRRSV genomes sequenced in this study) in China and the United States during 2014-2018 revealed a high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and the GP2 to GP3 regions. Lineage 1 (L1) PRRSV was found to be susceptible to recombination among PRRSVs both in China and the United States. The recombinant major parent between the 1991-2013 data and the 2014-2018 data showed a trend from complex to simple. The major recombination pattern changed from an L8 to L1 backbone during 2014-2018 for Chinese PRRSVs, whereas L1 was always the major backbone for US PRRSVs. Intralineage recombination hot spots were not as concentrated as interlineage recombination hot spots. In the two main clades with differential diversity in L1, NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, NADC34-like PRRSVs have been relatively stable in population genetic diversity for years. Systematic analyses of insertion and deletion (indel) polymorphisms of NSP2 divided PRRSVs into 25 patterns, which could generate novel references for the classification of PRRSVs. The results of this study contribute to a deeper understanding of the recombination of PRRSVs and indicate the need for coordinated epidemiological investigations among countries.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases. However, the phylogenetic and genomic recombination properties of the PRRS virus (PRRSV) have not been completely elucidated. In this study, we systematically compared differences in the lineage distribution, recombination, NSP2 polymorphisms, and evolutionary dynamics between North American (NA)-type PRRSVs in China and in the United States. Strikingly, we found high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and in the GP2 to GP3 region. Also, intralineage recombination hot spots were scattered across the genome between Chinese and US strains. Furthermore, we proposed novel methods based on NSP2 indel patterns for the classification of PRRSVs. Evolutionary dynamics analysis revealed that NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, suggesting that a dominant population may occur and cause an outbreak. Our findings offer important insights into the recombination of PRRSVs and suggest the need for coordinated international epidemiological investigations.

Discovery of Novel Bat Coronaviruses in South China That Use the Same Receptor as Middle East Respiratory Syndrome Coronavirus.

Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs that belong to the same species as MERS-CoV have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus coronavirus HKU4, Pipistrellus pipistrelluscoronavirus HKU5, and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io, from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein-protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs have acquired their spike genes from a DPP4-recognizing bat coronavirus HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV.IMPORTANCE Previous studies suggested that MERS-CoV originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses in eight bat species. We provide evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus, HKU4. Our study expands the host ranges of MERS-related CoV and represents an important step toward establishing bats as the natural reservoir of MERS-CoV. These findings may lead to improved epidemiological surveillance of MERS-CoV and the prevention and control of the spread of MERS-CoV to humans.

Novel bat adenoviruses with low G+C content shed new light on the evolution of adenoviruses.

Bats have been reported to carry diverse adenoviruses. However, most bat adenoviruses have been identified on the basis of partial genome sequences, and knowledge on the evolution of bat adenoviruses remains limited. In this study, we isolated and characterized four novel adenoviruses from two distinct bat species, and their full-length genomes were sequenced. Sequence analysis revealed that these isolates represented three distinct species of the genus Mastadenovirus. However, all isolates had an exceptionally low G+C content and relatively short genomes compared with other known mastadenoviruses. We further analysed the relationships among the G+C content, 5'-C-phosphate-G-3' (CpG) representation and genome size in the family Adenoviridae. Our results revealed that the CpG representation in adenoviral genomes depends primarily on the level of methylation, and the genome size displayed significant positive correlations with both G+C content and CpG representation. Since ancestral adenoviruses are believed to have contained short genomes, those probably had a low G+C content, similar to the genomes of these bat strains. Our results suggest that bats are important natural reservoirs for adenoviruses and play important roles in the evolution of adenoviruses.

Emergence of genotype I of Japanese encephalitis virus as the dominant genotype in Asia.

Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis worldwide. Previous phylogenetic studies based on the envelope protein indicated that there are four genotypes, and surveillance data suggest that genotype I is gradually replacing genotype III as the dominant strain. Here we report an evolutionary analysis based on 98 full-length genome sequences of JEV, including 67 new samples isolated from humans, pigs, mosquitoes, midges. and bats in affected areas. To investigate the relationships between the genotypes and the significance of genotype I in recent epidemics, we estimated evolutionary rates, ages of common ancestors, and population demographics. Our results indicate that the genotypes diverged in the order IV, III, II, and I and that the genetic diversity of genotype III has decreased rapidly while that of genotype I has increased gradually, consistent with its emergence as the dominant genotype.

[Oleanolic acid inhibits proliferation of HUVECs, and inhibits migration and tube formation via VEGF pathway].

To investigate the effects of oleanolic acid (OA) on the proliferation, migration and the formation of tube-like structure in human vascular endothelial cells (HUVECs). MTT assay, flat plate scarification, Transwell plates and matrigel-induced tube formation assay were performed to detect the effects of OA on proliferation, migration and tube formation. MTT assay showed that the inhibition rates of HUVECs treated with 60 and 100 microg x mL(-1) of OA for 24 h were 19% and 83% respectively. Treatment of HUVECs significantly inhibited the cell migration in a dose-dependent manner. The vascular indexes of HUVECs treated with 40 and 60 microg x mL(-1) OA were 33% and 20% respectively. Western blotting analysis showed that treatment of the cells with OA significantly attenuated the expression and secretion of VEGF. Additionally, VEGF could in part reverse the effects of OA on migration and tube formation of HUVECs. In conclusion, OA inhibits the proliferation, and VEGF plays an important role in OA induced decreased migration and tube formation of HUVECs.

Cytotoxic metabolites from the soil-derived fungus Exophiala pisciphila.

A new polyketide compound 1 and a new naturally occurring chromone derivative 2, along with two known indole alkaloids 3-4 were characterized from the ethyl acetate extract of a soil-derived fungal strain, Exophiala pisciphila PHF-9. The structures of compounds 1-4 were established by detailed spectroscopic analysis and comparison with literature data. The absolute configuration of 1 was determined by a modified Mosher's method. Compound 1 exhibited moderate cytotoxicity against A-549, Hela, PANC-28 and BEL-7402 cell lines.

Genomic Characterization of Diverse Bat Coronavirus HKU10 in Hipposideros Bats.

Bats have been identified as natural reservoirs of a variety of coronaviruses. They harbor at least 19 of the 33 defined species of alpha- and betacoronaviruses. Previously, the bat coronavirus HKU10 was found in two bat species of different suborders, Rousettus leschenaultia and Hipposideros pomona, in south China. However, its geographic distribution and evolution history are not fully investigated. Here, we screened this viral species by a nested reverse transcriptase PCR in our archived samples collected over 10 years from 25 provinces of China and one province of Laos. From 8004 bat fecal samples, 26 were found to be positive for bat coronavirus HKU10 (BtCoV HKU10). New habitats of BtCoV HKU10 were found in the Yunnan, Guangxi, and Hainan Provinces of China, and Louang Namtha Province in Laos. In addition to H. pomona, BtCoV HKU10 variants were found circulating in Aselliscus stoliczkanus and Hipposideros larvatus. We sequenced full-length genomes of 17 newly discovered BtCoV HKU10 strains and compared them with previously published sequences. Our results revealed a much higher genetic diversity of BtCoV HKU10, particularly in spike genes and accessory genes. Besides the two previously reported lineages, we found six novel lineages in their new habitats, three of which were located in Yunnan province. The genotypes of these viruses are closely related to sampling locations based on polyproteins, and correlated to bat species based on spike genes. Combining phylogenetic analysis, selective pressure, and molecular-clock calculation, we demonstrated that Yunnan bats harbor a gene pool of BtCoV HKU10, with H. pomona as a natural reservoir. The cell tropism test using spike-pseudotyped lentivirus system showed that BtCoV HKU10 could enter cells from human and bat, suggesting a potential interspecies spillover. Continuous studies on these bat coronaviruses will expand our understanding of the evolution and genetic diversity of coronaviruses, and provide a prewarning of potential zoonotic diseases from bats.

Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus with high fatality and an expanding endemic. Currently, effective anti-SFTSV intervention remains unavailable. Favipiravir (T-705) was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV. Here, we conducted a single-blind, randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS (Chinese Clinical Trial Registry website, number ChiCTR1900023350). From May to August 2018, laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only. Fatal outcome occurred in 9.5% (7/74) of T-705 treated patients and 18.3% (13/71) of controls (odds ratio, 0.466, 95% CI, 0.174-1.247). Cox regression showed a significant reduction in case fatality rate (CFR) with an adjusted hazard ratio of 0.366 (95% CI, 0.142-0.944). Among the low-viral load subgroup (RT-PCR cycle threshold ≥26), T-705 treatment significantly reduced CFR from 11.5 to 1.6% (P = 0.029), while no between-arm difference was observed in the high-viral load subgroup (RT-PCR cycle threshold <26). The T-705-treated group showed shorter viral clearance, lower incidence of hemorrhagic signs, and faster recovery of laboratory abnormities compared with the controls. The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates, particularly from two transition mutation types. The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads, further supporting the anti-SFTSV effect of T-705, especially for the low-viral loads.

Characterization of catabolic meta-nitrophenol nitroreductase from Cupriavidus necator JMP134.

Cupriavidus necator JMP134 utilizes meta-nitrophenol (MNP) as a sole source of carbon, nitrogen, and energy. The metabolic reconstruction of MNP degradation performed in silico suggested that the mnp cluster might have played important roles in MNP degradation. In order to experimentally confirm the prediction, we have now characterized mnpA-encoded meta-nitrophenol nitroreductase involved in the initial reaction of MNP degradation. Real-time PCR analysis indicated that mnpA played an essential role in MNP degradation. MnpA was purified to homogeneity as His-tagged proteins and was considered to be a dimer as determined by gel filtration. MnpA was an MNP nitroreductase with a tightly bound flavin mononucleotide (FMN), catalyzing the partial reduction of MNP to meta-hydroxylaminophenol via meta-nitrosophenol in the presence of NADPH and oxygen. The accumulation of meta-nitrosophenol was confirmed with the results of liquid chromatography-diode array detection and time-of-flight mass spectrometry for the first time. The low K (m) and high k (cat) of MnpA as well as MNP-inducible transcription of mnpA suggested that MNP was the physiological substrate for this nitroreductase. In addition, the phylogenetic analysis revealed that nitroreductases of known physiological function including MnpA constituted a new clade in the nitro-FMN-reductase superfamily.

Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009-2016.

Previous studies indicated that fruit bats carry two betacoronaviruses, BatCoV HKU9 and BatCoV GCCDC1. To investigate the epidemiology and genetic diversity of these coronaviruses, we conducted a longitudinal surveillance in fruit bats in Yunnan province, China during 2009-2016. A total of 59 (10.63%) bat samples were positive for the two betacorona-viruses, 46 (8.29%) for HKU9 and 13 (2.34%) for GCCDC1, or closely related viruses. We identified a novel HKU9 strain, tentatively designated as BatCoV HKU9-2202, by sequencing the full-length genome. The BatCoV HKU9-2202 shared 83% nucleotide identity with other BatCoV HKU9 stains based on whole genome sequences. The most divergent region is in the spike protein, which only shares 68% amino acid identity with BatCoV HKU9. Quantitative PCR revealed that the intestine was the primary infection organ of BatCoV HKU9 and GCCDC1, but some HKU9 was also detected in the heart, kidney, and lung tissues of bats. This study highlights the importance of virus surveillance in natural reservoirs and emphasizes the need for preparedness against the potential spill-over of these viruses to local residents living near bat caves.

Channel Crack-Designed Gold@PU Sponge for Highly Elastic Piezoresistive Sensor with Excellent Detectability.

It is a great challenge to fabricate piezoresistive sensors that possess high elasticity, large-area compliance, and excellent detectability to satisfy both extremely tiny and large human activity monitoring. Herein, a novel and facile strategy is reported to manufacture highly elastic channel crack-based gold@PU sponge piezoresistive material. The elastic 3D conductive network is successfully prepared by gold ion sputtering, and channel cracks are skillfully designed on the 3D sponge skeletons. Such novel structure makes these fabricated sensors are capable of monitoring both tiny and large human motions, which originate from the nanocrack joint sensing mechanism and physical contact of conductive interconnected network. Meanwhile, our sensors possess excellent elasticity, fast response time (9 ms), and ultralow detection limit (0.568 Pa), as well as good reproducibility over 1000 cycles. The desirable elasticity of channel crack-based gold@PU sensor is comparable to recently reported pressure sensors, together with advantages of reliable fabrication and large-area compliance, makes them attractive in various electronic devices, for example, biological health monitoring, sport performance monitoring, and man-machine interfaces.

Associations between serum HBX quasispecies and their integration in hepatocellular carcinoma.

HBV quasispecies are closely related to the course and outcome of liver disease. However, whether the complexity and diversity of HBX quasispecies affects its integration in the liver cell and thereby enhances the resultant carcinogenesis is still not clear. 15 HCC patients were recruited; genomic DNA and HBV DNA were extracted from liver cancer tissue and serum respectively. The integrated HBX fragment in liver cancer tissue was amplified by Alu repeat sequence-polymerase chain reaction (Alu-PCR) and sequenced. The serum HBX gene was amplified by nested PCR and sequenced. Quasispecies complexity and diversity, phylogenetic characteristics, lymphocyte count and survival time between HBX-integrated and HBX-unintegrated patients were evaluated. Results showed that the integrated HBX fragment was detected in the tumor tissue of nine patients, and the integration rate was 60.00% (9/15). Compared with the HBX-unintegrated patients, the HBX-integrated patients had a higher quasispecies complexity (P=0.028 and 0.004, at the nucleotide and amino acid levels, respectively). The HBX-integrated patients had a tendency of higher quasispecies diversity, lower lymphocyte count and the survival time. A total of 12 mutation sites were revealed in the HBX-integrated fragment after alignment with the reference sequence. In these, the HBX-integrated groups had significantly higher mutation frequencies at C1497T, A1630G, G1721A, A1762T/G1764A and A1774G. This study revealed influence factors of HBX integration both in virus and the host. The increased complexity and diversity of HBX quasispecies might destroy the host immune balance, and lead to HBX integration ultimately.

Flowers of Camellia nitidissima cause growth inhibition, cell-cycle dysregulation and apoptosis in a human esophageal squamous cell carcinoma cell line.

The present study aimed to investigate the chemopreventive effect of Camellia nitidissima flowers water extract (CNFE) on the Eca109 human esophageal squamous cell carcinoma (ESCC) cell line. The antiproliferative effect on Eca109 cells was determined using the trypan blue exclusion assay. The effects of CNFE on apoptosis and cell cycle arrest were investigated by flow cytometry. CNFE inhibited cell growth in both a dose­ and time­dependent manner in Eca109 cells. CNFE also caused dose­ and time­dependent apoptosis of these cells. Treatment of cells with CNFE resulted in dose­dependent G0/G1 phase arrest of the cell cycle. The data demonstrated that CNFE serves antiproliferative effects against human ESCC Eca109 cells by inducing apoptosis and interrupting the cell cycle. These results suggested that CNFE has the potential to be a chemoprotective agent for ESCC.

Peripheral blood lymphocyte subset levels differ in patients with hepatocellular carcinoma.

We investigated the levels of target lymphocyte subsets in peripheral blood lymphocyte samples from patients with hepatocellular carcinoma (HCC). A total of 715 high-risk patients with primary HCC were recruited in Guangxi, China as the case group. The control group included 100 patients who received health examinations at the same hospital during the same period. Fasting elbow venous blood (10 mL) was collected from each participant, and flow cytometry was used to detect the levels of NK cells and CD3+, CD4+ and CD19+ T cells in peripheral blood samples. All included patients with prmary HCC were treated by surgical resection, and followed up for one year. The levels of CD19+ and NK cells were lower in cases than in controls (both P < 0.05). In addition, the level of CD8+ cells was greater in the case group than in the control group (P < 0.05). In the high-HCC-risk population, CD8+, CD19+ and NK cell levels all differed between male and female patients, patients in TNM stages I-II and stages III-IV, patients with and without extrahepatic metastasis, and patients with and without HBV infection (all P < 0.05). After follow-up, detected recurrence and survival rate was 33.71% and 83.64%, respectively. CD8+ levels was reduced following surgical resection, whereas the levels of CD19+ and NK cells were increased (all P < 0.05). In conclusion, altered levels of CD8+, CD19+ and NK cell levels may be used as reference values for monitoring immune function in certain populations with high HCC risk, and as potential evidence for the clinical diagnosis and treatment of HCC.

An Analysis of EGFR Mutations among 1506 Cases of Non-Small Cell Lung Cancer Patients in Guangxi, China.

An association between epidermal growth factor receptor (EGFR) and clinical characteristics of non-small cell lung cancer (NSCLC) was reported ten years ago. In addition, a different type of relationship was seen in different ethic races. However, the relationship between these factors is not well understood in the Guangxi province. Up to now, there are only very limited data on the association of TTF1/EGFR protein positivity and EGFR mutation status in NSCLC. This study aims to investigate the role of EGFR gene mutation status on the clinical characteristics and the relationship with TTF-1/EGFR protein positivity of patients with NSCLC in Guangxi, China. 1506 samples from different patients with NSCLC were detected by amplification refractory mutation system for 29 hotspot mutations. Analysis of the relationship between clinical characteristics and EGFR mutation status was performed by using the crosstabs Chi-square and SPSS 21.0 software. Of 1506 samples, 537 (35.7%) revealed tyrosine kinase inhibitor (TKI) sensitive EGFR mutations with 27 (1.8%) cases harboring TKI resistant EGFR mutations or union co-existing EGFR-TKIs sensitive mutations. EGFR-TKIs sensitive mutations were not significantly associated with age and TNM-M stage (P = 0.863; P = 0.572, respectively). However, they were significantly associated with p-stage, TNM-T stage and TNM-N stage (P = 0.011, P < 0.001, P = 0.036, respectively). Immunohistochemical studies revealed that TTF-1 and EGFR protein expression level were all associated with EGFR mutation status (P < 0.001, P = 0.002, respectively). Of the 537 EGFR-TKIs sensitive mutation cases, the rates of exon 19-del, 18 G719X point, exon 21 L858R and L861Q points were 54.6, 0.9, 42.3 and 0.9%, respectively. EGFR TKI-sensitive mutations commonly occur in female, non-smoking and adenocarcinoma patients. The p-stage, TNM-T stage, TNM-N stage, EGFR and TTF-1 protein expression levels have close relationships with EGFR mutation status.

Screening and preliminary validation of miRNAs with the regulation of hTERT in colorectal cancer.

The overexpression of human telomerase reverse transcriptase (hTERT) has been associated with the invasion and metastasis of colorectal cancer (CRC) and has received extensive attention, although the underlying mechanism involved remains unclear. The aim of the present study was to screen and preliminarily validate new tumor­suppressor microRNAs (miRNAs) that potentially inhibit hTERT expression and to assess its clinical significance. Screening for downregulated miRNAs in CRC tissues was performed by retrieving and analysing microRNA microarray data. miRNA candidates were then filtered by bioinformatics analysis. The expression of miRNAs candidates was verified by quantitative polymerase chain reaction in the CRC and corresponding normal tissues. Immunohistochemistry (IHC) was used for the detection of hTERT protein expression. Spearman's correlation coefficient between miRNA candidates and hTERT protein expression was calculated (r) to identify hTERT-targeting miRNAs. A survival analysis was performed to assess the prognostic significance of hTERT-targeting miRNAs in CRC. Eight miRNAs with the potential to interact with hTERT were predicted: miR­29c-3p, miR­124-3p, miR­133a-3p, miR­133b, miR-138-5p, miR-150-5p, miR-378a-3p and miR-422a, respectively. Following detection of the miRNAs using RT-qPCR, miR-29c-3p was excluded. miR-138-5p and miR-422a were observed to potentially interact with hTERT (r=-0.362, P=0.001; r=-0.306, P=0.005, respectively). The Kaplan-Meier survival curves demonstrating high- vs. low-expression group of miR­422a showed a highly significant difference in CRC patients (P=0.024), which suggests that the downregulation of miR-422a was associated with a poorer prognosis. The results indicated that miR-138-5p and miR-422a potentially inhibited hTERT expression in CRC, and suggest a potential application of miR­422a in prognosis prediction and CRC treatment.

Anisotropic patterns of liver cancer prevalence in Guangxi in Southwest China: is local climate a contributing factor?

Geographic information system (GIS) technology has useful applications for epidemiology, enabling the detection of spatial patterns of disease dispersion and locating geographic areas at increased risk. In this study, we applied GIS technology to characterize the spatial pattern of mortality due to liver cancer in the autonomous region of Guangxi Zhuang in southwest China. A database with liver cancer mortality data for 1971-1973, 1990-1992, and 2004-2005, including geographic locations and climate conditions, was constructed, and the appropriate associations were investigated. It was found that the regions with the highest mortality rates were central Guangxi with Guigang City at the center, and southwest Guangxi centered in Fusui County. Regions with the lowest mortality rates were eastern Guangxi with Pingnan County at the center, and northern Guangxi centered in Sanjiang and Rongshui counties. Regarding climate conditions, in the 1990s the mortality rate of liver cancer positively correlated with average temperature and average minimum temperature, and negatively correlated with average precipitation. In 2004 through 2005, mortality due to liver cancer positively correlated with the average minimum temperature. Regions of high mortality had lower average humidity and higher average barometric pressure than did regions of low mortality. Our results provide information to benefit development of a regional liver cancer prevention program in Guangxi, and provide important information and a reference for exploring causes of liver cancer.

Mortality of major cancers in Guangxi, China: sex, age and geographical differences from 1971 and 2005.

The incidence and mortality rates of liver and nasopharyngeal cancer in Guangxi province of China have always been among the highest in the world, and cancer is one of the major diseases that pose a threat to the health of residents in Guangxi. However, no systematic study has been performed to evaluate the time trends in the structure of cancer-related deaths and cancer mortality. In this study, we reveal sex, age and geography differences of cancers mortality between three death surveys (1971 to 1973, 1990 to 1992, and 2004 to 2005). The results show that the standardized mortality rate of cancer in Guangxi residents has risen from 43.3/100,000 to 84.2/100,000, the share of cancer deaths in all-cause deaths has increased from 13.3% to 20.7%, and cancer has become the second most common cause of death. The five major cancers, liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and colorectal cancer, account for 60% of all the cancer deaths. Cancers with growing mortality rates over the past 30 years include lung cancer, colorectal cancer, liver cancer and female breast cancer, of which lung cancer is associated with the sharpest rise in mortality, with a more than 600% rise in both men and women. Cancer death in Guangxi residents occurs mainly in the elderly population above 45 years of age, especially in people over the age of 65. The areas with the highest mortality rates for liver cancer and nasopharyngeal cancer, which feature regional high incidences, include Chongzuo and Wuzhou. Therefore, for major cancers such as liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and female breast cancer in Guangxi, we can select high-risk age groups as the target population for cancer prevention and control efforts in high-prevalence areas in a bid to achieve the ultimate goal of lowering cancer mortality in Guangxi.

Human epidermal growth factor receptor 2 expression in breast cancer: correlation with clinical pathological features.

The overexpressed HER2 (human epidermal growth factor receptor 2) is a valuable therapeutic target. Precise assessment of HER2 status is thus crucial in the treatment of breast cancer. In this study, formalin-fixed, paraffin-embedded samples of tumors from 304 breast cancer patients who underwent curative surgery procedures between 2011 and 2014 were tested by immunohistochemistry (IHC) as a primary estimate of HER2 status, followed by fluorescence in situ hybridization (FISH). Concordance rate between IHC and FISH was evaluated. The Χ(2) test was used to evaluate the correlation between HER2 gene amplification status and different clinical pathological features including: (estrogen receptor) ER and (progesterone receptor) PR expression, age, menopausal status and tumor size. The results show that 84.8% of IHC score 3+ cases and 6.2% of IHC score 0/1+ cases were amplified by FISH. After exclusion of group IHC 2+, the concordance rate between FISH and IHC was 87.4%. There was a significant inverse association between expression of hormone receptors (ER and PR) and HER2 amplification (P < 0.001) among the patients studied. However, no relationship was observed between HER2 amplification and age, menopausal status and tumor size (P > 0.05). The data demonstrate a relatively high level of concordance rate for HER2 testing between FISH and IHC, and HER2 overexpression was associated with the levels of ER and PR.

Use of mutual information arrays to predict coevolving sites in the full length HIV gp120 protein for subtypes B and C.

It is well established that different sites within a protein evolve at different rates according to their role within the protein; identification of these correlated mutations can aid in tasks such as ab initio protein structure, structure function analysis or sequence alignment. Mutual Information is a standard measure for coevolution between two sites but its application is limited by signal to noise ratio. In this work we report a preliminary study to investigate whether larger sequence sets could circumvent this problem by calculating mutual information arrays for two sets of drug naïve sequences from the HIV gp120 protein for the B and C subtypes. Our results suggest that while the larger sequences sets can improve the signal to noise ratio, the gain is offset by the high mutation rate of the HIV virus which makes it more difficult to achieve consistent alignments. Nevertheless, we were able to predict a number of coevolving sites that were supported by previous experimental studies as well as a region close to the C terminal of the protein that was highly variable in the C subtype but highly conserved in the B subtype.