Epidemiology and risk factors of nosocomial infections in a Chinese tertiary-care hospital: a 10-year retrospective case-control study.

BACKGROUND: Nosocomial infections (NIs) are the most frequent adverse events among patients and cause a heavy burden on both health and economics. To investigate epidemiology of NIs and identify risk factors for NIs by integrating continuous long-term surveillance data. METHODS: We performed an observational study among inpatients at the Chinese People's Liberation Army General Hospital between January 1, 2010, and December 31, 2019. Infection rates, mortality rates and percentage of NIs were calculated. Trends of yearly infection rates by pathogens were assessed using Mann-Kendall trend test. Controls were matched to cases (2:1) by age (±2 years), sex, admission date (±1 year) and admission diagnosis, and conditional logistic regression was used to estimate odds ratios. RESULTS: A total of 1,534,713 inpatients were included among which 33,468 NIs cases occurred with an infection rate of 2.18%. The most common infections were respiratory system infection (52.22%), bloodstream infection (17.60%), and genitourinary system infection (15.62%). Acinetobacter. baumannii (9.6%), Klebsiella. pneumoniae (9.0%), Pseudomonas. aeruginosa (8.6%), Escherichia. coli (8.6%) and Enterococcus. faecium (5.0%) were the top five isolated pathogens. Infection rates of K. pneumoniae and carbapenems-resistant K. pneumoniae significantly increased. Prior ICU stay, surgery, any device placement (including central venous catheter, mechanical ventilation, urinary catheter, and tracheotomy), prior use of triple or more antibiotics combinations, carbapenem, and ß-Lactamase inhibitors were significantly associated with NIs. CONCLUSION: K. pneumoniae has the potential to cause a clinical crisis with increasing infection rates and carbapenem resistance. Clinical management of invasive operations and antibiotics use should be further strengthened.

Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest.

Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.

Epidemiology of healthcare-associated infections and outcomes among open and robotic pancreatoduodenectomy: A retrospective study from 2013 to 2022.

BACKGROUND AND AIM: Healthcare-associated infections (HAIs) after pancreaticoduodenectomy (PD) are one of the common postoperative complications. This study aims to investigate the epidemiology of postoperative HAIs in patients with open pancreaticoduodenectomy (OPD) and robotic pancreaticoduodenectomy (RPD). METHODS: This retrospective cohort study described the trend of HAIs in patients undergoing PD from January 2013 to December 2022 at a tertiary hospital. Patients were divided into OPD and RPD, and the HAIs and outcomes were compared. RESULTS: Among 2632 patients who underwent PD, 230 (8.7%, 95% confidence interval [CI] 7.7-9.9%) were diagnosed with HAIs, with a decreasing trend from 2013 to 2022 (P < 0.001 for trend). The incidence of postoperative HAIs was significantly higher in patients with OPD than RPD (9.6% vs 5.8%; P = 0.003). The incidence of HAIs for patients with OPD showed a decreasing trend (P = 0.001 for trend), and the trend for RPD was not significant (P = 0.554 for trend). Logistic regression showed that RPD was significantly associated with postoperative HAIs after adjusting for covariates (adjusted odds ratio = 0.654; 95% CI 0.443-0.965; P = 0.032), especially in the subgroup of patients without preoperative biliary drainage (adjusted odds ratio = 0.486; 95% CI 0.292-0.809; P = 0.006). Regarding clinical outcomes, RPD has a shorter length of stay and a more expensive charge than OPD (all P < 0.05). CONCLUSION: Postoperative HAIs in patients with PD showed a decreasing trend in recent years, especially in OPD. RPD was significantly associated with reduced postoperative HAIs and length of stay, although the charge is more expensive. Attention should be paid to postoperative HAIs in OPD, and it is imperative to continue reducing the costs of RPD.

Predicting the prognosis of lung cancer patients treated with intensity-modulated radiotherapy based on radiomic features.

AIMS: This study aimed to develop a method for predicting short-term outcomes of lung cancer patients treated with intensity-modulated radiotherapy (IMRT) using radiomic features detected through computed tomography images. METHOD: A prediction model was developed based on a dataset of radiomic features obtained from 132 patients with lung cancer receiving IMRT. Dimension reduction was performed for the features using the maximum-relevance and minimum-redundancy (mRMR) algorithm, and the least absolute shrinkage and selection operator (LASSO) regression model was utilized to optimize feature selection for the IMRT-sensitivity prediction model. The model was constructed using binary logistic regression analysis and was evaluated using the concordance index (C-index), calibration plots, receiver operating characteristic curve, and decision curve analysis. RESULTS: Fifty features were selected from 1348 radiomic features using the mRMR method. Of these, three radiomic features were selected by LASSO logistic regression to construct the radiomics nomogram. The C-index of the model was 0.776 (95% confidence interval: 0.689-0.862) and 0.791 (95% confidence interval: 0.607-0.974) in the training and validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram was clinically useful. CONCLUSION: Radiomic features have the potential to be applied to predict the short-term efficacy of IMRT in patients with inoperable lung cancer.

Susceptible-Infected-Removed Mathematical Model under Deep Learning in Hospital Infection Control of Novel Coronavirus Pneumonia.

Objective: This research aimed to explore the application of a mathematical model based on deep learning in hospital infection control of novel coronavirus (COVID-19) pneumonia. Methods: First, the epidemic data of Beijing, China, were utilized to make a definite susceptible-infected-removed (SIR) model fitting to determine the estimated value of the COVID-19 removal intensity ß, which was then used to do a determined SIR model and a stochastic SIR model fitting for the hospital. In addition, the reasonable ß and γ estimates of the hospital were determined, and the spread of the epidemic in hospital was simulated, to discuss the impact of basal reproductive number changes, isolation, vaccination, and so forth on COVID-19. Results: There was a certain gap between the fitting of SIR to the remover and the actual data. The fitting of the number of infections was accurate. The growth rate of the number of infections decreased after measures, such as isolation, were taken. The effect of herd immunity was achieved after the overall immunity reached 70.9%. Conclusion: The SIR model based on deep learning and the stochastic SIR fitting model were accurate in judging the development trend of the epidemic, which can provide basis and reference for hospital epidemic infection control.

Epidemiological Characteristics and Drug Resistance of Fungemia in General Hospitals from 2010 to 2019.

OBJECTIVE: This study intends to analyze the data of fungemia in a large tertiary hospital from 2010 to 2019, and is aimed at understanding its epidemic characteristics and drug resistance. METHODS: The "Hospital Infection Real-Time Monitoring System" was used to retrieve the case information of patients who were hospitalized for more than 48 hours from 2010 to 2019. The questionnaire was designed to collect patients' basic information, infection situation, drug resistance, and other related information. Statistical software was used for analysis. RESULTS: The fungi detection rate was in the range of 0.19%~0.75% in ten years, the average rate was 0.29%, and the rate 0.2%~0.3% since 2013, which was lower than that from 2010 to 2012. Non-Candida albicans was the main fungus, accounting for 62.50%. The drug resistance of non-C. albicans was higher than that of C. albicans, among which C. glabrata had the highest resistance rate. Data analysis showed that the patients with more serious basic diseases, combined with infection of other sites, surgery, long hospital stay, combination of antibiotics, and invasive catheterization, were more likely to occur fungemia. CONCLUSION: We should pay more attention to the patients with high-risk factors of fungemia and focus on the drug resistance of non-C. albicans, choose the right antifungal drugs, so as to improve the level of diagnosis and treatment.

A structural analytic method on the phase space data of Linac 4 MV photons based on the real world.

PURPOSE: It was given that the characteristics of the fluence distribution and the energy spectrum structure of 4MV photons on the Phase Space (PhSp) plane and a method to analyzing the characteristics. METHODS: After the PhSp file of 4 MV photons was acquired by the method of Monte Carlo (MC) calculation, the photons recorded by PhSp file were grouped based on the energy bin, and it was analyzed that the spatial distribution and energy spectrum structure of the photons. The photons in each energy group were continually grouped to sub-files according to momentum bin, and the primary and scattered photons could be separated according to the character of the fluence distribution of the photons in the sub-files. RESULTS: The energy of 4 MV beam is a continuous spectrum. The energy constituent on a pixel at different distances from the center point is different, and the average energy on the center axis of the field is the highest; The photons with 0-1.0 MeV had 42.6% of all; that with energy more than 3.0 MeV had 11.7%; greater than 4 MeV, just 1.5%. The primary and scattered photons were easy collected according to the distribution characteristics of sub-groups. CONCLUSIONS: The work to acquire and analyze the PhSp file of the 4 MV beam is significant. 4 MV, 6 MV, 8 MV, 10 MV and 15 MV energy beams basically cover the beams of radiotherapy, and a database of the energy beams could be built for the MC related research of other scholars.

Investigation and control of an outbreak of urinary tract infections caused by Burkholderia cepacian-contaminated anesthetic gel.

BACKGROUND: This report describes an outbreak of 71 patients developed B. cepacia urinary tract infection (UTI) by contaminated single-use anesthetic gel. METHODS: Epidemiological investigation of patients with B. cepacia-positive urine or blood samples between March 19, 2018 and Novemeber 15, 2018 was conducted to identify the source of infection. Microbiological samples from hospital surfaces, endoscopes, disposable items, and the hands of staff were tested for B. cepacia contamination. Pulsed-field gel electrophoresis (PFGE) was used to compare homology in B. cepacia isolates. RESULTS: During the outbreak, nosocomial B. cepacia UTI was confirmed in 71 patients. Epidemiological investigation showed that 66 patients underwent invasive urological diagnosis and treatment, while the remaining five patients underwent bedside indwelling catheterization, with all patients exposed to single-use anesthetic gel. All batches of anesthetic gel were recalled and the outbreak abated. Overall, 155 samples were collected from environmental surfaces and disposable items, and B. cepacia contamination was confirmed in samples from one used cystoscope and three anesthetic gels from the same batch. PFGE showed homology between 17 out of 20 B. cepacia isolates from patients and three isolates from the contaminated anesthetic gel. All patients achieved cure. CONCLUSION: Contaminated single-use anesthetic gel was confirmed as the source of the B. cepacia outbreak, with infection occurring during invasive urological diagnostic and treatments. Thus, investigations of nosocomial outbreaks of B. cepacia infection should consider contamination of diagnostic and treatment items used in infected patients.

Optimization of the l-tyrosine metabolic pathway in Saccharomyces cerevisiae by analyzing p-coumaric acid production.

In this study, we applied a series of genetic modifications to wild-type S. cerevisiae strain BY4741 to address the bottlenecks in the l-tyrosine pathway. A tyrosine ammonia-lyase (TAL) gene from Rhodobacter capsulatus, which can catalyze conversion of l-tyrosine into p-coumaric acid, was overexpressed to facilitate the analysis of l-tyrosine and test the strain's capability to synthesize heterologous derivatives. First, we enhanced the supply of precursors by overexpressing transaldolase gene TAL1, enolase II gene ENO2, and pentafunctional enzyme gene ARO1 resulting in a 1.55-fold increase in p-coumaric acid production. Second, feedback inhibition of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase and chorismate mutase was relieved by overexpressing the mutated feedback-resistant ARO4 K229L and ARO7 G141S , and a 3.61-fold improvement of p-coumaric acid production was obtained. Finally, formation of byproducts was decreased by deleting pyruvate decarboxylase gene PDC5 and phenylpyruvate decarboxylase gene ARO10, and p-coumaric acid production was increased 2.52-fold. The best producer-when TAL1, ENO2, ARO1, ARO4 K229L , ARO7 G141S , and TAL were overexpressed, and PDC5 and ARO10 were deleted-increased p-coumaric acid production by 14.08-fold (from 1.4 to 19.71 mg L-1). Our study provided a valuable insight into the optimization of l-tyrosine metabolic pathway.

Which Bone Marrow Sparing Strategy and Radiotherapy Technology Is Most Beneficial in Bone Marrow-Sparing Intensity Modulated Radiation Therapy for Patients With Cervical Cancer?

BACKGROUND: To evaluate the dosimetric parameters of different bone marrow sparing strategies and radiotherapy technologies and determine the optimal strategy to reduce hematologic toxicity associated with concurrent chemoradiation (cCRT) for cervical cancer. METHODS: A total of 15 patients with Federation International of Gynecology and Obsterics (FIGO) Stage IIB cervical cancer treated with cCRT were re-planned for bone marrow (BM)-sparing plans. First, we determined the optimal BM sparing strategy for intensity modulated radiotherapy (IMRT), including a BMS-IMRT plan that used total BM sparing (IMRT-BM) as the dose-volume constraint, and another plan used os coxae (OC) and lumbosacral spine (LS) sparing (IMRT-LS+OC) to compare the plan without BM-sparing (IMRT-N). Then, we determined the optimal technology for the BMS-IMRT, including fixed-field IMRT (FF-IMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). The conformity and homogeneity of PTV, exposure volume of OARs, and efficiency of radiation delivery were analyzed. RESULTS: Compared with the IMRT-N group, the average volume of BM that received ≥10, ≥20, ≥30, and ≥40 Gy decreased significantly in both two BM-sparing groups, especially in the IMRT-LS+OC group, meanwhile, two BMS-IMRT plans exhibited the similar effect on PTV coverage and other organs at risk (OARs) sparing. Among three common IMRT techniques in clinic, HT was significantly less effective than VMAT and FF-IMRT in the aspect of BM-Sparing. Additionally, VMAT exhibited more efficient radiation delivery. CONCLUSION: We recommend the use of VMAT with OC and LS as separate dose-volume constraints in cervical cancer patients aiming at reducing hematologic toxicity associated with cCRT, especially in developing countries.

Bloodstream Infection and Its Clinical Characteristics and Relevant Factors Associated with Interventional Therapy in a Large Tertiary Hospital: A Six Years Surveillance Study.

BACKGROUND: Interventional therapy has been widely used in the medical field as its advantages of minimally invasive, safe and quick recovery. Bloodstream infection (BSI) is the most common healthcare-associated infections (HAIs) after interventional therapy, but there are few reports about it. This study intends to analyze the clinical characteristics and relevant factors of BSI after six years of interventional therapy in a large tertiary teaching hospital, in order to provide guidances for the prevention and control of BSI after interventional operations. METHODS: The case information of patients with BSI after interventional therapy from 2013 to 2018 were collected through the "real-time monitoring system of healthcare-associated infections". All BSI was determined by the infection control full-time staff and clinicians. Questionnaires were designed to review case by case and register the relevant patient information into a database. A total of 18 relevant factors were counted. Statistical software was used for analysis. RESULTS: 174 cases of BSI occurred in 25401 patients, the incidence was 0.69%, and BSI accounted for 50% of all infected sites. Gram-positive bacteria accounted for 56.05%, coagulase-negative Staphylococcus was the main infectious bacteria. Relevant risk factor analysis showed that hepatocellular carcinoma, had undergone surgery, biliary complications, prophylactic antibiotic, replacement of antibiotics, number of interventional operations, days of prophylactic antibiotic use were the related risk factors associated with BSI (P < 0.05). Multivariate analysis showed that days of prophylactic antibiotic use (OR = 1.586, P < 0.05) and replacement of antibiotics (OR = 13.349, P < 0.05) were the main risk factors associated with the development of BSI. CONCLUSIONS: BSI is the main infection site after interventional surgery. For patients with the risk factors as hepatocellular carcinoma/biliary complications/had undergone surgery etc., the time of prophylactic antibiotic use can be prolonged properly before interventional surgery, and selection of single antibiotic appropriate for use could significantly aid preventive measures to avoid occurrence of BSI.

The Minimum Data Set and Quality Indicators for National Healthcare-Associated Infection Surveillance in Mainland China: Towards Precision Management.

The magnitude and scope of the healthcare-associated infections (HCAIs) burden are underestimated worldwide, and have raised public concerns for their adverse effect on patient safety. In China, HCAIs still present an unneglected challenge and economic burden in recent decades. With the purpose of reducing the HCAI prevalence and enhancing precision management, China's National Nosocomial Infection Management and Quality Control Center (NNIMQCC) had developed a Minimum Data Set (MDS) and corresponding Quality Indicators (QIs) for establishing national HCAI surveillance system, the data elements of which were repeatedly discussed, investigated, and confirmed by consensus of the expert team. The total number of data elements in MDS and QIs were 70 and 64, and they were both classified into seven categorical items. The NNIMQCC also had started two pilot projects to inspect the applicability, feasibility, and reliability of MDS. After years of hard work, more than 400 health facilities in 14 provinces have realized the importance of HCAI surveillance and contributed to developing an ability of exporting automatically standardized data to meet the requirement of MDS and participate in the regional surveillance system. Generally, the emergence of MDS and QIs in China indicates the beginning of the national HCAI surveillance based on information technology and computerized process data. The establishment of MDS aimed to use electronic health process data to ensure the data accuracy and comparability and to provide instructive and ongoing QIs to estimate and monitor the burden of HCAIs, and to evaluate the effects of interventions and direct health policy decision-making.

Overexpression of AtAGT1 promoted root growth and development during seedling establishment.

KEY MESSAGE: Arabidopsis photorespiratory gene AtAGT1 is important for the growth and development of root, the non-photosynthetic organ, and it is involved in a complex metabolic network and salt resistance. AtAGT1 in Arabidopsis encodes an aminotransferase that has a wide range of donor:acceptor combinations, including Asn:glyoxylate. Although it is one of the photorespiratory genes, its encoding protein has been suggested to function also in roots to metabolize Asn. However, experimental data are still lacking. In this study, we investigated experimentally the function of AtAGT1 in roots and our results uncovered its importance in root development during seedling establishment after seed germination. Overexpression of AtAGT1 in roots promoted both the growth of primary root and outgrowth of lateral roots. To further elucidate the molecular mechanisms underlying, amino acid content and gene expression in roots were analyzed, and results revealed that AtAGT1 is involved in a complex metabolic network and salt resistance of roots.

Peptide dendrimers G3KL and TNS18 inhibit Pseudomonas aeruginosa biofilms.

Herein we report that peptide dendrimers G3KL and TNS18, which were recently reported to control multidrug-resistant bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, strongly inhibit biofilm formation by P. aeruginosa PA14 below their minimum inhibitory concentration (MIC) value, under which conditions they also strongly affect swarming motility. Eradication of preformed biofilms, however, required concentrations above the MIC values. Scanning electron microscopy observation and confocal laser scanning micrographs showed that peptide dendrimers can destroy the biofilm morphological structure and thickness in a dose-dependent manner, even make the biofilm dispersed completely. Membrane potential analysis indicated that planktonic cells treated with peptide dendrimers presented an increase in fluorescence intensity, suggesting that cytoplasmic membrane could be the target of G3KL and TNS18 similarly to polymyxin B. RNA-seq analysis showed that the expressions of genes in the arnBCADTEF operon-regulating lipid A modification resulting in resistance to AMPs are differentially affected between these three compounds, suggesting that each compound targets the cell membrane but in different manner. Potent activity on planktonic cells and biofilms of P. aeruginosa suggests that peptide dendrimers G3KL and TNS18 are promising candidates of clinical development for treating infections.

Prospective investigation of carbapenem-resistant Klebsiella pneumonia transmission among the staff, environment and patients in five major intensive care units, Beijing.

BACKGROUND: Following the alarming outbreak of carbapenem-resistant Klebsiella pneumonia (CRKP) in five intensive care units (ICUs) of a tertiary care hospital in China, a prospective investigation of CRKP colonized/infected patients was conducted. AIM: To describe the diffusion and transmission of CRKP among epidemiologically linked ICU patients, staff and environment. METHODS: Enhanced CRKP infected/colonized case monitoring was performed by the real-time nosocomial infection surveillance system (RT-NISS). The immediate surroundings of each CRKP patient bed unit and the staff hands/gloves/gowns were sampled and then evaluated for the presence of CRKP. Antimicrobial susceptibility tests, pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) were used to identify and to characterize these isolates. FINDINGS: Among 2750 patients monitored, 67 CRKP patients were newly labeled and 11 patients' CRKP isolates were available. A total of 31.34% (21/67) bed units were positive at one or more surrounding surfaces, 7.99% (49/613) environmental samples and 3.57% (4/112) ICU staff samples were CRKP positive. The selected CRKP isolates (N = 64) exhibited intermediate to high resistance levels to the antibiotics tested apart from colistin and tigecycline. RT-NISS data combined with MLST and PFGE revealed nine likely transmission clusters. WGS analysis of these CRKP isolates revealed extensive sharing of multiple antimicrobial resistance genes and plasmid replicons among these isolates. Two carbapenemase genes blaKPC-2 (62/64) and blaOXA-48 (2/64) were identified. These CRKP isolates carried one or more plasmid replicons. CONCLUSIONS: The contamination of ICU environment and staff's hands, gloves or gowns is frequent with CRKP patients. Our study also supports the hypothesis that an association between environmental contamination and transmission of CRKP bacteria in ICUs.

Metabolic engineering strategies for improvement of ethanol production in cellulolytic Saccharomyces cerevisiae.

As a traditional ethanol-producing microorganism, Saccharomyces cerevisiae is an ideal host for consolidated bioprocessing. However, expression of heterologous cellulase increases the metabolic burden in yeast, which results in low cellulase activity and poor cellulose degradation efficiency. In this study, cellulase-expressing yeast strains that could efficiently degrade different cellulosic substrates were created by optimizing cellulase ratios through a POT1-mediated δ-integration strategy. Metabolic engineering strategies, including optimization of codon usage, promoter and signal peptide, were also included in this system. We also confirmed that heterologous cellulase expression in cellulosic yeast induced the unfolded protein response. To enhance protein folding capacity, the endoplasmic reticulum chaperone protein BiP and the disulfide isomerase Pdi1p were overexpressed, and the Golgi membrane protein Ca2+/Mn2+ ATPase Pmr1p was disrupted to decrease the glycosylation of cellulase. The resultant strain, SK18-3, could produce 5.4 g L-1 ethanol with carboxymethyl-cellulose. Strain SK12-50 achieved 4.7 g L-1 ethanol production with phosphoric acid swollen cellulose hydrolysis. When Avicel was used as the substrate, 3.8 g L-1 ethanol (75% of the theoretical maximum yield) was produced in SK13-34. This work will significantly increase our knowledge of how to engineer optimal yeast strains for biofuel production from cellulosic biomass.

Correlation between gamma passing rate and complexity of IMRT plan due to MLC position errors.

PURPOSE: This study evaluates the correlation between the susceptibility of the γ passing rate of IMRT plans to the multi-leaf collimator (MLC) position errors and a quantitative plan complexity metric. METHODS: Twenty patients were selected for this study. For each patient, two IMRT plans were generated using sliding window and step-&-shoot techniques, respectively. Modulation complexity score (MCS) was calculated for all IMRT plans, and symmetric MLC leaf bank errors, ranging from 0.3 mm to 1 mm, were introduced. Original and modified plans were delivered using Varian's Clinac iX. The obtained dose distribution using ArcCHECK was then compared with the TPS calculated dose distribution of the original plans. 3D gamma analysis was performed for each verification with passing criteria of 2%/2 mm. The γ passing rate decreasing gradient were calculated to evaluate relationship between variation of γ passing rate due to MLC errors and complexity. RESULTS: A linear regression analysis was applied between γ gradient and complexity, and the results showed a linear correlation (R2 = 0.81 and 0.82 for open and closed MLC error types, respectively) indicating the more complex plans are more susceptible to MLC leaf bank errors. Meanwhile, correlation of re-normalized γ passing rate and complexity for all errors scenarios also presented a strong correlation (r > 0.75). CONCLUSION: The statistics results revealed variation relationship of dosimetry robust of plans with various complexities to MLC errors. Our results also suggested that the observed susceptibility is independent of the delivery techniques.

Investigation of the dose perturbation effect for therapeutic beams with the presence of a 1.5 T transverse magnetic field in magnetic resonance imaging-guided radiotherapy.

BACKGROUND: Magnetic resonance imaging (MRI)-guided radiotherapy is a promising image-guided cancer radiotherapy method. For MRI-guided radiotherapy, the proper energy of a therapeutic beam is important for beam-designing processes, and the magnetic-induced dose perturbation would be mainly influenced, especially the perturbation surrounding the tissue-air or air-tissue interfaces. Thus, it was necessary to investigate the impact of beam energy from photon, proton, and carbon ion beams on the magnetic-induced dose perturbations. MATERIALS AND METHODS: Using a phantom of a water-air-water structure, the dose distributions were calculated with or without the presence of a 1.5 T uniform magnetic field through GEANT4. Based on the calculated doses, magnetic-induced dose perturbations were then obtained. For investigating the effects of beam energies on magnetic-induced dose perturbations, low-, middle-, and high-beam energies were adopted for each beam type. RESULTS AND DISCUSSION: For photon beams, the dose perturbations were increased as the beam energies increased. At the up water-air interface, the maximum perturbations exceeded 50%. Near the edge of the radiation field, perturbations of 5%-20% were achieved. For proton and carbon ion beams, their Bragg peaks were shifted from original positions, and the shifting distances were increased with the increased beam energies. However, no evident magnetic-induced dose perturbations were noted at the up water-air interface and bottom air-water interface for all the beam energies. To some extent, this study provided references for assessing the effects of beam energies on magnetic-induced dose perturbations, especially the perturbations around the air cavities inside cancer patients. CONCLUSION: In MRI-guided cancer radiotherapy, the dose perturbation effects for therapeutic beams are relatively obvious, and the beam energies of therapeutic beams have large impacts on the magnetic-induced dose perturbations with the presence of a 1.5 T transverse magnetic field.

POT1-mediated δ-integration strategy for high-copy, stable expression of heterologous proteins in Saccharomyces cerevisiae.

In biotechnological industry, increased expression cassette stability and copy number serve as important means of maintaining consistently high production levels of heterologous proteins in Saccharomyces cerevisiae. In this study, we combined δ sequences for site-specific integration with TPI1 gene from Schizosaccharomyces pombe (POT1) as a selection marker to realize high-copy integration and stable expression of heterologous proteins in S. cerevisiae. With the newly developed POT1 platform, a 32-copy integration of enhanced green fluorescent protein (EGFP) expression cassette was obtained in a single round and was stably maintained after 100 generations of growth in a rich complex medium. Talaromyces emersonii cellobiohydrolase I gene was synthesized with S. cerevisiae codon bias and expressed under the control of TPI1 promoter and terminator via POT1-mediated δ-integration; the highest specific activity yielded 238 mU g-1 of dry cell weight when p-nitrophenyl-ß-D-cellobioside was used as substrate, whereas the highest activity in cellulose hydrolysis reached 67% Avicel conversion. POT1-mediated δ-integration produces high protein levels over a wide dynamic range and enables broad applications in metabolic engineering and synthetic biology.

[Clinical value of angiogenin in predicting the prognosis of patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To explore the relationship between angiogenin-1/2 (Ang-1/2) and clinical parameters of idiopathic pulmonary fibrosis (IPF), and to assess the value of Ang-1/2 in predicting the prognosis of patients with IPF. METHODS: A retrospective analysis was conducted. Ninety-one patients diagnosed as IPF by high resolution CT (HRCT) and lung biopsy admitted to Daqing Oil Field General Hospital from March 2014 to January 2015 were enrolled. The general data, serum parameters and pulmonary function parameters of all patients were collected. After treatment, all of the 91 patients were followed-up to 2 years. The patients were divided into favorable prognosis group and unfavorable prognosis group according to follow-up results. The differences in all parameters between the two groups were compared. The relationship between Ang-1, Ang-2 and lung function parameters was analyzed by Pearson correlation analysis. Cox proportional hazard regression model was used to evaluate the effect of clinical parameters on the prognosis of patients with IPF. The effect of Ang-2 in predicting prognosis of patients with IPF was analyzed by receiver operating characteristic (ROC) curve. RESULTS: During the 2-year follow-up period, 30 of 91 patients showed a favorable prognosis, and 55 showed an unfavorable prognosis with a poor prognosis rate of 64.71%, and 6 patients withdrew from the study due to loss of follow-up and death. Compared with the favorable prognosis group, Ang-2 level in the unfavorable prognosis group was significantly increased (µg/L: 2.88±1.63 vs. 1.89±1.22, t = 2.909, P = 0.005), but Ang-1 only showed a slight increase (µg/L: 28.70±14.26 vs. 25.62±11.95, t = 1.005, P = 0.318). The results of Pearson correlation analysis showed that Ang-2 level was negatively correlated with forced expiratory volume in 1 second (FVC1) and the percentage of carbon monoxide diffusing capacity accounting for the expected value (DLCO%: r value was -0.227 and -0.206, and P value was 0.147 and 0.253, respectively), but no significant correlation between the level of Ang-1 and FVC1 as well as DLCO% was found (r value was -0.153 and -0.121, and P value was 0.147 and 0.253, respectively). Cox proportional hazard regression model analysis showed that the prognosis of patients with IPF was significantly affected by smoking time and Ang-2 (both P < 0.05), and the influence of Ang-2 was greater [relative risk (RR): 1.236 vs. 1.006, P = 0.037]. Age, gender, smoking and the levels of FVC1, DLCO% and Ang-1 had no significant effect on the prognosis of IPF patients (all P > 0.05). Prognostic analysis showed that the area under ROC curve (AUC) of Ang-2 for predicting prognosis of patients with IPF was 0.692, and the best diagnostic point was 0.35 µg/L, the sensitivity was 61.8%, the specificity was 73.3%, the positive predictive value was 69.8%, and the negative predictive value was 65.7% which indicated that Ang-2 could predict the prognosis of patients with IPF. CONCLUSIONS: Ang-2 could assess the prognosis of patients with IPF, which is expected to be used as an indicator of predicting the prognosis of patients with IPF.