A Novel Model Using Serum Thymidine Kinase 1 and Low-dose Computed Tomography Parameters to Predict Three-year Lung Cancer Risk in People with Pulmonary Nodules: A Retrospective Study.

This study was designed to develop a model of serum thymidine kinase 1 protein (STK1p) concentration in combination with low-dose computed tomography (LDCT) to predict the risk of benign pulmonary nodules progressing into lung cancer within three years in a large screening population. The study included a retrospective cohort of 6,841 individuals aged > 30 years who had LDCT-detected pulmonary nodules, but no cancer history or baseline cancer. The outcome was a lung cancer diagnosis recorded within three years after the first detection of pulmonary nodules. The adaptive least absolute shrinkage and selection operator was used to select candidate predictors and fit a logistic model. The model was validated internally by examining discrimination (area under the receiver operating characteristic curve (AUC), calibration (calibration plot)) and net benefit. A web application was developed based on the model. The results showed that the proportion of incident lung cancer cases was 0.79% (n=52). Predictors selected for the model were STK1p and three LDCT parameters (nodule size, type, and count). The AUC of the model was 0.91 (95% confidence interval (CI): 0.86, 0.96). The model had satisfactory discrimination at internal validation (AUC: 0.90 (0.84, 0.96)) and in subgroups (AUC=0.69-0.93). The high-risk group identified by the model exhibited a significantly higher three-year lung cancer risk than the low-risk group (odds ratio (OR): 66.03 (95% CI: 30.49, 162.98)). We concluded that the novel model of STK1p and LDCT parameters together can be used to accurately predict the three-year risk of lung cancer in people with pulmonary nodules.

The Photodegradation of Lignin Methoxyl C Promotes Fungal Decomposition of Lignin Aromatic C Measured with 13C-CPMAS NMR.

Solar radiation has been regarded as a driver of litter decomposition in arid and semiarid ecosystems. Photodegradation of litter organic carbon (C) depends on chemical composition and water availability. However, the chemical changes in organic C that respond to solar radiation interacting with water pulses remain unknown. To explain changes in the chemical components of litter organic C exposed to UV-B, UV-A, and photosynthetically active radiation (PAR) mediated by water pulses, we measured the chemistry of marcescent Lindera glauca leaf litter by solid-state 13C cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) over 494 days of litter decomposition with a microcosm experiment. Abiotic and biotic factors regulated litter decomposition via three pathways: first, photochemical mineralization of lignin methoxyl C rather than aromatic C exposed to UV radiation; second, the biological oxidation and leaching of cellulose O-alkyl C exposed to PAR and UV radiation interacts with water pulses; and third, the photopriming effect of UV radiation on lignin aromatic C rather than cellulose O-alkyl C under the interaction between radiation and water pulses. The robust decomposition index that explained the changes in the mass loss was the ratio of aromatic C to O-alkyl C (AR/OA) under radiation, but the ratio of hydrophobic to hydrophilic C (hydrophobicity), the carbohydrate C to methoxyl C ratio (CC/MC), and the alkyl C to O-alkyl C ratio (A/OA) under radiation were mediated by water pulses. Moreover, the photopriming effect and water availability promoted the potential activities of peroxidase and phenol oxidase associated with lignin degradation secreted by fungi. Our results suggest that direct photodegradation of lignin methoxyl C increases microbial accessibility to lignin aromatic C. Photo-oxidized compounds might be an additional C pool to regulate the stability of the soil C pool derived from plant litter by degrading lignin methoxyl and aromatic C.

Algae, shrimp grazing, and fecal pellets synergistically increase microbial activity and enhance N immobilization during Typha angustifolia leaf litter decomposition.

Algae play an important role in ecological processes of aquatic ecosystems. Understanding the interactive effects of algae with invertebrates in litter decomposition is important for predicting the effects of global change on aquatic ecosystems. We manipulated Typha angustifolia litter to control exposure to shrimp fecal pellets and/or grazing, and the green alga Chlorella vulgaris were added to test their interactive effects on T. angustifolia litter decomposition. Our results showed that algae largely shortened microbial conditioning time and improved litter palatability (increasing litter quality), resulting in greater decomposition and higher fecal pellet production. Fecal pellets enhanced grazing effects on decomposition by increasing litter ash content. The effects of algae and especially fecal pellets on decomposition were dependent on or mediated by grazing. Without grazing, algae slightly promoted decomposition and marginally offset the negative effect of fecal pellets on litter decomposition. Shrimp grazing dramatically decreased microbial activity (extracellular enzyme activity and microbial respiration) at microbial conditioning stage while enhanced microbial activity after 84 days especially with both algae and fecal pellets present. Algae significantly upregulated N- and P-acquiring and slightly downregulated C-acquiring enzyme activity. Fecal pellets significantly depressed recalcitrant C-decomposition enzyme activity. Nevertheless, the three factors synergistically and significantly increased C loss and most enzyme activities, microbial respiration, and N immobilization, resulting in the decrease of litter C:N. Our results reveal the synergistic action of different trophic levels (autotrophs, heterotrophs, and primary consumers) in the complicated nutrient pathways of litter decomposition and provide support for predicting the effects of global changes (e.g., N deposition and CO2 enrichment), which have dramatically effects on alga dynamics and on ecological processes in aquatic ecosystems.

Remediation of ABCG5-Linked Macrothrombocytopenia With Ezetimibe Therapy.

To investigate refractory hypercholesterolemia, a female patient and relatives were subjected to whole-genome sequencing. The proband was found to have compound heterozygous substitutions p. Arg446Gln and c.1118+3G>T in ABCG5, one of two genes causing sitosterolemia. When tracing these variants in the full pedigree, all maternally related heterozygotes for the intronic ABCG5 variant exhibited large platelets (over 30 fl), which segregated in an autosomal dominant manner, consistent with macrothrombocytopenia, or large platelet syndrome which may be associated with a bleeding tendency. In vitro cell-line and in vivo rat model experiments supported a pathogenic role for the variant and the macrothrombocytopenia was recapitulated in heterozygous rats and human cell lines exhibiting that single variant. Ezetimibe treatment successfully ameliorated all the symptoms of the proband with sitosterolemia and resolved the macrothrombocytopenia of the treated heterozygote relatives. Subsequently, in follow up these observations, platelet size, and size distribution were measured in 1,180 individuals; 30 were found to be clinically abnormal, three of which carried a single known pathogenic ABCG5 variant (p.Arg446Ter) and two individuals carried novel ABCG5 variants of uncertain significance. In this study, we discovered that identification of large platelets and therefore a possible macrothrombocytopenia diagnosis could easily be inadvertently missed in clinical practice due to variable instrument settings. These findings suggest that ABCG5 heterozygosity may cause macrothrombocytopenia, that Ezetimibe treatment may resolve macrothrombocytopenia in such individuals, and that increased attention to platelet size on complete blood counts can aid in the identification of candidates for ABCG5 genetic testing who might benefit from Ezetimibe treatment.

Role of serum matrix metalloproteinase in the diagnosis of gastric cancer.

OBJECTIVE: To determine the clinical value of a matrix metalloproteinase (MMP) antibody array in diagnosing gastric cancer (GC). METHODS: In this prospective study, serum samples of patients with GC (n=66) and non-neoplastic gastric disease (NGD; n=34) were collected between November 2017 and July 2018. The quantitative measurement of 10 MMP-related proteins was done using MMP arrays and compared between the two groups. RESULTS: The serum levels of MMPs 3, 8, 9 and tissue inhibitor of metalloproteinases (TIMPs) 1 and 2 were significantly higher in the GC group than in the NGD group (p<0.05). The area under curve (AUC) of the 10 MMP proteins for the diagnosis of GC varied between 0.500 and 0.658. The total AUC of all MMPs was 0.897 (95% CI: 0.837-0.957). The total AUC of the five MMPs (MMPs 3, 8, 9, and TIMPs 1 and 2) was 0.821 (95% CI: 0.733-0.909) for diagnosing GC. Also, the 10-factor and 5-factor predictive models had good diagnostic ability for early GC with an AUC of 0.865 (95% CI: 0.753-0.977) and 0.749 (95% CI: 0.600-0.898), respectively. CONCLUSIONS: The detection of multiple serum MMPs with protein biochip technology is promising to be used as a novel non-invasive tool for facilitating early diagnosis or screening of GC.

Characterization of a multidrug-resistant Klebsiella pneumoniae ST3330 clone responsible for a nosocomial outbreak in a neonatal intensive care unit.

BACKGROUND: The incidence of Klebsiella pneumonia (Kp), which has often been found to produce, extended spectrum beta-lactamase (ESBL), is rising rapidly and poses a serious risk to neonates. To date, the mechanisms related to the spread of ESBL-Kp have not been fully elucidated. This study aimed to investigate the phenotypes, genotypes, and genetic relatedness of ESBL-KP that caused an outbreak of sepsis among neonates in an intensive care unit of a Beijing hospital. METHODS: Between April 2016 and May 2018, 21 non-repetitive clinical ESBL-Kp isolates were collected from a neonatal intensive care unit (NICU) in Beijing, China and were retrospectively analyzed. Pulsed-field gel electrophoresis (PFGE) was used to analyze genetic relatedness, a VITEK 2 AST test kit was used to test antimicrobial susceptibility, sequence type (ST) was analyzed through multilocus sequence typing (MLST), and resistance genes were identified by PCR. Virulence gene profiles, biofilm formation assay, and serum killing assay were used for virulence-associated determinants. RESULTS: All strains expressed the same antibiotype, combining ESBL production, third generation cephalosporins resistance and carbapenems sensitive. Sixteen of them produced ß-lactamases (CTX-M-3 and TEM-1B), while others possessed CTX-M-15, CTX-M-24, CTX-M-66, TEM-1C, SHV-26, SHV172, and OXA-1. PFGE confirmed 5 types (A, B, C, D and E) and MLST identified a ST3330 clone (16 strains), a ST2791 clone (2 strains), a ST37 clone (1 strain), a ST34 clone (1 strain), and a ST2740 clone (1 strain). PFGE type A strains, which belong to ST3330, were identified as the main pathogens involved in the outbreak. All isolates contained virulence genes iutA and mrk. PFGE type A carried both mrk (type 3 fimbriae, biofilm formation) and fimH (type 1 fimbriae), and other STs possessed mrk. Isolates belonging to the endemic ST3330 lineage produced more biofilm than other ST isolates (median OD590 1.829 vs. 0.2280, respectively; P<0.0001). All five PFGE types isolates showed serum high sensitivity (grade 1). CONCLUSIONS: The dissemination and outbreak of ESBL-producing K. pneumoniae in this study seemed to be clonal, and the outbreak was mainly caused by ST3330 K. pneumoniae. The detection of genes (mrk and fimH) belonging to the biofilm formation may partly explain the epidemic strain has high colonization and diffusion potential.

Cardiac arrhythmias and cardiac arrest related to mushroom poisoning: A case report.

BACKGROUND: Mushroom exposure is a global health issue. The manifestations of mushroom poisoning (MP) may vary. Some species have been reported as rhabdomyolytic, hallucinogenic, or gastrointestinal poisons. Critical or even fatal MPs are mostly attributable to Amanita phalloides, with the development of severe liver or renal failure. Myocardial injury and even cases mimicking ST-segment elevation myocardial infarction (STEMI) have been previously reported, while cardiac arrhythmia or cardiac arrest is not commonly seen. CASE SUMMARY: We report a 68-year-old woman with MP who suffered from delirium, seizure, long QT syndrome on electrocardiogram (ECG), severe cardiac arrhythmias of multiple origins, and cardiac arrest. She was intubated and put on blood perfusion. Her kidney and liver functions were intact; creatine kinase-MB was mildly elevated, and then fell within normal range during her hospital stay. We sent the mushrooms she left for translation elongation factor subunit 1α, ribosomal RNA gene sequence, and internal transcribed spacer sequence analyses. There were four kinds of mushrooms identified, two of which were found to be toxic. CONCLUSION: This is the first time that we found cardiac toxicity caused by Panaeolus subbalteatus and Conocybe lactea, which were believed to be toxic to the liver, kidney, and brain. We suggest that intensive monitoring and ECG follow-up are essential to diagnose prolonged QT interval and different forms of tachycardia in MP patients, even without the development of severe liver or renal failure. The mechanisms need to be further investigated and clarified based on animal experiments and molecular signal pathways.

Quercetin improves postpartum hypogalactia in milk-deficient mice via stimulating prolactin production in pituitary gland.

Postpartum dysgalactia is a common clinical problem for lactating women. Seeking out the safe and efficient phytoestrogens will be a promising strategy for postpartum dysgalactia therapy. In this study, the postpartum mice within four groups, including control group, the model group, and the treatment groups intragastrically administrated with normal saline, bromocriptine, bromocriptine plus 17α-ethinyl estradiol, and bromocriptine plus quercetin, respectively, were used. The results showed that quercetin, a kind of natural phytoestrogen, could efficiently promote lactation yield and mammary gland development in the agalactosis mice produced by bromocriptine administration. Mechanically, quercetin, such as 17α-ethinyl estradiol, significantly stimulated prolactin (PRL) production and deposition in the mammary gland in the agalactosis mice determined by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Furthermore, quercetin could increase the expression of ß-casein, stearoyl-CoA desaturase, fatty acid synthase, and α-lactalbumin in the breast tissues that are responsible for the production of fatty acid, lactose, and galactose in the milk at the transcriptional level determined by quantitative polymerase chain reaction. Specifically, quercetin promoted primary mammary epithelial cell proliferation and stimulated prolactin receptor (PRLR) expression probably via AKT activation in vitro. In conclusion, this study indicates that estrogen-like quercetin promotes mammary gland development and lactation yield in milk-deficient mice, probably via stimulating PRL expression and release from the pituitary gland, as well as induces PRLR expression in primary mammary epithelial cells.

Paracrine signaling by VEGF-C promotes non-small cell lung cancer cell metastasis via recruitment of tumor-associated macrophages.

High expression of tumoral vascular endothelial growth factor C (VEGF-C) is correlated with clinical non-small cell lung cancer (NSCLC) metastasis and patient survival. Nevertheless, the comprehensive mechanisms accounting for VEGF-C-mediated cancer progression remain largely unclear. The present study found that VEGF-C expression was upregulated in various NSCLC cell lines. By utilizing transwell migration assay, we found that both recombinant VEGF-C protein and overexpression of VEGF-C in NSCLC cells (A549 and H441 cell lines) could efficiently enhance RAW264.7 cell (murine macrophages) migration. However, recombinant VEGF-C treatment had no effects on both CD206 (an M2 macrophage marker) expression and M1/M2 cytokine profiles of macrophages. Furthermore, additional treatment of recombinant Flt-4/Fc, the specific VEGFR-3 inhibitor or the specific VEGFR-2 inhibitor significantly suppressed macrophage migration compared with A549-CM (conditioned medium) or H441-CM alone group, confirming that NSCLC cells-derived VEGF-C is sufficient to promote macrophage migration. Interestingly, VEGF-C could stimulate the Src/p38 signaling via VEGFR-2/3 axis in macrophages, and inhibition of Src/p38 signaling obviously reversed the enhancement effect of VEGF-C on macrophage migration. Finally, the functional importance of macrophage infiltration induced by tumoral VEGF-C in promoting metastasis was established in a mouse model. In conclusion, our results highlight a novel function of tumoral VEGF-C that paracrinely induces macrophage recruitment, and resultantly promotes NSCLC cell metastasis. Therefore, VEGF-C/VEGFR-2/3 axis may be a promising microenvironmental target against progression of NSCLC.

Insight into litter decomposition driven by nutrient demands of symbiosis system through the hypha bridge of arbuscular mycorrhizal fungi.

Arbuscular mycorrhizal fungi (AMF) play an important role in litter decomposition. This study investigated how soil nutrient level affected the process. Results showed that AMF colonization had no significant effect on litter decomposition under normal soil nutrient conditions. However, litter decomposition was accelerated significantly under lower nutrient conditions. Soil microbial biomass in decomposition system was significantly increased. Especially, in moderate lower nutrient treatment (condition of half-normal soil nutrient), litters exhibited the highest decomposition rate, AMF hypha revealed the greatest density, and enzymes (especially nitrate reductase) showed the highest activities as well. Meanwhile, the immobilization of nitrogen (N) in the decomposing litter remarkably decreased. Our results suggested that the roles AMF played in ecosystem were largely affected by soil nutrient levels. At normal soil nutrient level, AMF exhibited limited effects in promoting decomposition. When soil nutrient level decreased, the promoting effect of AMF on litter decomposition began to appear, especially on N mobilization. However, under extremely low nutrient conditions, AMF showed less influence on decomposition and may even compete with decomposer microorganisms for nutrients.

Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells.

The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H2O2 enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling. Specifically, the results showed that ectopic NOX4 expression did not induce apoptosis of A549 cells; however, inhibition of Nrf2 resulted in obvious apoptotic death of NOX4-overexpressed A549 cells, accompanied by a significant increase in H2O2 level and decrease in GSH content. Besides, inhibition of Nrf2 could suppress cell growth and efficiently reverse the enhancement effect of NOX4 on cell growth. The in vivo data confirmed that inhibition of Nrf2 could interfere apoptosis resistance in NOX4-overexpressed A549 tumors and led to cell growth inhibition. In conclusion, these results reveal that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. Therefore, NOX4 and Nrf2 may be promising combination targets against malignant progression of NSCLC.

Microbiological characteristics of hypermucoviscous Klebsiella pneumoniae isolates from different body fluids.

INTRODUCTION: Reports of hypermucoviscous Klebsiella pneumoniae (hvKP) isolated from fluids other than blood or abscess are rare. The aim of the study was to compare clinical and microbiological characteristics of hvKP found in blood or abscess fluid with those isolated from other loci. METHODOLOGY: A total of 24 non-repetitive hvKP isolates were collected from January 2013 to June 2014 from patients with hvKP infections. There were 15 in Group 1 (fluid other than blood or abscess) and 9 in Group 2 (blood or abscess fluid). Medical records of all patients were reviewed. Capsular polysaccharide (CPS) typing, virulence factor determination, and multilocus sequence typing (MLST) of hvKP isolates were performed. RESULTS: Seventeen sequence types (STs) and 6 capsular serotypes were identified. Type K2CC65 was most commonly identified in Group 1 and type K2CC86 in Group 2. Deletion of pLVPK-derived loci were found in K2 and non-K1/K2 hvKP strains. Two virulent genes, fimH and ycfM, were identified more frequently in Group 2 than in Group 1. There was no difference in the frequency of other virulent genes or serotypes in the two groups. Two imipenem resistant hvKP isolates (cr-hvKP) were found in non-blood or abscess samples. CONCLUSIONS: hvKP isolated from different body fluids had similar clinical and microbiological characteristics. cr-hvKP identified in non-blood or abscess samples should raise our attention to the challenging situation and management of hvKP infection.

NOX4 supports glycolysis and promotes glutamine metabolism in non-small cell lung cancer cells.

Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and contributes to cancer progression. Nevertheless, the comprehensive mechanisms for NOX4-mediated malignant progression and oxidative resistance of cancer cells remain largely unknown. This study found that NOX4 directed glucose metabolism not only to the glycolysis but also to pentose phosphate pathway (PPP) pathway for production of NADPH in NSCLC cell lines. Besides, we also found that NOX4 promoted glutaminolysis into total GSH synthesis. Specifically, the data showed that ectopic NOX4 expression did not induce apoptosis of NSCLC cells; however, inhibition of GSH production resulted in obvious apoptotic death of NOX4-overexpressed NSCLC cells. Furthermore, we demonstrated that NOX4-induced glycolysis probably via ROS/PI3K/Akt signaling-dependent c-Myc upregulation. The selective NOX4 inhibitor, GKT137831, significantly inhibited glucose and glutamine metabolic phenotypes both in vitro and in vivo, and itself or combination with 2-DG, a synthetic glycolytic inhibitor, suppressed cancer cell growth both in vivo and in vitro. Elimination of NOX4-derived H2O2 effectively reversed NOX4 overexpression-mediated metabolic effects in NSCLC cells. NOX4 levels were significantly correlated with increased glucose and glutamine metabolism-related genes, as well as Akt phosphorylation and c-Myc expression in primary NSCLC specimens. In conclusion, these results reveal that NOX4 promotes glycolysis, contributing to NSCLC growth, and supports glutaminolysis for oxidative resistance. Therefore, NOX4 may be a promising target to reverse malignant progression of NSCLC.

Systematic Characteristic Exploration of the Chimeras Generated in Multiple Displacement Amplification through Next Generation Sequencing Data Reanalysis.

BACKGROUND: The chimeric sequences produced by phi29 DNA polymerase, which are named as chimeras, influence the performance of the multiple displacement amplification (MDA) and also increase the difficulty of sequence data process. Despite several articles have reported the existence of chimeric sequence, there was only one research focusing on the structure and generation mechanism of chimeras, and it was merely based on hundreds of chimeras found in the sequence data of E. coli genome. METHOD: We finished data mining towards a series of Next Generation Sequencing (NGS) reads which were used for whole genome haplotype assembling in a primary study. We established a bioinformatics pipeline based on subsection alignment strategy to discover all the chimeras inside and achieve their structural visualization. Then, we artificially defined two statistical indexes (the chimeric distance and the overlap length), and their regular abundance distribution helped illustrate of the structural characteristics of the chimeras. Finally we analyzed the relationship between the chimera type and the average insertion size, so that illustrate a method to decrease the proportion of wasted data in the procedure of DNA library construction. RESULTS/CONCLUSION: 131.4 Gb pair-end (PE) sequence data was reanalyzed for the chimeras. Totally, 40,259,438 read pairs (6.19%) with chimerism were discovered among 650,430,811 read pairs. The chimeric sequences are consisted of two or more parts which locate inconsecutively but adjacently on the chromosome. The chimeric distance between the locations of adjacent parts on the chromosome followed an approximate bimodal distribution ranging from 0 to over 5,000 nt, whose peak was at about 250 to 300 nt. The overlap length of adjacent parts followed an approximate Poisson distribution and revealed a peak at 6 nt. Moreover, unmapped chimeras, which were classified as the wasted data, could be reduced by properly increasing the length of the insertion segment size through a linear correlation analysis. SIGNIFICANCE: This study exhibited the profile of the phi29MDA chimeras by tens of millions of chimeric sequences, and helped understand the amplification mechanism of the phi29 DNA polymerase. Our work also illustrated the importance of NGS data reanalysis, not only for the improvement of data utilization efficiency, but also for more potential genomic information.

Clinical and molecular characteristics of multi-clone carbapenem-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in a tertiary hospital in Beijing, China.

OBJECTIVES: To provide the clinical and molecular characteristics of carbapenem-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae (cr-hvKP) in a tertiary hospital in Beijing, China. METHODS: The clinical characteristics of four patients with cr-hvKP isolates and 29 patients with carbapenem-resistant classic K. pneumoniae (cr-cKP) infections were analyzed retrospectively. The molecular characteristics of cr-hvKP and cr-cKP isolates were compared. RESULTS: The KPC-2 gene was detected in all cr-hvKPs except for cr-hvKP6. The cr-hvKPs belonged to three sequence types (STs; ST25, ST65, and ST11), with three pulsed-field gel electrophoresis patterns (I, II, and III) and two capsular serotypes (K2 and non-typeable). Although cr-hvKP1-7 did not cause invasive clinical syndromes such as community-acquired liver abscess with or without extrahepatic complications, they were all nosocomially acquired; cr-hvKP1-5 were clones disseminated between patients A and B. Compared with cr-cKPs, pLVPK-related loci, repA, iroN, and K2 capsular serotype were more prevalent in cr-hvKPs, although no significant difference was found in clinical characteristics between patients with cr-hvKP and cr-cKP infection. CONCLUSIONS: The hypervirulent ST65 and ST25K. pneumoniae, along with carbapenem-resistant clonal populations ST11, appear to have evolved into cr-hvKP strains. The evidence of bi-directional evolution and emergence of hospital-acquired multi-clone cr-hvKP indicates a confluence of virulence and carbapenem resistance, which might pose major problems in the management of K. pneumoniae infection.

[Distribution characteristics and antimicrobial resistance of pathogens about hospital infection from patients in single hematology center during 2011 and 2013].

OBJECTIVE: To analyze the characteristics of hospital infection of hematological disease, so as to provide reference for clinical therapy. METHODS: Bacterial strains and antimicrobial resistance of patients with hospital infection in Department of Hematology, Peking University Third Hospital from Jan. 2011 to Dec. 2013 were identified and analyzed retrospectively. The specimens were from their blood, urine, sputum, throat swabs and etc. RESULTS: Among the total of 168 isolates of bacteria,the majority of the bacteria strains were from sputum (42.9%); 114 (67.9%) bacteria strains were gram negative and 54 (32.1%) bacteria strains were gram positive; the pathogen testing showed that 20.8% were Pseudomonas aeruginosa,18.5% Escherichia coli,17.9% Staphylococcus aureus, 9.5% Klebsiellar pneumonia, 5.9% Staphylococcus epidermis and 27.4% other bacteria; The gram negative bacilli to cefepime, amikacin and carbapenems showed the lowest antimicrobial resistance rates, and S. aureus showed the lowest antimicrobial resistance rates to vancomycin and linezolid. CONCLUSION: Patients with hemopathy are the main population of hospital infections, the gram negative bacteria are the most common pathogens.It is very important to promptly know the change in distribution of the pathogens in order to rationally select antibiotics and reduce the incidence of bacterial infections.

Complete blood count reference intervals and age- and sex-related trends of North China Han population.

BACKGROUND: Defining common reference intervals (RIs) are encouraging. The aim of this study is to establish RIs for complete blood count (CBC) in a Chinese Han population and probe their age- and sex-related CBC trends. Additionally, we will compare the CBC RIs of Han with those of other races. METHODS: In total 1259 Han individuals (584 male and 675 female) were recruited in North China. CBC was processed on Sysmex XE-2100, Coulter LH750 and Mindray BC5800 whose traceability was well verified. The non-parametric 2.5th-97.5th percentiles RIs were calculated. RESULTS: The RIs for CBC parameters did not show apparent analyzer-specificity, apart from mean cellular volume (MCV), mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW). Red blood cell (RBC), hemoglobin (HBG), hematocrit (HCT), mean cellular hemoglobin (MCH), and mean cellular hemoglobin concentration (MGHC) are higher in males; and their male mean values tend to drop after 40 years; conversely, the female mean values tend to rise. Platelet (PLT) is higher in females and tends to drop after 40 years in both sexes. White blood cell (WBC) and absolute count of neutrophils (NE) and monocytes (MO) are higher in males, but there is no apparent change with age. Lymphocytes (LY) absolute count declines with age in males, but the same change in females is not obvious. RIs for HBG and HCT are similar among Han, Nordic, US European and US Mexican populations and are lower in US Africans. WBC RIs for Han and US African populations are lower than that for US Europeans and US Mexicans. CONCLUSIONS: RIs for major blood cell parameters are not method-dependent; variations obviously exist in age, sex and race. Consequently, common RIs for most CBC parameters appear inapplicable.

Pathological comparison of lipopolysaccharide-and graphite particle-induced acute lung injury / 中国实验动物学报

Objective To compare the differences of lung pathological changes of acute lung injury in mice in-duced by lipopolysaccharide ( LPS) and graphite particles, and to explore the possible mechanisms of acute lung injury in-duced by fine particles of different origins.Methods 140 male specific-pathogen-free Kunming mice weighing 18-20 g were randomly divided into 7 experimental groups, in addition to the normal control group.The experimental groups were treated by intratracheal instillation of LPS solution or graphite powder suspension in different doses, respectively, to induce acute lung injury in the mice.The mortality of the mice was observed, and pathological changes of the lung tissues were ex-amined by light and transmission electron microscopy.Western blot was used to detect the protein expression of neutrophil elastase ( NE) in lung tissues , and real-time quantitative PCR was used to detect mRNA expression of monocyte chemotac-tic protein-1 ( MCP-1) in the lung tissue .Results Compared with the normal control group, some pathological changes were observed in the lung tissues of the groups L ( LPS) and G ( graphite) .There were numerous macrophages in the lung tissues in the group G mice, and exudate, mainly neutrophils, in the lung tissues of the group L.The NE protein expres-sion in the lung tissue was significantly higher than that of the normal control group ( P<0.05) , and there was also a sig-nificant difference between the groups L and G (P<0.05).The MCP-1 mRNA expression in lung tissues was higher in the control group (P<0.01), and there was also a significant difference between the groups L and G (P<0.01).Conclu-sions Diverse types of particulate matters induce different pathological changes in the lungs, therefore the mechanism may also be different in the inflammatory responses.It means that the lung injuries caused by fine particles of mixed composition may have complex mechanisms.

Effect of Jinlida on cholesterol-related genes in skeletal muscle in fat-induced insulin resistance ApoE-/- mice / 中国药理学通报

Aim To investigate the effect of Jinlida on cholesterol-related genes in skeletal muscle in fat-in-duced insulin resistance ApoE-/ - mice. Methods Ten male C57 BL/6 J mice were selected as normal group ( NF );50 male ApoE-/ - mice with a high-fat feeding after 16 weeks ( HF) were divided into model group, rosiglitazone ( LGLT ) , Jinlida low dose group ( JLDL, 0. 95 g · kg-1 · d-1 ) , Jinlida medium dose group ( JLDM, 1. 9 g·kg-1 ·d-1 ) , Jinlida high dose group (JLDH, 3. 8 g·kg-1·d-1), which were per-formed intragastric administration for 8 weeks. Oil red O staining of mouse skeletal muscle was used for fat ac-cumulation. Insulin receptor ( INSR) , insulin receptor body substrate-1 ( IRS-1 ) , low-density lipoprotein re-ceptor ( LDLR ) , cholesterol sensor ( SCAP ) mRNA and protein expression in mouse skeletal muscle were measured by quantitative reverse transcription PCR ( RT-PCR ) and Western blot. Results Compared with NF group, fasting blood glucose ( FBG) , choles-terol ( TC ) , triglyceride ( TG ) and low density lipo-protein cholesterol ( LDL-C ) of HF mice were signifi-cantly elevated, while high-density lipoprotein ( HDL-C ) significantly decreased ( P < 0. 05 ) . Compared with HF group, Jinlida group could reduce to varying degrees FBG, TC, TG and LDL-C in mice, and in-crease HDL-C ( P <0. 05 ) . Jinlida could downgrade fasting serum insulin ( FINS ) level, and improve the insulin sensitive index ( ISI ) ( P < 0. 05 ) . Jinlida could obviously improve skeletal muscle fat accumula-tion of mice. Compared with NF group, skeletal mus-cle INSR, IRS-1, LDLR mRNA and protein levels of HF group were significantly decreased ( P <0. 05 ) , while SCAP mRNA and protein level increased signifi-cantly (P<0. 05). Compared with HF group, Jinlida could increase to varying degrees INSR, IRS-1, LDLR mRNA and protein levels ( P < 0. 05 ) , and lower SCAP mRNA and protein levels ( P<0. 05 ) . Conclu-sion Jinlida can alleviate fat-induced insulin resist-ance in ApoE-/ - mice through regulation of cholester-ol-related gene expression.