Effects of Simulated Microgravity on Acquired Antibiotic Resistance in Klebsiella pneumoniae Exposed to Trace Antibiotic.

Objective: The purpose of this study is to gain a better understanding of the impact of microgravity on antibiotic resistance. Methods: K. pneumoniae original (KPO) strain was cultured under either simulated microgravity (SMG) conditions with background antibiotic exposure (SMGA) for the experimental strain or a normal gravity condition with background antibiotic exposure (NGA) for the control strain. The K. pneumoniae original (KPO) strain was also cultured under normal gravity (NG) as an additional control. Antibiotic susceptibility was evaluated prior to their incubation under SMGA, NGA, or NG conditions. After 20 cycles of incubation, antibiotic susceptibility, genomic, transcriptomic, and proteomic tests were conducted on them. Results: SMGA and NGA strains both showed resistance to ciprofloxacin and intermediate resistance to levofloxacin. Genes associated with antibiotic resistance of Klebsiella pneumoniae, including acrB, oqxB, oqxA, ompC, ompF, and tolC were found to be differently expressed between SMGA and NGA strains or between SMGA and NG strains. It was found that the biggest family of genes in the differently expressed gene (DEG) cluster between SMGA and NGA and between SMGA and NG was the same, paaBCDFGHI, but with opposite change direction, i.e., downregulation between SMGA and NGA strains, while upregulation between SMGA and NG strains. Besides, the top-ranking functional descriptions in terms of the number of DEGs whether between SMGA and NGA or between SMGA and NG were "amino acid transport and metabolism", "carbohydrate transport and metabolism", "transcription", and "inorganic ion transport and metabolism". Two pathways of "citrate cycle (TCA cycle)" and "oxidative phosphorylation" were significantly enriched by DEGs both between SMGA and NGA and between SMGA and NG. Conclusion: Our study confirmed that low levels of antibiotics present in SMG can select for resistant K. pneumoniae strains. However, SMG did not alter the antibiotic resistance in K. pneumoniae induced by exposure to trace antibiotic.

Effects of short-term exposure to simulated microgravity on the physiology of Bacillus subtilis and multiomic analysis.

In our study, Bacillus subtilis was disposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14 days, while the control group was disposed to the same bioreactors in a normal gravity (NG) environment for 14 days. The B. subtilis strain exposed to the SMG (labeled BSS) showed an enhanced growth ability, increased biofilm formation ability, increased sensitivity to ampicillin sulbactam and cefotaxime, and some metabolic alterations compared with the B. subtilis strain under NG conditions (labeled BSN) and the original strain of B. subtilis (labeled BSO). The differentially expressed proteins (DEPs) associated with an increased growth rate, such as DNA strand exchange activity, oxidoreductase activity, proton-transporting ATP synthase complex, and biosynthetic process, were significantly upregulated in BSS. The enhanced biofilm formation ability may be related with the DEPs of spore germination and protein processing in BSS, and differentially expressed genes involved in protein localization and peptide secretion were also significantly enriched. The results revealed that SMG may increase the level of related functional proteins by upregulating or downregulating affiliated genes to change physiological characteristics and modulate growth ability, biofilm formation ability (epsB, epsC, epsN), antibiotic sensitivity (penP) and metabolism. Our experiment may gives new ideas for the study of space microbiology.

Phenotypic, genomic, and transcriptomic changes in an Acinetobacter baumannii strain after spaceflight in China's Tiangong-2 space laboratory.

Acinetobacter baumannii is an opportunistic pathogen often found in patients with low immunity. It causes nosocomial infections, which are difficult to treat. This bacterium can rapidly mutate, developing resistance to antimicrobials and adapting to environmental stress, thereby increasing its survival. Understanding such adaptive mechanisms will be beneficial for controlling the spread of A. baumannii. Astrobiology studies have demonstrated that microbiomes from astronauts and manned spaceflight environments show resistance to stress and antibiotics. Astronauts also encounter low immunity during spaceflight missions. The extreme conditions of spaceflight provide a unique research platform for studying how opportunistic pathogens such as A. baumannii adapt to conditions such as microgravity and mutate during spaceflight. In this study, we compared phenotypic variations and analyzed genomic and transcriptomic variations in A. baumannii strains exposed to three different conditions: ST1 (64 days on Tiangong-2 space laboratory), GT1 (ground control), and Aba (original strain). Biofilm formation ability of the ST1 strain increased after 64 days of spaceflight. In addition, high-throughput sequencing revealed that some differentially expressed genes were upregulated in the ST1 strain compared to the GT1 strain. These results provide insights into the environmental adaptation of this widespread pathogen.

Decreased biofilm formation in Proteus mirabilis after short-term exposure to a simulated microgravity environment.

BACKGROUND: Microbes threaten human health in space exploration. Studies have shown that Proteus mirabilis has been found in human space habitats. In addition, the biological characteristics of P. mirabilis in space have been studied unconditionally. The simulated microgravity environment provides a platform for understanding the changes in the biological characteristics of P. mirabilis. OBJECTIVE: This study intends to explore the effect of simulated microgravity on P. mirabilis, the formation of P. mirabilis biofilm, and its related mechanism. METHODS: The strange deformable rods were cultured continuously for 14 days under microgravity simulated in high-aspect rotating vessels (HARVs). The morphology, growth rate, metabolism, and biofilm formation of the strain were measured, and the phenotypic changes of P. mirabilis were evaluated. Transcriptome sequencing was used to detect differentially expressed genes under simulated microgravity and compared with phenotype. RESULTS: The growth rate, metabolic ability, and biofilm forming ability of P. mirabilis were lower than those of normal gravity culture under the condition of simulated microgravity. Further analysis showed that the decrease of growth rate, metabolic ability, and biofilm forming ability may be caused by the downregulation of related genes (pstS, sodB, and fumC). CONCLUSION: The simulated microgravity condition enables us to explore the potential relationship between bacterial phenotype and molecular biology, thus opening up a suitable and constructive method for medical fields that have not been explored before. It provides a certain strategy for the treatment of P. mirabilis infectious diseases in space environment by exploring the microgravity of P. mirabilis.

Effects of Simulated Microgravity on the Physiology of Stenotrophomonas maltophilia and Multiomic Analysis.

Many studies have shown that the space environment plays a pivotal role in changing the characteristics of conditional pathogens, especially their pathogenicity and virulence. However, Stenotrophomonas maltophilia, a type of conditional pathogen that has shown to a gradual increase in clinical morbidity in recent years, has rarely been reported for its impact in space. In this study, S. maltophilia was exposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14days, while the control group was exposed to the same bioreactors in a normal gravity (NG) environment. Then, combined phenotypic, genomic, transcriptomic, and proteomic analyses were conducted to compare the influence of the SMG and NG on S. maltophilia. The results showed that S. maltophilia in simulated microgravity displayed an increased growth rate, enhanced biofilm formation ability, increased swimming motility, and metabolic alterations compared with those of S. maltophilia in normal gravity and the original strain of S. maltophilia. Clusters of Orthologous Groups (COG) annotation analysis indicated that the increased growth rate might be related to the upregulation of differentially expressed genes (DEGs) involved in energy metabolism and conversion, secondary metabolite biosynthesis, transport and catabolism, intracellular trafficking, secretion, and vesicular transport. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the increased motility might be associated the upregulation of differentially expressed proteins (DEPs) involved in locomotion, localization, biological adhesion, and binding, in accordance with the upregulated DEGs in cell motility according to COG classification, including pilP, pilM, flgE, flgG, and ronN. Additionally, the increased biofilm formation ability might be associated with the upregulation of DEPs involved in biofilm formation, the bacterial secretion system, biological adhesion, and cell adhesion, which were shown to be regulated by the differentially expressed genes (chpB, chpC, rpoN, pilA, pilG, pilH, and pilJ) through the integration of transcriptomic and proteomic analyses. These results suggested that simulated microgravity might increase the level of corresponding functional proteins by upregulating related genes to alter physiological characteristics and modulate growth rate, motility, biofilm formation, and metabolism. In conclusion, this study is the first general analysis of the phenotypic, genomic, transcriptomic, and proteomic changes in S. maltophilia under simulated microgravity and provides some suggestions for future studies of space microbiology.

Coulomb decay rates in monolayer doped graphene.

Excited conduction electrons, conduction holes, and valence holes in monolayer electron-doped graphene exhibit unusual Coulomb decay rates. The deexcitation processes are studied using the screened exchange energy. They might utilize the intraband and interband single-particle excitations, as well as the plasmon modes, depending on the quasiparticle states and the Fermi energies. The low-lying valence holes can decay through the undamped acoustic plasmon, so that they present very fast Coulomb deexcitations, nonmonotonous energy dependence, and anisotropic behavior. However, the low-energy conduction electrons and holes are similar to those in a two-dimensional electron gas. The higher-energy conduction states and the deeper-energy valence ones behave similarly in the available deexcitation channels and have a similar dependence of decay rate on the wave vector.

Decreased metabolism and increased tolerance to extreme environments in Staphylococcus warneri during long-term spaceflight.

Many studies have shown that the space environment can affect bacteria by causing a range of mutations. However, to date, few studies have explored the effects of long-term spaceflight (>1 month) on bacteria. In this study, a Staphylococcus warneri strain that was isolated from the Shenzhou-10 spacecraft and had experienced a spaceflight (15 days) was carried into space again. After a 64-day flight, combined phenotypic, genomic, transcriptomic, and proteomic analyses were performed to compare the influence of the two spaceflights on this bacterium. Compared with short-term spaceflight, long-term spaceflight increased the biofilm formation ability of S. warneri and the cell wall resistance to external environmental stress but reduced the sensitivity to chemical stimulation. Further analysis showed that these changes might be associated with the significantly upregulated gene expression of the phosphotransferase system, which regulates the metabolism of sugars, including glucose, mannose, fructose, and cellobiose. The mutation of S. warneri caused by the 15-day spaceflight was limited at the phenotype and gene level after cultivation on the ground. After 79 days of spaceflight, significant changes in S. warneri were observed. The phosphotransferase system of S. warneri was upregulated by long-term space stimulation, which resulted in a series of changes in the cell wall, biofilm, and chemical sensitivity, thus enhancing the resistance and adaptability of the bacterium to the external environment.

The relationship between chronic obstructive pulmonary disease and non-small cell lung cancer in the elderly.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and NSCLC often coexist and have poor prognoses, but studies investigating the impact of COPD on NSCLC have reported inconsistent findings. The objective of this study was to compare survival between NSCLC patients with and without COPD. METHODS: Medical records were retrospectively collected from 301 elderly patients pathologically diagnosed with NSCLC from the Chinese PLA General Hospital. Ultimately, a total of 200 patients were enrolled in the analysis. The survival rates between the COPD-NSCLC and non-COPD NSCLC were assessed using log-rank and Cox proportional hazard regression analyses. RESULTS: A total of 117 COPD-NSCLC and 93 non-COPD NSCLC patients were enrolled in the analysis. The median overall survival times were 108.5 months in the non-COPD group and 45.0 months in the COPD group (HR: 2.05; 95% CI, 1.36-2.97, P = 0.0004). After 118 patients underwent propensity score matching, the median overall survival times were 100.6 months in the non-COPD group and 51.9 months in the COPD group (HR: 1.59; 95% CI, 1.096-2.64, P = 0.0459). The multivariate analysis showed that presence of COPD (HR 1.619, P = 0.030), old age (HR 1.007, P < 00001), an advanced disease stage (stage Ⅲ HR 5.513, P < 0.0001; stage Ⅳ HR 11.743, P < 0.0001), the squamous cell carcinoma histological subtype (HR 3.106, P < 0.0001), the presence of a cough (HR 2.463, P = 0.001) a higher serum carcinoembryonic antigen level (HR 1.001, P = 0.023) and higher NRL (HR 2.615, P = 0.007) were independent factors that were significantly associated with poorer survival. CONCLUSION: A diagnosis of COPD had significant poorer survival outcomes in NSCLC than that of patients without COPD in this elderly population.

Genomic characterization of Escherichia coli LCT-EC001, an extremely multidrug-resistant strain with an amazing number of resistance genes.

BACKGROUND: Multidrug resistance is a growing global public health threat with far more serious consequences than generally anticipated. In this study, we investigated the antibiotic resistance and genomic traits of a clinical strain of Escherichia coli LCT-EC001. RESULTS: LCT-EC001 was resistant to 16 kinds of widely used antibiotics, including fourth-generation cephalosporins and carbapenems. In total, up to 68 determinants associated with antibiotic resistance were identified, including 8 beta-lactamase genes (notably producing ESBLs and KPCs), 31 multidrug efflux system genes, 6 outer membrane transport system genes, 4 aminoglycoside-modifying enzyme genes, 10 two-component regulatory system genes, and 9 other enzyme or transcriptional regulator genes, covering nearly all known drug-resistance mechanisms in E. coli. More than half of the resistance genes were located close to mobile genetic elements, such as plasmids, transposons, genomics islands, and insertion sequences. Phylogenetic analysis revealed that this strain may have evolved from E. coli K-12 but is a completely new MLST type. CONCLUSIONS: Antibiotic resistance was extremely severe in E. coli LCT-EC001, mainly due to mobile genetic elements that allowed the gain of a large quantity of resistance genes. The antibiotic resistance genes of E. coli LCT-EC001 can probably be transferred to other bacteria. To the best of our knowledge, this is the first report of a strain of E. coli which has such a large amount of antibiotic resistance genes. Apart from providing an E. coli reference genome with an extremely high multidrug-resistant background for future analyses, this work also offers a strategy for investigating the complement and characteristics of genes contributing to drug resistance at the whole-genome level.

Identification of potential tobramycin-resistant mutagenesis of Escherichia coli strains after spaceflight.

AIM: This study aimed to explore potential tobramycin-resistant mutagenesis of Escherichia coli strains after spaceflight. MATERIALS & METHODS: A spaceflight-induced mutagenesis of multidrug resistant E. coli strain (T1_13) on the outer space for 64 days (ST5), and a ground laboratory with the same conditions (GT5) were conducted. Both whole-genome sequencing and RNA-sequencing were performed. RESULTS: A total of 75 single nucleotide polymorphisms and 20 InDels were found to be associated with the resistance mechanism. Compared with T1_13, 1242 genes were differentially expressed in more than 20 of 38 tobramycin-resistant E. coli isolates while not in GT5. Function annotation of these single nucleotide polymorphisms/InDels related genes and differentially expressed genes was performed. CONCLUSION: This study provided clues for potential tobramycin-resistant spaceflight-induced mutagenesis of E. coli.

Increased growth rate and amikacin resistance of Salmonella enteritidis after one-month spaceflight on China's Shenzhou-11 spacecraft.

China launched the Tiangong-2 space laboratory in 2016 and will eventually build a basic space station by the early 2020s. These spaceflight missions require astronauts to stay on the space station for more than 6 months, and they inevitably carry microbes into the space environment. It is known that the space environment affects microbial behavior, including growth rate, biofilm formation, virulence, drug resistance, and metabolism. However, the mechanisms of these alternations have not been fully elucidated. Therefore, it is beneficial to monitor microorganisms for preventing infections among astronauts in a space environment. Salmonella enteritidis is a Gram-negative bacterial pathogen that commonly causes acute gastroenteritis in humans. In this study, to better understand the effects of the space environment on S. enteritidis, a S. enteritidis strain was taken into space by the Shenzhou-11 spacecraft from 17 October 2016 to 18 November 2016, and a ground simulation with similar temperature conditions was simultaneously performed as a control. It was found that the flight strain displayed an increased growth rate, enhanced amikacin resistance, and some metabolism alterations compared with the ground strain. Enrichment analysis of proteome revealed that the increased growth rate might be associated with differentially expressed proteins involved in transmembrane transport and energy production and conversion assembly. A combined transcriptome and proteome analysis showed that the amikacin resistance was due to the downregulation of the oppA gene and oligopeptide transporter protein OppA. In conclusion, this study is the first systematic analysis of the phenotypic, genomic, transcriptomic, and proteomic variations in S. enteritidis during spaceflight and will provide beneficial insights for future studies on space microbiology.

LCT-EF258 with S17I Mutation in DprA Exhibits Horizontal Gene Transfer Deficiency After Spaceflight.

BACKGROUND: Space is a special environment in which microgravity and cosmic rays are the primary factors that induce gene mutations of microorganisms. In our previous studies, a single point mutation in the gene dprA was found in an Enterococcus faecium strain of LCT-EF258 after spaceflight. DNA processing protein A (DprA) plays a prominent role in the horizontal transfer of genes among bacteria (such as Streptococcus pneumoniae, Helicobacter pylori, Bacillus subtilis, and Rhodobacter capsulatus). However, the function of DprA in E. faecium remains unknown. Furthermore, E. faecium could acquire antibiotic resistance through the horizontal transfer of antibiotic resistance genes, but it is unclear whether dprA mutants could affect this process in E. faecium.METHODS: In this study, we constructed a plasmid containing the vancomycin resistance gene vanA and then transferred the gene vanA into the dprA-mutant strain LCT-EF258 and the control strain LCT-EF90 using the electroporation technique. We then used Discovery StudioTM software to construct the 3D protein structure.RESULTS: The results showed that the horizontal transfer efficiency of the vancomycin resistance gene vanA in the dprA-mutant E. faecium decreased. And the hydrophobic core of the mutant DprA became stable and the binding affinity between the mutant DprA and ssDNA reduced.DISCUSSION: This study is an exploration of bacterial gene mutation after spaceflight. The dprA mutant could affect the ability of E. faecium to acquire exogenous resistance gene vanA, which offered us an interesting path to block the dissemination of resistance genes between strains.Yu Y, Chang D, Guo Q, Wang J, Liu C. LCT-EF258 with S171 mutation in DprA exhibits horizontal gene transfer deficiency after spaceflight. Aerosp Med Hum Perform. 2019; 90(2):116-122.

Osimertinib (AZD9291) increases radio­sensitivity in EGFR T790M non­small cell lung cancer.

Osimertinib (AZD9291) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated significant clinical benefits in patients with EGFR­sensitizing mutations or the T790M mutation. However, the potential therapeutic effect of osimertinib combined with ionizing irradiation (IR) is not well understood. The present study investigated treatment with osimertinib combined with IR in EGFR T790M non­small cell lung cancer (NCI­H1975) in vitro and in vivo. The results revealed that osimertinib inhibited proliferation and clonogenic survival following irradiation, decreased G2/M phase arrest in irradiated cells, and delayed DNA damage repair in a concentration­ and time­dependent manner. Furthermore, osimertinib alone or in combination with IR, blocked the phosphorylation of EGFR (Tyr1068/Tyr1173), protein kinase B and extracellular signal­regulated kinase. Osimertinib also enhanced the antitumor activity of IR in tumor­bearing nude mice. The results of the present study indicated that osimertinib has therapeutic potential as a radiation­sensitizer in lung cancer cells harboring the EGFR T790M mutation, providing a rationale for clinically combining osimertinib with irradiation in EGFR T790M non­small cell lung cancer.

Marinactinospora rubrisoli sp. nov., isolated from red soil.

A novel Marinactinospora strain JX35-4T was isolated from red soil which was collected from Wushan, northern Jiangxi Province, China. Analysis of the 16S rRNA gene sequences showed that strain JX35-4T belongs to the genus Marinactinospora and formed a distinct phylogenetic clade with Marinactinospora thermotolerans SCSIO 00652T and Marinactinospora endophytica YIM 690053T with sequence similarity of 96.97% and 96.42%, respectively. The strain was Gram-positive and formed branched substrate hyphae with no fragmentation, and abundant aerial hyphae that differentiated into long spore chains, and short rod-shaped spores. Growth occurred at 20-45 °C, pH 7.0-12.0 and in the presence of 0-7.5% (w/v) NaCl. The genomic DNA G + C content was determined to be 68.3 mol%. The cell wall of strain JX35-4T contained meso-diaminopimelic acid and xylose. Polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol mannosides and one unidentified phospholipid. The major fatty acids of strain JX35-4T consisted of anteiso-C17:0 and iso-C16:0. Major menaquinones were MK-9(H10), MK-12 and MK-10(H2). Based on the polyphasic data, strain JX35-4T (= CGMCC 4.7382T = DSM 104977T) is concluded to represent a novel species of the genus Marinactinospora, for which the name Marinactinospora rubrisoli sp. nov. is proposed.

Decreased biofilm formation ability of Acinetobacter baumannii after spaceflight on China's Shenzhou 11 spacecraft.

China has prepared for construction of a space station by the early 2020s. The mission will require astronauts to stay on the space station for at least 180 days. Microbes isolated from the International Space Station (ISS) have shown profound resistance to clinical antibiotics and environmental stresses. Previous studies have demonstrated that the space environment could affect microbial survival, growth, virulence, biofilms, metabolism, as well as their antibiotic-resistant phenotypes. Furthermore, several studies have reported that astronauts experience a decline in their immunity during long-duration spaceflights. Monitoring microbiomes in the ISS or the spacecraft will be beneficial for the prevention of infection among the astronauts during spaceflight. The development of a manned space program worldwide not only provides an opportunity to investigate the impact of this extreme environment on opportunistic pathogenic microbes, but also offers a unique platform to detect mutations in pathogenic bacteria. Various microorganisms have been carried on a spacecraft for academic purposes. Acinetobacter baumannii is a common multidrug-resistant bacterium often prevalent in hospitals. Variations in the ability to cope with environmental hazards increase the chances of microbial survival. Our study aimed to compare phenotypic variations and analyze genomic and transcriptomic variations in A. baumannii among three different groups: SS1 (33 days on the Shenzhou 11 spacecraft), GS1 (ground control), and Aba (reference strain). Consequently, the biofilm formation ability of the SS1 strain decreased after 33 days of spaceflight. Furthermore, high-throughput sequencing revealed that some differentially expressed genes were downregulated in the SS1 strain compared with those in the GS1 strain. In conclusion, this present study provides insights into the environmental adaptation of A. baumannii and might be useful for understanding changes in the opportunistic pathogenic microbes on our spacecraft and on China's future ISS.

Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic analyses.

BACKGROUND: Acetylsalicylic acid was renamed aspirin in 1899, and it has been widely used for its multiple biological actions. Because of the diversity of the cellular processes and diseases that aspirin reportedly affects and benefits, uncertainty remains regarding its mechanism in different biological systems. METHODS: The Drugbank and STITCH databases were used to find direct protein targets (DPTs) of aspirin. The Mentha database was used to analyze protein-protein interactions (PPIs) to find DPT-associated genes. DAVID was used for the GO and KEGG enrichment analyses. The cBio Cancer Genomics Portal database was used to mine genetic alterations and networks of aspirin-associated genes in cancer. RESULTS: Eighteen direct protein targets (DPT) and 961 DPT-associated genes were identified for aspirin. This enrichment analysis resulted in eight identified KEGG pathways that were associated with cancers. Analysis using the cBio portal indicated that aspirin might have effects on multiple tumor suppressors, such as TP53, PTEN, and RB1 and that TP53 might play a central role in aspirin-associated genes. DISCUSSION: The results not only suggest that aspirin might have anti-tumor actions against multiple cancers but could also provide new directions for further research on aspirin using a bioinformatics analysis approach.

Exploration of the involvement of LncRNA in HIV-associated encephalitis using bioinformatics.

BACKGROUND: HIV-associated encephalitis (HIVE) is one of the common complications of HIV infection, and the pathogenesis of HIVE remains unclear, while lncRNA might be involved it. In this study, we made re-annotation on the expression profiling from the HIVE study in the public database, identified the lncRNA that might be involved in HIVE, and explored the possible mechanism. METHODS: In the GEO public database, the microarray expression profile (GSE35864) of three regions of brain tissues (white matter, frontal cortex and basal ganglia brain tissues) was chosen, updated annotation was performed to construct the non-cording-RNA (ncRNA) microarray data. Morpheus was used to identify the differential expressed ncRNA, and Genbank of NCBI was used to identify lncRNAs. The StarBase, PITA and miRDB databases were used to predict the target miRNAs of lncRNA. The TargetScan, PicTar and MiRanda databases were used to predict the target genes of miRNAs. The GO and KEGG pathway analysis were used to make function analysis on the targets genes. RESULTS: Seventeen differentially expressed lncRNAs were observed in the white matter of brain tissues, for which 352 target miRNAs and 6,659 target genes were predicted. The GO function analysis indicated that the lncRNAs were mainly involved in the nuclear transcription and translation processes. The KEGG pathway analysis showed that the target genes were significantly enriched in 33 signal pathways, of which 11 were clearly related to the nervous system function. DISCUSSION: The brand-new and different microarray results can be obtained through the updated annotation of the chips, and it is feasible to identify lncRNAs from ordinary chips. The results suggest that lncRNA may be involved in the occurrence and development of HIVE, which provides a new direction for further research on the diagnosis and treatment of HIVE.

Adjuvant pegylated interferon therapy improves the survival outcomes in patients with hepatitis-related hepatocellular carcinoma after curative treatment: A meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers and the second leading cause of cancer-related deaths in men worldwide. Surgical resection of HCC remains the mainstay treatment procedure. As a result of hepatitis viral infection, the postoperative survival outcome in patients with HCC is not satisfactory. Recently, studies have reported that due to its treatment effect on hepatitis infection, pegylated interferon (Peg-IFN)-based therapy could improve the survival outcome after the treatment of hepatitis-related HCC. However, the postoperative effect of this regimen on the survival outcomes in patients with hepatitis-related HCC remains debatable. The present study conducted a meta-analysis to evaluate the effects of adjuvant Peg-IFN-based therapy on the survival outcomes in patients with hepatitis-related HCC after the curative treatment. METHODS: A systematic search was conducted to identify studies on the survival outcomes in patients with hepatitis-related HCC after a curative treatment with adjuvant Peg-IFN. PubMed, EmBase, and Cochrane Library databases were searched until September 20, 2017. The retrieved studies were independently assessed by 2 reviewers, to identify the potentially eligible studies and extract data of interest. STATA software (Version 10.0, STATA Corporation, College Station, Texas) software was used for all statistical analyses. RESULTS: The pooled results showed that adjuvant Peg-IFN-based therapy improved the 3- and 5-year recurrence-free survival (RFS) rates of patients with hepatitis-related HCC (3-year RFS, HR = 0.80; 95% CI: 0.64-0.99, P = .04; P = .81 for heterogeneity; 5-year RFS, HR = 0.82; 95% CI: 0.67-0.99, P = .04; P = .84 for heterogeneity). For the 5-year overall survival (OS) outcomes of Peg-IFN therapy for hepatitis-related HCC after the curative treatment, the pooled results showed a significant difference between the 2 groups (HR = 0.67; 95% CI: 0.47-0.97, P = .03; P = .99 for heterogeneity). CONCLUSIONS: Adjuvant Peg-IFN-based therapy could improve the RFS and OS outcomes in patients after curative treatment of hepatitis-related HCC, with no severe adverse effects.

Effects of spaceflight and simulated microgravity on microbial growth and secondary metabolism.

Spaceflight and ground-based microgravity analog experiments have suggested that microgravity can affect microbial growth and metabolism. Although the effects of microgravity and its analogs on microorganisms have been studied for more than 50 years, plausible conflicting and diverse results have frequently been reported in different experiments, especially regarding microbial growth and secondary metabolism. Until now, only the responses of a few typical microbes to microgravity have been investigated; systematic studies of the genetic and phenotypic responses of these microorganisms to microgravity in space are still insufficient due to technological and logistical hurdles. The use of different test strains and secondary metabolites in these studies appears to have caused diverse and conflicting results. Moreover, subtle changes in the extracellular microenvironments around microbial cells play a key role in the diverse responses of microbial growth and secondary metabolisms. Therefore, "indirect" effects represent a reasonable pathway to explain the occurrence of these phenomena in microorganisms. This review summarizes current knowledge on the changes in microbial growth and secondary metabolism in response to spaceflight and its analogs and discusses the diverse and conflicting results. In addition, recommendations are given for future studies on the effects of microgravity in space on microbial growth and secondary metabolism.

[Clinical characteristics and risk factors affecting outcomes of elderly patients with non-small cell lung cancer complicated by chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the clinical features, treatment strategy and risk factors affecting the prognosis of elderly patients with non-small cell lung cancer (NSCLC) complicated by chronic obstructive pulmonary disease (COPD). METHODS: We retrospectively analyzed the data of elderly patietns (>60 years) with newly diagnosed NSCLC complicated by COPD at the Geriatric Institution of General Hospital of PLA between January, 2000 and June, 2015. The clinical data collected included history of smoking, pulmonary function test results, initial treatments, TNM stage, chief complaints, comorbidities and laboratory tests. The Cox proportional hazards regression model was used to explore the prognostic factors in these patients. RESULTS: A total of 200 NSCLC patients were reviewed, of which 107 (53.5%) patients had the co-morbidity of COPD as confirmed by spirometry using bronchodilator test. The median survival of the patients with NSCLC complicated by COPD was 45.8 months with 1-, 3-, 5-, and 10-year survival rates of 80.4%, 55.4%, 41.0% and 20.0%, respectively. Stratification analysis showed that patients with COPD Gold grades 1 and 2 had a significant longer median overall survival (51.7 and 43.1 months, respectively) than those with grade 3/4 (16.9 months; P=0.020 and 0.043, respectively). Univariate and multivariate analyses using Cox proportional hazards regression model showed that an older age, a higher Gold grade, advanced disease stage (stages III and IV), squamous cell carcinoma, nonsurgical initial treatment, coughing and an elevated serum CEA level were independent risk factors for shorter survival of the patients. CONCLUSION: Multiple prognostic factors can affect the outcomes of elderly patients with NSCLC complicated by COPD, and a higher COPD Gold grade that fails to respond to treatment within 3 months is the independent risk factor for survival of the patients.