Ultrahigh energy storage in high-entropy ceramic capacitors with polymorphic relaxor phase.

Ultrahigh-power-density multilayer ceramic capacitors (MLCCs) are critical components in electrical and electronic systems. However, the realization of a high energy density combined with a high efficiency is a major challenge for practical applications. We propose a high-entropy design in barium titanate (BaTiO3)-based lead-free MLCCs with polymorphic relaxor phase. This strategy effectively minimizes hysteresis loss by lowering the domain-switching barriers and enhances the breakdown strength by the high atomic disorder with lattice distortion and grain refining. Benefiting from the synergistic effects, we achieved a high energy density of 20.8 joules per cubic centimeter with an ultrahigh efficiency of 97.5% in the MLCCs. This approach should be universally applicable to designing high-performance dielectrics for energy storage and other related functionalities.

5 signature genes revealed by single-cell profiling identified unique immune subtypes affecting the prognosis of ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) ranks among the most prevalent gynecological malignancies, with surgery, chemotherapy, and immunotherapy constituting primary treatment modalities. However, despite advancements, immunotherapy, particularly immune checkpoint inhibitors, has yielded suboptimal outcomes. The pressing need to identify biomarkers predictive of clinical prognosis underscores our objective. We aim to discern gene signatures and establish prognostic subgroups, specifically in the context of immunotherapy and chemotherapy, guiding clinical decision-making. MATERIALS AND METHODS: We used the Tumor Immunotherapy Gene Expression Resource (TIGER) and The Cancer Genome Atlas (TCGA) databases to extract signature genes of prognostic significance. Unsupervised consensus clustering was employed to classify patients based on these signature genes. The Tumor Immune Estimation Resource (TIMER) database, along with the R packages "maftools" and "ESTIMATE" facilitated immune infiltration estimation. Gene set variation analysis (GSVA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were implemented to probe immune-related cell signaling pathways among distinct subtypes. The Tumor Immune Dysfunction and Exclusion (TIDE) database was used to assess immunotherapy effects, while the R package "OncoPredict" evaluated drug sensitivity differences among subtypes. RESULTS: We identified five prognostically influential genes in ovarian cancer: IGFBP7, JCHAIN, CCDC80, VSIG4, and MS4A1. Utilizing these signature genes, we categorized TCGA-OV patients into five clusters, each associated with varying clinical prognoses. Notably, 2 clusters exhibited superior prognoses, accompanied by enhanced immune cell infiltration. KEGG enrichment analysis revealed their heightened enrichment in cellular immunity and immune cell interaction pathways. Given the elevated expression levels of multiple immune checkpoint molecules, these clusters may substantially benefit from immune checkpoint inhibitor therapy. Additionally, chemotherapy sensitivity analysis indicated their favorable responses to first or second-line chemotherapy regimens. CONCLUSIONS: We subclustered ovarian cancer patients by 5 signature genes obtained from the Single-cell RNA sequencing (scRNA-seq) dataset, which demonstrated a good typing effect. Patients in the two molecular subtypes showed better survival, higher immune cell infiltration, and higher drug sensitivity. This meticulous typing may help clinicians to quickly assess the prognosis of patients and the response to immunotherapy and chemotherapy.

Extracorporeal shockwave therapy of the perineum for male patients with chronic pelvic pain syndrome: a pilot study.

Background: Chronic pelvic pain syndrome (CPPS) is a complex condition that is often difficult to treat and may sometimes require a multidisciplinary team. Among the wide array of treatment options is extracorporeal shockwave therapy (ESWT). However, its role in CPPS remains controversial. The purpose of our study is to assess the efficacy and safety of ESWT of the perineum in male patients with CPPS. Methods: Fourteen patients aged between 21 and 85 years were recruited in this single-center, single-arm prospective trial from October 2018 to October 2020. ESWT was delivered to the perineum weekly for up to 8 weeks. Assessment was done via International Index for Erectile Function, International Prostate Symptom Score, King's Health Questionnaire, National Institutes of Health - Chronic Prostatitis Symptom Index, Visual Analogue Scale, Analgesic Questionnaire, and UPOINT (urinary symptoms [U], psychosocial dysfunction [P], organ-specific symptoms [O], infection-related symptoms [I], neurological/systemic conditions [N], tenderness of skeletal muscles [T]) phenotype system. The parameters are assessed before the start and end of treatment as well as at regular time points on follow-up appointments up to 20 weeks. Results: Thirteen patients completed the study. There was improvement in the Visual Analogue Scale pain score, Tenderness domain on UPOINT, King's Health Questionnaire, and National Institutes of Health - Chronic Prostatitis Symptom Index scores. In terms of erectile function, improvement in the erectile function domain of International Index for Erectile Function was observed. There was also significant improvement in lower urinary tract symptoms assessed on International Prostate Symptom Score. There were no adverse events reported post treatment and during the follow-up period. Conclusions: ESWT improved pain and quality of life of male patients with CPPS. It can be a safe and effective treatment modality in the armamentarium of CPPS.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

[EHHADH is a key gene in fatty acid metabolism pathways in hepatocellular carcinoma: a transcriptomic analysis].

OBJECTIVE: To explore the driving gene of hepatocellular carcinoma (HCC) occurrence and progression and its potential as new therapeutic target of HCC. METHODS: The transcriptome and genomic data of 858 HCC tissues and 493 adjacent tissues were obtained from TCGA, GEO, and ICGC databases. Gene Set Enrichment Analysis (GSEA) identified EHHADH (encoding enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase) as the hub gene in the significantly enriched differential pathways in HCC. The downregulation of EHHADH expression at the transcriptome level was found to correlate with TP53 mutation based on analysis of the TCGA- HCC dataset, and the mechanism by which TP53 mutation caused EHHADH downregulation was explored through correlation analysis. Analysis of the data from the Metascape database suggested that EHHADH was strongly correlated with the ferroptosis signaling pathway in HCC progression, and to verify this result, immunohistochemical staining was used to examine EHHADH expression in 30 HCC tissues and paired adjacent tissues. RESULTS: All the 3 HCC datasets showed signficnatly lowered EHHADH expression in HCC tissues as compared with the adjacent tissues (P < 0.05) with a close correlation with the degree of hepatocyte de-differentiation (P < 0.01). The somatic landscape of HCC cohort in TCGA dataset showed that HCC patients had the highest genomic TP53 mutation rate. The transcriptomic level of PPARGC1A, the upstream gene of EHHADH, was significantly downregulated in HCC patients with TP53 mutation as compared with those without the mutation (P < 0.05), and was significantly correlated with EHHADH expression level. GO and KEGG enrichment analyses showed that EHHADH expression was significantly correlated with abnormal fatty acid metabolism in HCC. The immunohistochemical results showd that the expression level of EHHADH in HCC tissues was down-regulated, and its expression level was related to the degree of hepatocytes de-differentiation and the process of ferroptosis. CONCLUSION: TP53 mutations may induce abnormal expression of PPARGC1A to cause downregulation of EHHADH expression in HCC. The low expression of EHHADH is closely associated with aggravation of de-differentiation and ferroptosis escape in HCC tissues, suggesting the potential of EHHADH as a therapeutic target for HCC.

Fluid shear stress-induced down-regulation of miR-146a-5p inhibits osteoblast apoptosis via targeting SMAD4.

Fluid shear stress (FSS) plays an important role in osteoblast apoptosis. However, the role of miRNA in osteoblast apoptosis under FSS and possible molecular mechanisms remain unknown. Our aim of the study was to explore whether miR-146a-5p regulates osteoblast apoptosis under FSS and its molecular mechanisms. FSS could down-regulate the expression of miR-146a-5p in MC3T3-E1 cells. We confirm that up-regulation of miR-146a-5p promotes osteoblasts apoptosis and down-regulation of miR-146a-5p inhibits osteoblasts apoptosis. We further demonstrated that FSS inhibits osteoblast apoptosis by down-regulated miR-146a-5p. Dual-luciferase reporter assay validated that SMAD4 is a direct target gene of miR-146a-5p. In addition, mimic-146a-5p suppressed FSS-induced up-regulation of SMAD4 protein levels, which suggests that FSS elevated SMAD4 protein expression levels via regulation miR-146a-5p. Further investigations showed that SMAD4 could inhibit osteoblast apoptosis. We demonstrated that miR-146a-5p regulates osteoblast apoptosis via targeting SMAD4. Taken together, our present study showed that FSS-induced down-regulation miR-146a-5p inhibits osteoblast apoptosis via target SMAD4. These findings may provide novel mechanisms for FSS to inhibit osteoblast apoptosis, and also may provide a potential therapeutic target for osteoporosis.

Removing the men who have sex with men blood donation deferral: Informing risk models using Canadian public health surveillance data.

OBJECTIVE: Gay, bisexual and other men who have sex with men (gbMSM) were ineligible to donate blood in most countries since the 1980's. In Canada the deferral period has been incrementally decreased from lifetime to male-to-male sex in the last 3 months. Now a few countries have removed the deferral altogether. Risk models have been utilised to estimate the probability of an HIV positive donation being released into the blood supply and to inform incremental changes to the length of the deferral period. Here we use public health data to estimate the risk of HIV if the gbMSM deferral criteria were removed in Canada. MATERIAL AND METHODS: We calculate the risk reduction among heterosexuals based on responses to standard risk questions routinely asked of donors. We assume gbMSM will donate at the same rate as heterosexual males. We apply the same risk reduction principle to HIV incidence and prevalence among gbMSM in the general population to evaluate the HIV risk without gbMSM time deferral. We model three scenarios where risk reduction is varied by assumptions about incidence and compliance with deferral criteria. RESULTS: The estimates for all scenarios were not significantly different to the currently observed scenario which predicts a residual risk of 0.02 HIV positive per million donations (95% CI: 0.000006-0.09). CONCLUSION: The models predict that removing the gbMSM deferral criteria would result in HIV residual risk similar to currently observed.

Fluid Shear Stress Promotes Osteoblast Proliferation and Suppresses Mitochondrial-Mediated Osteoblast Apoptosis Through the miR-214-3p-ATF4 Signaling Axis.

MicroRNAs (miRNAs) play vital roles in bone metabolism and participate in the mechanically induced bone alterations. The underlying molecular mechanisms by which fluid shear stress (FSS) regulate the proliferative and apoptotic phenotypic changes of osteoblasts remain elusive. The study aimed to investigate the regulatory effects of FSS on osteoblast proliferative and apoptotic phenotypes and the roles of miR-214-3p-ATF4 (activating transcription factor 4) signaling axis in the mechanomodulation processes. FSS promoted the proliferative activity of osteoblasts and suppressed mitochondrial-mediated osteoblast apoptosis. FSS decreased miR-214-3p expression and increased ATF4 expression in MC3T3-E1 osteoblasts. MiR-214-3p inhibited osteoblast proliferative activity and promoted mitochondrial-mediated osteoblast apoptosis. Overexpression of miR-214-3p attenuated FSS-enhanced osteoblast proliferation and FSS-suppressed mitochondrial-mediated osteoblast apoptosis. We validated that ATF4 acted as a target gene of miR-214-3p. Moreover, miR-214 3p regulated osteoblast proliferation and apoptosis through targeting ATF4. Taken together, our study proved that FSS could suppress mitochondrial-mediated osteoblast apoptosis and promote osteoblast proliferation through the miR-214-3p-ATF4 signaling axis.

[Risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a multicenter retrospective study].

Objective: To investigate the risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A total of 6 668 patients hospitalized for AECOPD in seven tertiary hospitals from September 2017 to January 2021 were consecutively included, and clinical data related to medical history, laboratory tests, treatment and prognosis were collected, and patients were divided into death group and survival group according to whether they died during hospitalization. After univariate analysis, multivariate logistic regression analysis was then performed to explore the independent risk factors related to in-hospital mortality. Results: Among 6 668 patients hospitalized for AECOPD, 128 patients experienced in-hospital death, with a mortality rate of 1.9%. The mean age of the death group was (81±9) years, which was significantly older than that of the survival group ((72±11) years P<0.001). The proportion of patients in the AECOPD in-hospital death group with a combination of prolonged bed rest, hypertension, myocardial infarction within 3 months, cardiac insufficiency, chronic pulmonary heart disease, pneumonia, type 2 diabetes, venous thromboembolism (VTE), and chronic renal insufficiency was also significantly higher than in the survival group (all P<0.05) The median length of stay in the in-hospital death group was 18 d, which was significantly longer than that in the survival group (9 d, P<0.001), and the proportion of patients admitted to the ICU, receiving invasive mechanical ventilation and non-invasive mechanical ventilation was also significantly higher than that in the survival group (all P<0.05). The white blood cell count, glutamic transaminase, blood creatinine, calcitoninogen, C-reactive protein, D-dimer, N-terminal B-type natriuretic and Pseudomonas aeruginosa infection rates were significantly higher than those in the survival group (all P<0.05). Multifactorial analysis showed that age>80 years (OR=3.82, 95%CI 2.36 to 6.18, P<0.001), prolonged bed rest (OR=2.95, 95%CI: 1.79 to 4.86, P<0.001), chronic pulmonary heart disease (OR=1.85, 95%CI: 1.14 to 3.00, P=0.012), and pneumonia (OR=2.75, 95%CI: 1.65 to 4.60, P<0.001), invasive mechanical ventilation (OR=7.33, 95%CI: 4.40 to 12.21, P<0.001), noninvasive mechanical ventilation (OR=3.73, 95%CI: 2.30 to 6.04, P<0.001), anemia (OR=2.03. 95%CI: 1.21 to 3.42, P=0.008), and calcitoninogen>0.5 ng/ml (OR=2.38, 95%CI: 1.41 to 4.02, P=0.001) were independent risk factors for in-hospital mortality in patients with AECOPD. Conclusion: Advanced age (>80 years), prolonged bed rest, chronic pulmonary heart disease, pneumonia, invasive mechanical ventilation, noninvasive mechanical ventilation, anemia, and calcitoninogen>0.5 ng/ml were independent risk factors for in-hospital mortality in patients hospitalized with AECOPD.

[A multicenter retrospective study on the etiology of necrotizing pneumonia in children].

Objective: To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China. Methods: A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ2 test was used for categorical variables. Results: A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ2=6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ²=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ2=4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×109/L vs. 10.5 (2.5-32.2)×109/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) µg/L vs. 0.24 (0.01-18.85) µg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions: The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

A worldwide maize panel revealed new genetic variation for cold tolerance.

KEY MESSAGE: A large association panel of 836 maize inbreds revealed a broader genetic diversity of cold tolerance, as predominantly favorable QTL with small effects were identified, indicating that genomic selection is the most promising option for breeding maize for cold tolerance. Maize (Zea mays L.) has limited cold tolerance, and breeding for cold tolerance is a noteworthy bottleneck for reaching the high potential of maize production in temperate areas. In this study, we evaluate a large panel of 836 maize inbred lines to detect genetic loci and candidate genes for cold tolerance at the germination and seedling stages. Genetic variation for cold tolerance was larger than in previous reports with moderately high heritability for most traits. We identified 187 significant single-nucleotide polymorphisms (SNPs) that were integrated into 159 quantitative trait loci (QTL) for emergence and traits related to early growth. Most of the QTL have small effects and are specific for each environment, with the majority found under control conditions. Favorable alleles are more frequent in 120 inbreds including all germplasm groups, but mainly from Minnesota and Spain. Therefore, there is a large, potentially novel, genetic variability in the germplasm groups represented by these inbred lines. Most of the candidate genes are involved in metabolic processes and intracellular membrane-bounded organelles. We expect that further evaluations of germplasm with broader genetic diversity could identify additional favorable alleles for cold tolerance. However, it is not likely that further studies will find favorable alleles with large effects for improving cold tolerance in maize.

Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells.

Induced pluripotent stem cells (iPSCs), generated from somatic cells, not only possess similar characteristics with embryonic stem cells (ESCs), but also present more advantages than ESCs in medical applications. The classical induction method that utilizes the integration of exogenous genes into chromosomes may raise the potential risk of the safety of iPSCs. To investigate the potential correlation between the integration sites of exogenous transcription factors (TFs) and iPSCs' pluripotency and safety, the integration of exogenous genes in three iPSC lines, which met the golden standard of murine developmental assay (tetraploid complementation), were analyzed. Twenty-two integration sites of exogenous TFs were identified by nested inverse polymerase chain reaction (iPCR) and 39 flanking genes' functions were analyzed by gene ontology (GO). In the 22 integrated sites, 17 (77.3%) were located in the intergenic regions and the remainder were located in introns far from the transcription start sites. Microarray analysis of the flanking genes in these cells showed that there was no distinct difference in expression levels between the iPSCs, ESCs and mouse embryonic fibroblast (MEF), suggesting that the integration of exogenous TFs has no significant influence on the expression of flanking genes. Gene ontology analysis showed that although most of the flanking genes were housekeeping genes, which were necessary for basic life activity, none of these 39 flanking genes have correlation with tumorigenesis or embryogenesis, suggesting that the integration sites hold low risk of tumorigenesis.

[Risk factors associated with mortality in patient with non-high-risk pulmonary embolism and cancer and the prognostic value of Charlson comorbidity index].

Objective: To investigate the risk factors associated with mortality and the prognostic value of Charlson comorbidity index (CCI) for mortality in patients with non-high-risk pulmonary embolism complicated by caner. Methods: Patients diagnosed with non-high-risk pulmonary embolism and caner from the medical departments of West China Hospital of Sichuan University from May, 2015 to April, 2018 were included in this study. The patients were classified into death group and survival group according to whether they died during hospitalization. Clinical information was collected and univariate along with multivariate analysis were performed in order to identify the independent risk factor related to short-term mortality in these patients. Besides, all the patients were assessed the comorbidity burden using CCI score and thereby to evaluate the prognostic value of CCI for short-time mortality. Results: A total of 195 patients were included in this study, including 115 males and 80 females. In all, 32 patients died during hospitalization and the mortality rate was 16.4%. Univariate analysis showed that male (P=0.044), age ≥65y (P=0.008), staying in bed (P=0.001), chronic pulmonary diseases (P=0.030), central venous catheterization (P=0.015), stroke history within 1 month (P=0.015), pneumonia (P=0.017), respiratory failure (P=0.017), diabetes mellitus (P=0.005) and anemia (P=0.035) were related to short term mortality of these patients. As for laboratory examination results, levels of hemoglobin and sodium in death group were significantly lower than survival group (P<0.05). Multivariate logistic regression showed that age ≥65y (OR=3.01, 95%CI: 1.05-8.68, P=0.041), staying in bed (OR=4.15, 95%CI: 1.37-12.54, P=0.012), central venous catheterization (OR=16.10, 95%CI: 2.09-124.08, P=0.008), stroke history within 1 month (OR=6.56, 95%CI: 1.05-40.95, P=0.044) and hyponatremia (OR=2.75, 95%CI: 1.06-7.15, P=0.038) were independent risk factors of short term mortality in these patients. Besides, CCI score in death group was significantly higher than that in survival group (5.66±2.96 vs 4.13±2.74, P=0.005). Pulmonary embolism patients with CCI≥4 were associated with 4.25-fold increased risk of mortality compared with patients with CCI<4 (OR=4.25, 95%CI: 1.83-9.89, P=0.001), and the per additional 1-score increase of CCI after 4 was associated with 4.89-fold increased risk of mortality (OR=4.89, 95%CI: 2.07-11.55, P<0.001). Survival analysis showed that patients with CCI≥4 had lower survival rate than the patients with CCI<4 during hospitalization (P<0.001). Conclusions: Age ≥65y, staying in bed, central venous catheterization, stroke history within 1 month and hyponatremia are independent risk factor of short-term mortality in patients with non-high-risk pulmonary embolism and caner. CCI score has prognostic value of short term mortality in these patients, and the risk increases with the increase of comorbidities patients have.

Dissecting the genetics of cold tolerance in a multiparental maize population.

KEY MESSAGE: We identify the largest amount of QTLs for cold tolerance in maize; mainly associated with photosynthetic efficiency, which opens new possibilities for genomic selection for cold tolerance in maize. Breeding for cold tolerance in maize is an important objective in temperate areas. The objective was to carry out a highly efficient study of quantitative trait loci (QTLs) for cold tolerance in maize. We evaluated 406 recombinant inbred lines from a multi-parent advanced generation intercross (MAGIC) population in a growth chamber under cold and control conditions, and in the field at early and normal sowing. We recorded cold tolerance-related traits, including the number of days from sowing to emergence, chlorophyll content and maximum quantum efficiency of photosystem II (Fv/Fm). Association mapping was based on genotyping with near one million single nucleotide polymorphism (SNP) markers. We found 858 SNPs significantly associated with all traits, most of them under cold conditions and early sowing. Most QTLs were associated with chlorophyll and Fv/Fm. Many candidate genes coincided between the current research and previous reports. These results suggest that (1) the MAGIC population is an efficient tool for identifying QTLs for cold tolerance; (2) most QTLs for cold tolerance were associated with Fv/Fm; (3) most of these QTLs were located in specific genomic regions, particularly bin 10.04; (4) the current study allows genetically improving cold tolerance with genome-wide selection.

Development of a diabetes-related nutrition knowledge questionnaire for individuals with type 2 diabetes mellitus in Singapore.

AIM: Diabetes-related nutrition knowledge (DRNK) is essential for the self-care of patients with type 2 diabetes mellitus (T2DM). A specific tool measuring DRNK can help us to understand awareness levels and tailor structured nutrition education programs. Our study aimed to develop a questionnaire to assess DRNK for individuals with T2DM in Singapore. METHODS: An expert panel was formed to consolidate in-depth, culturally suitable, and current information on DRNK. A literature review of diabetes self-care knowledge questionnaires was performed to outline the scope of the questionnaire and generate a question pool. User friendliness was tested in the first draft of the questionnaire (n = 21). Then, a second draft was tested for item difficulty, discrimination index, and internal consistency (n = 62). The final draft was examined for construct validity and test-retest reliability (n = 100). RESULTS: The final questionnaire (four sections: 27 questions) was found to be consistent and reliable. The item difficulty scores of the selected questions ranged from difficult to desirable (2-85). There was fair to good internal consistency (Cronbach's alpha: 0.66, 0.79, 0.56, and 0.78 for Sections 1, 2, 3 and 4, respectively) and construct validity (independent t-test: P < 0.001). Questions in the final questionnaire had an average discrimination index of 0.3 (reasonably good). The questionnaire was revealed to have good test-retest reliability (intraclass correlation: 0.82-0.84). CONCLUSIONS: The DRNK questionnaire is a valid and reliable measure to complement assessment tools measuring self-efficacy/behaviour in individuals with T2DM living in Singapore.

[Comparison of risk factors and short-term and long-term prognosis of pulmonary embolism between the Tibetan and Han people].

Objective: To compare the differences of risk factors and prognosis of pulmonary embolism (PE) between the Tibetans and the Hans. Methods: Patients over 18 years old with confirmed PE and complete clinical data from West China Hospital of Sichuan University from January 2010 to January 2016 were prospectively enrolled and divided into Tibetan group and Han group. Clinical data were collected to compare risk factors and short-term prognosis between Han group and Tibetan group. In addition, a 2-year follow-up was conducted among patients after discharge to investigate the long-term prognosis. Results: A total of 90 patients in Tibetan group and 626 patients in Han group were finally included in this study. Patients in Tibetan group were younger than Han group [(52.2±15.8) vs (59.8±16.6) years old, P<0.001], and the proportion of elderly patients (age ≥70 years) in Tibetan group was significantly lower than that of Han group (15.6% vs 33.7%, P=0.001). The hemoglobin, hematocrit, platelet counts and fibrinogen in Tibetan group were higher than those in Han group [(134.0±32.0) vs (122.2±25.7) g/L, (41.2±9.2)% vs (37.6±7.3)% and (222.2±97.5)×10(9)/L vs (187.5±87.2)×10(9)/L, 3.71(2.51, 4.89) vs 3.31(2.44, 4.42) g/L; P<0.001, <0.001 and P=0.001, 0.048, respectively]. Malignancy and chronic obstructive pulmonary disease were more common in Han group (P=0.011, 0.001), while prior venous thromboembolism history, pregnancy or a history delivery within 1 month were more common in Tibetan group (P=0.041, 0.001). Both short-term and long-term mortality in Tibetan group were significantly lower than that in Han group (2.2% vs 11.5%, 13.6% vs 24.9%; P=0.005, 0.020). Conclusions: Hypercoagulable state plays an important role in the pathogenesis of PE in Tibetan patients. Both short-term and long-term prognosis of PE in Tibetan patients are better than that in Han patients.

3,5-Dicaffeoylquinic Acid Disperses Aspergillus Fumigatus Biofilm and Enhances Fungicidal Efficacy of Voriconazole and Amphotericin B.

BACKGROUND The aim of this study was to evaluate the dispersal effects of 3,5-dicaffeoylquinic acid (3,5-DCQA) against the preformed biofilm of Aspergillus fumigatus and to investigate its potential mechanism. MATERIAL AND METHODS Aspergillus fumigatus biofilms of laboratory strain AF293 and clinical strain GXMU04 were generated in 24- or 96-well polystyrene microtiter plates in vitro. Crystal violet assay and XTT reduction assay were performed to evaluate the effects of 3,5-DCQA on biofilm biomass, extracellular matrix, and metabolic activity alteration of cells in biofilms. Real-time PCR was performed to quantify the expression of hydrophobin genes. The cytotoxicity of 3,5-DCQA on human erythrocytes was evaluated by a hemolytic assay. RESULTS The results indicated that 3,5-DCQA in subminimum inhibitory concentrations (256 to 1024 mg/L) elicited optimal A. fumigatus biofilm dispersion activity and improved the efficacy of VRC and AMB in minimal fungicidal concentrations (MFCs) to combat fungal cells embedded in biofilms. The results of scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM) revealed 3,5-DCQA facilitated the entry of antifungal agents into the A. fumigatus biofilm through eliminating the hydrophobic extracellular matrix (ECM) without affecting fungal growth. Real-time PCR indicated that 3,5-DCQA down-regulated the expression of hydrophobin genes. Hemolytic assay confirmed that 3,5-DCQA exhibited a low cytotoxicity against human erythrocytes. CONCLUSIONS Subminimum inhibitory concentrations of 3,5-DCQA can disperse A. fumigatus biofilm and enhance fungicidal efficacy of VRC and AMB through down-regulating expression of the hydrophobin genes. The study indicated the anti-biofilm potential of 3,5-DCQA for the management of A. fumigatus biofilm-associated infection.

Simultaneous determination of organochlorine and pyrethriod pesticide residues in the Chinese patent medicines by gas chromatography-tandem mass spectrometry.

A simple, sensitive, reliable method was developed for the simultaneous determination of organochlorine and pyrethriod pesticide residues in Chinese patent medicines Six ingredient rehmannia pills and Xiaoyao pills. These pesticides were extracted by ethyl acetate. The extraction time and volume of ethyl acetate were optimized. Cleanup of extracts was performed with dispersive-solid phase extraction using graphitized carbon black as the sorbent. The determination of pesticides in the final extracts was carried out by gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode (GC-MS/MS, MRM). The linearity of the calibration curves is good in matrix-matched standard and yields the coefficients of determination (R2) ≥0.99 for all of the target analytes. Under optimized conditions, the average recoveries (five replicates) for most pesticides range from 75.5% to 114.6%, and RSDs are less than 10.0%. The LODs of 18 pesticides in Six ingredient rehmannia pill and Xiaoyao pills are in the range of 0.01-8.82 µg kg-1. The developed method meets the requirements of pesticide residue analysis and could be effectively used for routine analysis of the organochlorine and pyrethriod pesticide residues in Six ingredient rehmannia pills and Xiaoyao pills.