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Background: Data on treatable traits (TTs) in different populations are limited., Objective: To assess TTs in elderly patients with asthma and compare them to younger patients, to evaluate the association of TTs with future exacerbations, and to develop an exacerbation prediction model., Methods: We consecutively recruited 521 participants at West China Hospital, Sichuan University based on the Australasian Severe Asthma Network, classified as elderly (n = 62) and nonelderly (n = 459). Participants underwent a multidimensional assessment to characterize the TTs and were then followed up for 12 months. TTs and their relationship with future exacerbations were described. Based on the TTs and asthma control levels, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort., Results: A total of 38 TTs were assessed. Elderly patients with asthma had more chronic metabolic diseases, fixed airflow limitation, emphysema, and neutrophilic inflammation, whereas nonelderly patients with asthma exhibited more allergic characteristics and psychiatric diseases. Nine traits were associated with increased future exacerbations, of which exacerbation prone, upper respiratory infection-induced asthma attack, cardiovascular disease, diabetes, and depression were the strongest. A model including exacerbation prone, psychiatric disease, cardiovascular disease, upper respiratory infection-induced asthma attack, noneosinophilic inflammation, cachexia, food allergy, and asthma control was developed to predict exacerbation risk and showed good performance., Conclusions: TTs can be systematically assessed in elderly patients with asthma, some of which are associated with future exacerbations, proving their clinical utility of evaluating them. A model based on TTs can be used to predict exacerbation risk in people with asthma., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Upper tract urothelial carcinoma (UTUC) is a rare tumor with an incidence that varies greatly between Eastern and Western countries. Transaldolase 1 (TALDO1) is a rate-limiting enzyme of the pentose phosphate pathway. In humans, aberrant TALDO1 activity has been implicated in various autoimmune diseases and malignancies; however, the function of TALDO1 in UTUC has not been previously investigated. Here we evaluated the clinical significance of TALDO1 expression in 115 paraffin-embedded tumor samples from patients with UTUC using immunohistochemistry. Our results demonstrated that there was an association between high TALDO1 expression and advanced stage (P = 0.011), tumor size (P = 0.005), tumor location (P = 0.047), distant metastases (P = 0.023), local recurrence (P = 0.002), and cancer death (P = 0.003). Using univariate and multivariate analyses, we found that chemotherapy was an independent factor for bladder recurrence-free survival. Late stage (III/IV) and high TALDO1 expression were independent prognostic factors for progression-free and cancer-specific survival. In summary, increased TALDO1 expression in UTUC was significantly correlated with late stage, tumor size, tumor location, distant metastases, local recurrence, and cancer death. Therefore, high TALDO1 expression could be a predictor of poor survival in patients with UTUC. Further studies are necessary to investigate the role of TALDO1 in UTUC development., (© 2021 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

The importance of blood cell markers in patients with malignant tumors has been studied, but there are few studies on the prognostic value of hemoglobin-to-red cell distribution width ratio (HRR) in cancer. This is the first study to investigate the effect of preoperative HRR on patients with upper tract urothelial carcinoma (UTUC). Our retrospective cohort study included 730 UTUC patients who underwent nephroureterectomy from 2000 to 2019. Clinicopathological parameters were compared according to HRR levels, and the relationship between blood cell markers (HRR, white blood cell [WBC] count, platelet count) and prognosis was evaluated using Kaplan-Meier method and Cox regression model. We found that patients with HRR ≤ 1.05 tended to have worse renal function, higher pathological stages, and more high-grade tumors. In univariate analysis, HRR ≤ 1.05, WBC > 8.65 × 10 3 cells/μL and platelets >309 × 10 3 cells/μL were associated with poor progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Multivariate analysis demonstrated that HRR ≤ 1.05 and WBC > 8.65 × 10 3 cells/μL were independent prognostic factors for predicting deterioration of PFS, CSS, and OS. In conclusion, HRR and WBC are easy to obtain in clinical practice and are useful indicators to provide prognostic information before surgery for UTUC.

Urothelial carcinoma (UC) of the upper tract (UTUC) and urinary bladder (UBUC) is a heterogeneous malignancy. Through transcriptomic profiling of the Gene Expression Omnibus UBUC dataset (GSE31684), we discovered that epidermal growth factor-containing fibulin-like extracellularmatrix protein 1 ( EFEMP1 ) was the most upregulated gene during metastatic development. EFEMP1 is an important component of basement membranes and acts as an enzyme regulator in extracellular matrix biology. Initially, evaluation of EFEMP1 mRNA expression in 50 UBUCs showed significantly upregulated levels in high stage UC. We further validated the clinical significance of EFEMP1 in 340 UTUC and 295 UBUC using immunohistochemistry, evaluated by H-score. High EFEMP1 immunoexpression significantly correlated with high pathologic stage, high histological grade, lymph node metastasis, vascular invasion, perineural invasion and high mitosis (all p < 0.05). After adjusting for established clinicopathological factors, EFEMP1 expression status retained its prognostic impact on disease-specific survival and metastasis-free survival in UTUC and UBUC (all p < 0.01). Furthermore, Ingenuity Pathway Analysis showed that actin cytoskeleton signaling, tumor microenvironment pathway and mitochondrial dysfunction were significantly enriched by EFEMP1 dysregulation. In conclusion, high EFEMP1 expression was associated with adverse pathological features in UC and independently predicted worse outcomes, suggesting its roles in clinical decision-making and risk stratification.

Background: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China., Methods: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG&#95;012247.2 (NM&#95;014251.3): c.852&#95;855del, c.1638&#95;1660dup, c.615+5G>A, and c.1751-5&#95;1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests., Results: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ 2 =8.570, P=0.003) in general, with higher c.852&#95;855del (54/6,818 vs. 13/5,492, χ 2 =17.328, P=0.000) but lower c.1751-5&#95;1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638&#95;1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly., Conclusions: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tp-21-58). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Background: Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts-eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma, and paucigranulocytic asthma (PGA). Although research has focused on EA and NA, there is little known about PGA., Objective: To study the heterogeneity of PGA and identify possible PGA clusters to guide clinical treatment., Methods: Patients with PGA were grouped by hierarchical cluster analysis and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability., Results: Cluster analysis of 145 patients with PGA identified 3 clusters: cluster 1 (n = 110, 75.9%) was "mild PGA," cluster 2 (n = 20, 13.8%) was "PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases," and cluster 3 (n = 15, 10.3%) was "smoking-associated PGA." Cluster 3 had significantly increased risk of severe exacerbation (relative risk [RR] = 6.43, P = .01), emergency visit (RR = 8.61, P = .03), and hospitalization (RR = 12.94, P < .01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time., Conclusions: Among 3 identified PGA clusters, cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: High breast density is significantly associated with an increased risk of breast diseases. Presently, suspected breast masses assessed as Breast Imaging-Reporting and Data System (BI-RADS) grade 4 provide a wide range of positive predictive values. Moreover, subcategories (4a, 4b, and 4c) are still under consideration as the diagnostic criteria are neither comprehensive nor objective. However, whether mammography breast density (MBD) has any impact on the accurate grading of BI-RADS 4 assessed by ultrasound (US) remains unknown., Methods: A total of 1,086 women with 1,293 breast masses were included and assessed as BI-RADS 3-5 by US. The subcategories of MBD (from the ACR-a to the ACR-d group) were assessed by mammography according to the criteria of the American College of Radiology (ACR). The clinicopathological characteristics of these patients were reviewed retrospectively. The malignancy rates of breast masses among different subgroups assessed by BI-RADS were re-estimated with MBD., Results: Almost all BI-RADS 3 masses were classified as benign and nearly all BI-RADS 5 masses were identified as malignant. Significant inverse associations between MBD and malignancy rates were detected between the BI-RADS 4a and BI-RADS 4b groups. Moreover, malignancy rates decreased significantly from ACR-a to ACR-d for BI-RADS 4a and 4b breast lesions (P<0.001). However, this trend was not observed in BI-RADS 4c breast lesions., Conclusions: MBD could serve as a crucial factor for the accurate grading of BI-RADS 4 lesions assessed by US. We strongly recommend the adoption of the MBD as a possible supplemental screening modality for US. Furthermore, it is equally beneficial for accurate risk assessment and screening recommendations based on MBD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-313). Ting Xu reports that she is from Shenzhen Mindray Biomedical Electronics Co., Ltd. The other authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Background: We aimed to identify prognostic biomarkers of upper tract urothelial carcinomas (UTUCs), including microRNAs (miRNAs) and genes which account for only 5% to 10% of all urothelial carcinomas (UCs). In Taiwan, this figure is markedly higher, where it can reach up to 30% of UC cases., Materials and Methods: Using next-generation sequencing (NGS), we analyzed two pairs of renal pelvis tumors and adjacent normal urothelial tissues to screen miRNAs and messenger RNAs. By combining bioinformatics analysis from miRmap, Gene Expression Omnibus (GEO), and Oncomine and Ingenuity ®  Pathway Analysis databases, we identified candidate genes. To search for upstream miRNAs with exact target binding sites, we used miRmap, TargetScan, and miRDB to enforce evidence. Then, we clarified gene and protein expression through an in vitro study using western blot analysis and quantitative real-time reverse transcriptase-PCR., Results: Interactions between selected target genes obtained using the NGS and miRmap methods were assessed through a Venn diagram analysis. Six potential genes, namely, PDE5A, RECK, ZEB2, NCALD, PLCXD3 and CYBRD1 showed significant differences. Further analysis of gene expression from the GEO dataset indicated lower expression of PDE5A, RECK, ZEB2, and CYBRD1 in bladder cancer tissue than in normal bladder mucosa, which indicated that PDE5A, RECK, ZEB2, and CYBRD1 may act as tumor suppressors in UTUC. In addition, we compared the expression of these genes in various UC cell lines (RT4, BFTC905, J82, T24, UMUC3, 5637, BFTC 909, UMUC14) and found decreased expression of PDE5A in muscle-invasive UC cells compared with the RT4 cell line. Furthermore, by using paired UTUC and normal tissues from 20 patients, lower PDE5A expression was also demonstrated in tumor specimens., Conclusions: Our findings suggest these candidate genes may play some roles in UTUC progression. We propose that these markers may be potential targets clarified by in vitro and in vivo experiments. PDE5A also potentially presents tumor suppressor genes, as identified by comparing the expression between normal and tumor specimens., Competing Interests: The authors declare there are no competing interests., (©2021 Lee et al.)

A novel Gram-strain-negative, rod-shaped, non-flagellated, non-gliding, beige-pigmented and aerobic bacterium, designated strain UJN715 T , was isolated from rhizosphere soil of Alhagi sparsifolia obtained from Alear city, located in Xinjiang province, PR China. Growth optimally occurred at 37 °C, pH 6.5-7.5, and 0-3% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain UJN715 T belonged to the genus Chelativorans, with the highest sequence similarity to Chelativorans multitrophicus DSM 9103  T (97.7%). Genome sequencing revealed a genome size of 5 702 301 bp and a G + C content of 64.1 mol%. The ANI, POCP and the dDDH between strain UJN715 T and C. multitrophicus DSM 9103  T were 76.2%, 49.3%, and 20.5%, respectively. The prediction result of secondary metabolites based on genome showed that the strain UJN715 T contained one cluster of ectoine production, one cluster of non-ribosomal peptide synthetase (NRPS), one cluster of type I polyketide synthases (TIPKS), one cluster of bacteriocin, one cluster of TfuA-related, one cluster of N-acetylglutaminylglutamine amide (NAGGN) production, one cluster of terpene production, two clusters of homoserine lactone (Hserlactone) production. The major respiratory quinone was Q-10. The major fatty acids were iso-C 17:0 , C 18:0 and C 19:0 cyclo ω8c and its polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phospholipids, unknown lipids, diphosphatidylglycerol, aminoglycolipid, unidentified aminophospholipids. On the basis of these data, strain UJN715 T is considered to represent a novel species of the genus Chelativorans, for which the name Chelativorans alearense sp. nov. is proposed. The type strain is UJN715 T (= KCTC 72856 T  = CCTCC AB2019378 T ).

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (M pro ) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing M pro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 M pro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of M pro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To investigate the safety and efficacy of enhanced recovery after surgery (ERAS) in the clinical management of hypopharyngeal squamous cell carcinoma (HSCC). Methods: In this retrospective study, a total of 168 patients with pyriform sinus carcinoma in Qilu Hospital of Shandong University from January 2015 to January 2019 were divided into two groups, based on the different perioperative interventions that patients received, i.e. the ERAS group ( n= 64) and the conventional group ( n= 104), including 164 males and 4 females, whose ages ranged from 42 to 84 years old. The difference between two groups in the operative time, postoperative nutritional status, incidences of postoperative complications and postoperative hospitalization time were compared using the student's t test, Chi-squared test or Fisher's exact test. Results: Compared with the conventional group, patients in the ERAS group had significantly shorter operative time [(166.8±58.2) min vs. (183.3±39.9) min, t =-2.72, P= 0.031], higher levels of postoperative serum albumin [(38.3±4.2) μmol/L vs. (36.6±3.3) μmol/L, t =2.73, P= 0.007] and more body weight [(65.4±9.4) kg vs. (62.1±9.4) kg, t =2.22, P= 0.028], lower incidences of postoperative subcutaneous infection [7.8% (5/64) vs. 20.2% (21/104), χ²= 4.64, P =0.03] and severe pneumonia [4.7% (3/64) vs. 15.4% (16/104), χ²= 4.52, P =0.03], and shorter postoperative hospitalization time [(16.5±3.9) d vs. (18.2±4.3) d, t =-2.65, P <0.05]. Conclusion: ERAS is effective and safe in the surgical management of HSCC, with benefits in reducing the operative stress via saving operation time, shortening the hospitalization time, ameliorating nutritional status and decreasing the incidences of complications.

A novel Gram-strain-negative, beige-pigmented, aerobic, rod-shaped, non-flagellated and non-gliding bacterium, designated strain lm93 T , was isolated from rhizosphere soil of Alhagi sparsifolia obtained from Alar city, located in Xinjiang province, China. Growth optimally occurred at 30 °C, pH 6.5-7.5, and 0-2% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain lm93 T belonged to the genus Chelativorans, with highest sequence similarity to Chelativorans multitrophicus DSM 9103 T (96.9%). Genome sequencing revealed a genome size of 5 689 708 bp and a G + C content of 64.3 mol%. The ANI, POCP and the dDDH between strain lm93 T and C. multitrophicus DSM 9103 T were 76.4%, 54.8% and 0.8%, respectively. The prediction result of secondary metabolites based on genome showed that the strain lm93 T contained one cluster of bacteriocin, one cluster of terpene production, two clusters of ectoine production, one cluster of non-ribosomal peptide synthetase, one cluster of type I polyketide synthases, three clusters of homoserine lactone production, one cluster of N-acetylglutaminylglutamine amide production and one cluster of phosphonate production. The major respiratory quinone was Q-10. The major fatty acids were C 19:0 cyclo ω8c, iso-C 17:0 and summed feature 8 (C 18:1 ω6c and/or C 18:1 ω7c) and its polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified aminophospholipids, aminoglycolipid, three unknown lipids and diphosphatidylglycerol. On the basis of these data, strain lm93 T is considered to represent a novel species of the genus Chelativorans, for which the name Chelativorans xinjiangense sp. nov. is proposed. The type strain is lm93 T (= KCTC 72857 T  = CCTCC AB2019376 T ).

Purpose: The metabolic syndrome was associated with bladder cancer in the previous studies. However, there have no large-scale cohort studies to elucidate the relationship between metabolic syndromes and urothelial carcinoma including urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC)., Methods: We analyze a population-based cohort study by using physical examination data and diagnosis of UC from the Taiwan Cancer Registry Database. Differences in demographic and clinical characteristics among UTUC and non-UTUC groups, UBUC and non-UBUC groups were compared. Odds ratios (ORs) for determining risk factors were estimated through the multiple logistic regression model., Results: A total of 557,063 records for 211,319 participants which consisted of 31 UTUC and 309 UBUC met the eligibility criteria in this study. Our results showed that female are more likely to develop UTUC than male. As opposed to UTUC, male are more likely to develop UBUC than female. It also showed that participants smoked or chewed betel quid daily are more likely to develop UBUC. Age and estimated glomerular filtration rate (eGFR) are significantly increased the risk of developing UTUC. The association between the eGFR and risk of UTUC is stronger (P < 0.001) for eGFR < 45 (vs. eGFR ≥ 75, OR = 6.795; 95% CI 2.901-15.917). Metabolic syndrome is related to higher risk of UBUC incidence [OR was 1.373 (95% CI 1.104-1.707)]., Conclusions: There was a significant relationship between the incidence of UBUC and metabolic syndrome. Renal function impairment presents higher risk in both UBUC and UTUC development.

Background: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic., Methods: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes., Results: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64)., Conclusions: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

As all- trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority ( P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups ( P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297)., Competing Interests: The authors declare no competing interest.

Background: Hospitalization due to acute asthma exacerbation (AE) is a highly detrimental situation requiring critical management to prevent further deterioration, including mechanical ventilation, intensive care unit (ICU) admission, and death. However, patients hospitalized for AEs are highly heterogeneous and remain largely unexplored., Objective: To identify clinical and inflammatory phenotypes of AE requiring hospitalization associated with in-hospital outcomes., Methods: We performed a hierarchical cluster analysis of 825 consecutively recruited patients hospitalized for AEs. Logistic regressions were conducted to quantify the independent associations of the identified phenotypes with in-hospital outcomes. Decision tree analysis was developed to predict cluster assignment., Results: We identified 3 clusters of patients, which had significantly different characteristics associated with in-hospital adverse outcomes. Cluster 1 (n = 526, 63.8%) was a late-onset phenotype, cluster 2 (n = 97, 11.8%) was an early-onset phenotype, and cluster 3 (n = 202, 24.5%) was a phenotype with fewer eosinophils and more comorbidities. Clusters 2 and 3 had an elevated risk of death (relative ratio [RR adj ], 18.10 and 19.17, respectively) and mechanical ventilation (RR adj , 2.56 and 5.71, respectively) than did cluster 1. Individuals in cluster 3 had an extended length of hospital stay (11 days), increased hospitalization direct costs (13,481.57 Chinese Yuan), and a higher risk of ICU admission (RR adj , 2.14) than individuals in clusters 1 and 2. The decision tree assigned 90.8% of the participants correctly., Conclusions: We identified 3 phenotypes with differential clinical and inflammatory characteristics associated with in-hospital adverse outcomes. These new phenotypes might have important and clinically relevant implications for the management of patients hospitalized for AEs., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The trachea is the uppermost respiratory airway element connecting the larynx to the bronchi Airway reconstructions in humans are often developed from animal models but there is limited knowledge comparing tracheal biomechanics between species. We aimed to assess the structure and biomechanics of porcine, canine, caprine and human airways., Methods: Tracheas from pigs (n=15), goats (n=9) and canines (n=9) were divided into three groups (4, 6 and 8-ringswhile human left principal brochi (n=12) were divided into two groups (3and-rings). Airway structures were compared using histology and scanning electron microscopy. Biomechanical properties were measured subjecting samples to uniaxial tension and compression, recording the elastic modulus and (tensile and compressive) strengths., Results: The structures of animal tracheal and human bronchia appeared similar. Biomechanical testing revealed that the elastic modulus of 8-ring tracheas was 1,190.48±363.68, 2,572.00±608.19 and 1,771.27±145.54 kPa, for porcine, canine and caprine samples, respectively, while corresponding tensile strengths were 437.63±191.41, 808.38±223.48 and 445.76±44.00 kPa. Comparable measures of anterior-posterior (A-P) compression strengths were 7.94±0.82, 7.54±0.07 and 8.10±1.87 N, respectively, whereas lateral compression strengths were 8.75±0.82, 14.55±2.29 and 11.12±0.40 N. Compression testing of human samples showed significant differences (P<0.05) between the 3-ring (A-P, 1.06±0.02 N; lateral, 0.55±0.06 N) and 5-ring groups (A-P, 1.08±0.64 N; lateral, 2.32±1.95 N)., Conclusions: The tensile and compressive strengths of mammalian airways show positive correlations with the cartilage ring number (length). On the basis of structural and biomechanical comparisons, porcine, canine and caprine species appear suitable models for the study of airway reconstruction in human., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2970). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Purpose: Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC., Methods: We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity., Results: According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients., Conclusion: Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.

Objectives: To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality., Methods: The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared., Results: The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47-10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P < 0.01), an in-hospital Killip class ≥ 3 (OR = 4.32, 95% CI: 1.71 ~ 10.95, P < 0.01), and the presence of renal insufficiency (OR = 5.32, 95% CI: 1.49 ~ 19.01, P = 0.01), stress ulcer with gastraintestinal bleeding (SUB) (OR = 6.36, 95% CI: (1.45 ~ 28.01, P = 0.01) were significantly related the 10-year mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 (OR = 2.97,95% CI:1.46 ~ 6.03, P < 0.01) and the presence of renal insufficiency (OR = 5.61, 95% CI: 1.19 ~ 26.39, P = 0.03) were significantly related to the 10-year mortality of patients with STEMI and a CTO., Conclusions: The presence of a CTO in a non-IRA, an age ≥ 65 years, an in-hospital Killip class ≥ 3, and the presence of renal insufficiency, and SUB were independent risk predictors for the long-term mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 and renal insufficiency were independent risk predictors for the long-term mortality of patients with STEMI and a CTO.

Background: The overall prognosis of lung cancer remains unfavorable and novel prognostic biomarkers of lung cancer are needed warranted. Accumulating evidence indicate that systemic inflammation plays a vital role in lung cancer. The lymphocyte-to-monocyte ratio (LMR) is biomarker that reflects the level of systemic inflammation., Objective: To perform a comprehensive meta-analysis exploring the correlation of pretreatment LMR with the overall survival (OS) and progression-free survival (PFS) of lung cancer patients., Methods: We conducted searches of the PubMed, Embase, Cochrane Library, and Web of Science databases to May 2020 to identify relevant studies and calculated combined hazard ratios (HRs) to evaluate the association between pretreatment LMR and survival time in patients with lung cancer., Results: A total of 23 studies comprising 8361 lung cancer patients were included. Among the patients, 5702 (68%) were males, 4548 were current smokers and 2212 were diagnosed with squamous carcinoma. The pooled analysis revealed that decreased pretreatment LMR was significantly correlated with reduced of PFS (HR = 1.49, 95% CI: 1.34-1.67, p < 0.01) and reduced OS (HR = 1.61, 95% CI: 1.45-1.79, p < 0.01) among lung cancer patients. Furthermore, in the subgroup analyses according to histologic type, a lower level of pretreatment LMR seemed to be unrelated to the poorer OS of small cell lung cancer (SCLC) patients (HR = 1.21, 95%CI: 0.87-1.67, P = 0.25)., Conclusions: Decreased pretreatment LMR in peripheral blood was associated with shorter OS and PFS in lung cancer patients, suggesting its potential prognostic value.

Background: Asthma is a heterogeneous disease with multiple phenotypes; however, the relevance of phenotype overlap remains largely unexplored., Objective: To examine the relationship between phenotype overlap and clinical and inflammatory profiles of asthma., Methods: In this cross-sectional study, adult participants with stable asthma (n = 522) underwent multidimensional assessments. The 10 most common phenotypes of asthma were defined and then classified into those commonly associated with Type (T) 2 or non-T2 inflammation. Furthermore, phenotype overlap scores (POS), representing the cumulative concomitant phenotypes, were used to analyze its association with clinical and inflammatory asthmatic profiles., Results: Among the 522 participants, 73.4% (n = 383) had phenotype overlap, and mixed T2 and non-T2 inflammation coexisted in 47.5% (n = 248). T2 POS was positively associated with eosinophils, IgE, and fractional exhaled nitric oxide (FeNO), and negatively with Asthma Quality of Life Questionnaire (AQLQ), sputum neutrophils, IL-17A, IL-8, and TNF-α. Non-T2 POS was positively associated with Asthma Control Questionnaire, neutrophils and sputum IL-8, and negatively with AQLQ, forced expiratory volume in 1 s, blood eosinophils, IgE, and FeNO (all P < .05). Patients with phenotypes that are associated with mixed T2 and non-T2 inflammation had elevated T2 inflammation biomarkers but worse asthma control. Both T2 (adjusted β = -0.191, P = .035) and non-T2 (adjusted β = 0.310, P < .001) POS were significantly associated with severe exacerbations., Conclusions: Phenotype overlap is extremely common in asthmatic patients and significantly associated with clinical and inflammatory profiles. Patients with phenotypes associated with mixed T2 and non-T2 inflammation might be unresponsive to medications owing to increased non-T2 inflammation. Multidimensional asthma assessment identifies clinically relevant phenotype overlap., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A crucial issue in cuprates is the extent and mechanism of the coupling of the lattice to the electrons and the superconductivity. Here we report Cu K edge extended X-ray absorption fine structure measurements elucidating the internal quantum tunneling polaron (iqtp) component of the dynamical structure in two heavily overdoped superconducting cuprate compounds, tetragonal YSr 2 Cu 2.75 Mo 0.25 O 7.54 with superconducting critical temperature, T c = 84 K and hole density p = 0.3 to 0.5 per planar Cu, and the tetragonal phase of Sr 2 CuO 3.3 with T c = 95 K and p = 0.6. In YSr 2 Cu 2.75 Mo 0.25 O 7.54 changes in the Cu-apical O two-site distribution reflect a sequential renormalization of the double-well potential of this site beginning at T c , with the energy difference between the two minima increasing by ∼6 meV between T c and 52 K. Sr 2 CuO 3.3 undergoes a radically larger transformation at T c , >1-Å displacements of the apical O atoms. The principal feature of the dynamical structure underlying these transformations is the strongly anharmonic oscillation of the apical O atoms in a double-well potential that results in the observation of two distinct O sites whose Cu-O distances indicate different bonding modes and valence-charge distributions. The coupling of the superconductivity to the iqtp that originates in this nonadiabatic coupling between the electrons and lattice demonstrates an important role for the dynamical structure whereby pairing occurs even in a system where displacements of the atoms that are part of the transition are sufficiently large to alter the Fermi surface. The synchronization and dynamic coherence of the iqtps resulting from the strong interactions within a crystal would be expected to influence this process., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Background: The frequent movement of population between countries brings an increasing number of travel-related infections. This study aims to define the spectrum and dynamics of imported infections observed from international travel in the Chinese mainland., Methods: Sick travellers were screened by inbound sentinel surveillance and post-travel clinic visits from 2014 to 18. The infections were classified as respiratory, gastrointestinal, vector-borne, blood/sexually transmitted and mucocutaneous. The analysed variables included the place of origin of the travellers (Chinese or foreign) and the time when travel-related infection was present (at the time of return, during travel and post-travel visits to the clinic)., Results: In total, 58 677 cases were identified amongst 1 409 265 253 travellers, with an incidence of 41.64/million, comprising during-travel incidence of 27.44/million and a post-travel incidence of 14.20/million. Respiratory infections constituted the highest proportion of illnesses during travel (81.19%, 31 393 of 38 667), which mainly came from Asian countries and tourists; with influenza virus and rhinovirus infections being mainly diagnosed. Vector-borne diseases constituted the highest proportion of post-travel illnesses (98.14%, 19 638 of 20 010), which were mainly diagnosed from African countries and labourers; with malaria and dengue fever being mainly diagnosed. The differential infection spectrum varied in terms of the traveller's demography, travel destination and travel purpose. As such, a higher proportion of foreign travellers had blood/sexually transmitted diseases (89.85%, 2832 of 3152), while Chinese citizens had a higher prevalence of vector-borne diseases (85.98%, 19 247 of 22 387) and gastrointestinal diseases (79.36%, 1115 of 1405). The highest incidence rate was observed amongst travellers arriving from Africa, while the lowest was observed amongst travellers arriving from Europe., Conclusions: The findings might help in preparing recommendations for travellers and also aid in primary care or other clinics that prepare travellers before trips abroad. The findings will also help to identify locations and the associated types of infections that might require attention., (© International Society of Travel Medicine 2020.)

Objective: To evaluate the oncologic and functional outcomes of postcricoid carcinoma treated by surgical treatment, and to summarize our clinical experience in surgical treatment and reconstructive techniques. Methods: Medical files of 45 patients were collected and retrospectively analyzed. The patients received surgical treatments between January 2010 and May 2017 in the Qilu Hospital of Shandong University, including 39 males and 6 females, the age ranged from 41 to 78 years old. T1, T2, T3 and T4 staging tumors represented respectively for 2,13,23 and 7 cases. And cervical metastasis was histologically identified in 33 cases (8 for N1 and 25 for N2). Advanced staging patients (10 in Stage Ⅲ and 30 in Stage Ⅳ) accounted for 88.9% of the cohort, while early staging cases (1 in Stage Ⅰand 4 in Stage Ⅱ) for 10.1%. All patients received cervical lymph node dissection. After tumor excision without compromising margins, hypopharyngeal functions were reconstructed by residual mucosa, pectoralis major myocutaneous flap, laryngotracheal tissue flap or gastric tissue flap, and laryngeal functions were reconstructed by epiglottis, sternohyoid myofascial flap or thyroid perichondrium. Survival rates were analyzed by the Kaplan-Meier method. Results: Postoperatively 23 patients received radiotherapy and 13 patients received chemoradiotherapy. All patients were followed up for more than 3 years. Total 3-year and 5-year survival rates were 60.5% and 49.0%, respectively. Patients obtaining the conservation of laryngeal functions accounted for 44% (20/45) of all cases. The neck lymph node positive rate was 73.3%(33/45), and log-rank test demonstrated that cervical lymph node metastasis was significantly associated with prognosis of patients (χ(2)=4.364, P =0.037). Conclusion: Appropriate surgical approaches and excision methods and comprehensive application of flaps are critical to precise tumor excision and reconstruction of laryngeal functions, thereby improving the quality of life of patients with posterior carcinoma.

Aging is a major risk factor in cardiovascular disease (CVD). Oxidative stress and inflammation are involved in the pathogenesis of CVD, and are closely associated with senescent vascular endothelial cells. Monotropein (Mtp) exerts various bioactive roles, including anti‑inflammatory and antioxidative effects. The aim of the present study was to investigate the function of Mtp in senescent endothelial cells. An MTT assay was performed to evaluate the influence of Mtp on H2O2‑stimulated human umbilical vein endothelial cells (HUVECs). Senescent cells were assessed by determining the expression of senescence‑associated β‑galactosidase, high mobility group AT‑hook 1 and DNA damage marker γ‑H2A.X variant histone. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) and proinflammatory cytokine concentrations were estimated using assay kits to evaluate the levels of oxidative stress and inflammation in HUVECs. The TUNEL assay was performed to identify apoptotic cells. Furthermore, the expression levels of endothelial cell adhesion factors, NF‑κB, activator protein‑1 (AP‑1) and apoptotic proteins were determined via western blotting. Mtp enhanced HUVEC viability following H2O2 stimulation. H2O2‑mediated increases in MDA, proinflammatory cytokine and endothelial cell adhesion factor levels were decreased by Mtp treatment, whereas Mtp reversed H2O2‑mediated downregulation of SOD and GSH‑Px activity. Furthermore, Mtp inhibited cell apoptosis, NF‑κB activation and AP‑1 expression in H2O2‑stimulated HUVECs; however, NF‑κB activator counteracted the anti‑inflammatory, antioxidative and antiapoptotic effects of Mtp. The present study indicated that Mtp ameliorated H2O2‑induced inflammation and oxidative stress potentially by regulating NF‑κB/AP‑1.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage ( p < 0.001) and the presence of lymphovascular invasion ( p = 0.002), whereas patients with UT often had synchronous bladder tumor ( p < 0.001), and were more likely to bear multiple lesions ( p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121-1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169-2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095-1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141-1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT., Competing Interests: The authors declare no conflict of interest.

A photoredox-catalyzed regio- and stereoselective trifluoroethylation reaction of enamides using commercially available 2,2,2-trifluoroethyl iodide as trifluoroethylating agents has been developed, furnishing geometrically defined and synthetically and physiochemically pivotal β-trifluoroethylated enamides bearing a diverse range of functional groups.

Background: Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19., Methods: This is a retrospective multi-centre study involving patients admitted between January 16th and March 10th 2020. The composite endpoint was defined as the presence of at least one of the following, intensive care unit (ICU) admission, or the need for mechanical ventilation, or death., Results: A total of 472 consecutive cases admitted to 51 certified COVID-19 tertiary care hospitals were enrolled (median age was 43 [32-53.5] years and 53.0% were male). There were 101 (21.4%) patients presented with comorbidities, including hypertension (15.0%), diabetes mellitus (7.8%), coronary artery disease (2.6%), chronic obstructive pulmonary disease (1.3%) and cerebrovascular disease (1.9%). The composite endpoint occurred in 65 (13.8%) patients. Multivariate stepwise logistic regression analysis indicated that older age (odds ratio [OR] 1.39, 95% confidence interval (CI) 1.05-1.85, per 10-year increment), antecedent hypertension (OR 2.82, 95% CI 1.09-7.29), neutrophil counts (OR 1.33, 95% CI 1.14-1.56) and lactate dehydrogenase level (OR 1.01, 95% CI 1.00-1.01) were independently associated with the presence of composite endpoint. Hypertensive patients, compared with controls, had a greater chance of experiencing the composite endpoint ( p  < .001) and each individual endpoint, i.e. ICU admission ( p  < .001), mechanical ventilation ( p  < .001) and death ( p  = .012). In the stepwise regression analysis of anti-hypertensive medications, none of the therapy predicted the composite endpoint., Conclusions: Hypertension is a common comorbidity in patients with COVID-19 and associated with adverse outcomes. KEY MESSAGES Hypertension was identified as the comorbidity associated with the prognosis of COVID-19 in this retrospective cohort. Patients with hypertension could experience an increased risk of the composite endpoint. Anti-hypertensive therapy did not affect patient outcomes.

Background: Abnormal extracellular matrix (ECM) remodeling plays an essential role in urothelial carcinoma (UC) invasiveness and metastasis. Focusing on the ECM structural constituent (GO: 0005201), we recognized a significant upregulation of the fibulin 2 gene ( FBLN2 ) during UC progression in a published UC transcriptome (GSE31684). Thus, we aimed to investigate the roles of FBLN2 expression and its prognostic value in upper urinary tract UC (UTUC) and urinary bladder UC (UBUC) in our large, well-characterized cohort. Patients and Methods: Clinicopathological data and formalin-fixed paraffin-embedded UC tissues were analyzed retrospectively. We determined FBLN2 expression using immunohistochemical staining assessed by H-scores. FBLN2 expression correlated with clinicopathological features and patient outcomes, including metastasis-free survival (MFS) and disease-specific survival (DSS). Statistical analyses were performed using Pearson's chi-square test, Kaplan-Meier estimates of DSS and MFS, and the Cox proportional hazards model. We used Ingenuity Pathway Analysis (IPA) to clarify the functional significance of dysregulated FBLN2 in UC. Results: Data from 295 UBUC and 340 UTUC patients were available for the final evaluation. Pearson's chi-square test showed that high FBLN2 immunoexpression significantly correlated with adverse pathologic variables, such as advanced pathologic tumor stage, high histological grade, perineural invasion, vascular invasion, lymph node metastasis, and increased mitotic rate (all p < 0.05). Kaplan-Meier analysis demonstrated associations of high FBLN2 expression with worse DSS ( p < 0.001) and MFS ( p < 0.001). Furthermore, multivariate analysis identified high FBLN2 expression as an independent predictive risk factor for DSS [hazard ratio (HR) in UBUC, 2.306, p = 0.014; in UTUC, 2.561, p = 0.012] and MFS (HR in UBUC, 2.493, p = 0.001; in UTUC, 2.837, p = 0.001). IPA demonstrated that multiple signaling pathways were enriched, including the oxidative phosphorylation, mitochondrial dysfunction, and regulation of the epithelial-mesenchymal transition pathways. Conclusion: High FBLN2 expression was associated with adverse pathologic features and worse oncological outcomes and may serve as a prognostic biomarker for UC., (Copyright © 2020 Li, Chan, Huang, Wu, Ke, Liang, Wei, Shiue and Li.)

Objective: This study aimed to discuss the effects of appetite-conditioned reflex stimulation on the early enteral nutrition (EEN) tolerance, complications, and postoperative hospital stay in patients who underwent surgery., Methods: Seventy patients who underwent laparoscopic radical resection of colorectal cancer surgery in our hospital between February and December 2017 were randomly divided into a stimulated appetite group (experimental group, including visual stimulation, nasal stimulation, taste stimulation and hearing stimulation) and a control group (n = 35). Both groups received EEN. EEN tolerance, complications, and postoperative hospital stay were then compared between the groups., Results: Sixty-six patients, including 34 in the experimental group and 32 in the control group, completed the relevant experiment. The experimental group had significantly lower incidence rates of nausea, vomiting, bloating, use of prokinetic drugs, and gastric tube replacement (P < 0.05), and shorter tolerable regular eating time (5.0 ± 1.0 d vs 6.4 ± 1.9 d, P < 0.05) and postoperative hospital stay (7.0 ± 2.0 d vs 8.0 ± 1.8 d, P < 0.05) than the control group. No significant difference in complication rate was detected (P > 0.05)., Conclusion: Appetite-conditioned reflex stimulation can improve EEN tolerance, decrease the risk of complications, and shorten ordinary diet recovery time and hospital stay., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Urothelial carcinoma (UC), including upper tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC), is a common malignant disease in developed countries. Oncogenic metabolic lesions have been associated with UC development. Methods: Using data mining, a series of studies were performed to study the involvement of SLC14A1 in UC specimens, animal models and UC-derived cell lines. Results: In two cohorts of UTUC ( n = 340) and UBUC ( n = 295), the SLC14A1 protein level was an independent prognostic factor. Epigenetic silencing contributed to SLC14A1 downregulation in UCs. Total and membranous SLC14A1 played tumor suppressive roles through the inhibition of cell proliferation and metastasis in distinct UC-derived cells and animal models. Functional SLC14A1 prevented the accumulation of arginine and urea, enhanced mitochondrial fusion and aerobic respiration, inhibited glycolysis by altering the expression levels of several related proteins and sensitized arginine-deprivation treatment in ASS1 -deficient UC-derived cells. In vitro and in vivo, SLC14A1 inhibited the mTOR signaling pathway and subsequently tumorigenesis, supported by reduced arginine concentrations in vitro. Nuclear SLC14A1 transrepressed HK2 and DEGS1 genes via recruitment of HDAC1 and/or SIN3A to maintain metabolic homeostasis and thereafter impeded tumorigenesis. Conclusion: Clinical associations, animal models and in vitro indications provide solid evidence that the SLC14A1 gene is a novel tumor suppressor in UCs. Total and membranous SLC14A1 prevents urea and arginine accumulation via the mTOR signaling pathway. Nuclear SLC14A1 recruits HDAC1 to transrepress oncometabolite genes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aims: Mesenchymal stem cell (MSC)-derived exosomes (MSCs-exos) regulate biological functions in different diseases, such as liver fibrosis, diabetes, and ischaemic heart injury. However, the function of MSC-derived exosomes on the intestinal barrier and the underlying mechanisms are poorly characterized., Main Methods: The expression of miR-34a/c-5p, miR-29b-3p and Claudin-3 in human normal intestinal tissues and damaged intestinal tissues was evaluated by RT-qPCR. The effect of MSC-secreted exosomes on Claudins in Caco-2 cells was measured by using confocal microscopy, RT-qPCR and Western blot. Dual luciferase reporter assays and RNA immunoprecipitation (RIP) assays were performed to study the interaction between miR-34a/c-5p, miR-29b-3p and Snail. I/R-induced intestinal damage in rats was used to determine the in vivo effect of MSC-exos on intestinal barrier function., Key Findings: In this study, we found that miR-34a/c-5p, miR-29b-3p and Claudin-3 were downregulated in damaged human intestinal tissues. MSC-exos increased the expression of Claudin-3, Claudin-2 and ZO-1 in Caco-2 cells. Further studies demonstrated that MSC-exos promoted Claudin-3, Claudin-2 and ZO-1 expression in Caco-2 cells by Snail, which was targeted by miR-34a/c-5p and miR-29b-3p. In vivo experiments showed that MSC-derived exosomes could improve I/R-induced intestinal damage through the Snail/Claudins signaling pathway., Significance: The findings here suggest a novel molecular basis for the therapy of intestinal barrier dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Although studies have consistently linked obesity and asthma, the potential influence of visceral obesity on asthma has not been well investigated. Objective: To study the associations of visceral fat area (VFA) and clinical and inflammatory features of asthma and to further explore the effects of VFA on the future risk of asthma exacerbation. Methods: A 12-month prospective cohort study based on the Australasian Severe Asthma Network was designed to observe patients with stable asthma grouped by the median value of VFA. The clinical and inflammatory features of asthma were compared between the low VFA (VFA low ) and high VFA (VFA high ) groups. Relationships between VFA and clinical and inflammatory features of asthma were analyzed by using correlation analysis. Univariate and multivariable negative binomial regression analyses were performed to investigate the association of VFA with exacerbations within a 12-month follow-up period. Results: The patients in the VFA high group were older and had a longer asthma duration. Interleukin (IL) 6 and IL-8 in sputum were higher, whereas fractional exhaled nitric oxide (FeNO) and blood eosinophils were lower in the VFA high group. Gender-differentiated correlations of VFA with clinical and inflammatory variables were observed in age, FeNO, immunoglobulin E, blood total white cells and neutrophils, and sputum IL-1β and IL-8. Furthermore, compared with the VFA low group, the VFA high group was at significantly increased risk of moderate-to-severe exacerbations (adjusted incidence rate ratio [IRR] 1.55 [95% confidence interval {CI}, 1.06-2.28; p = 0.025), severe exacerbations (adjusted IRR 2.25 [95% CI, 1.26-4.04]; p = 0.007), and emergency visits (adjusted IRR 5.33 [95% CI, 1.78-17.16]; p = 0.003). Conclusion: The level of VFA was associated with specific clinical and inflammatory characteristics of asthma. Furthermore, VFA, as an independent risk factor, was associated with an increased risk of exacerbations. It indicated that VFA would provide more potential clinical implications for asthma management.

The general secretory (Sec) pathway represents a common mechanism by which bacteria secrete proteins, including virulence factors, into the extracytoplasmic milieu. However, there is little information about this system, as well as its associated secretory proteins, in relation to the fire blight pathogen Erwinia amylovora. In this study, data mining revealed that E. amylovora harbors all of the essential components of the Sec system. Based on this information, we identified putative Sec-dependent secretory proteases in E. amylovora on a genome-wide scale. Using the programs SignalP, LipoP, and Phobius, a total of 15 putative proteases were predicted to contain the N-terminal signal peptides (SPs) that might link them to the Sec-dependent pathway. The activities of the predicted SPs were further validated using an Escherichia coli-based alkaline phosphatase (PhoA) gene fusion system that confirmed their extracytoplasmic property. Transcriptional analyses showed that the expression of 11 of the 15 extracytoplasmic protease genes increased significantly when E. amylovora was used to inoculate immature pears, suggesting their potential roles in plant infection. The results of this study support the suggestion that E. amylovora might employ the Sec system to secrete a suite of proteases to enable successful infection of plants, and shed new light on the interaction of E. amylovora with host plants.

Urothelial carcinoma (UC) is one of the highest incidence cancers that rank the fourth commonly diagnosed tumors worldwide. The unresectable lesions that are resistant to therapeutic interventions is the major cause leading to death. Previous studies had shown that the resistance and metastatic consequence may arise from cancer stem-like cells population. The phytochemical flavonoids have promised bioactivity and potent anti-carcinogenic effects, and trap great attentions for cancer chemoprevention and/or adjuvant chemotherapy. However, the mechanisms of flavonoids on cancer stemness is still obscured. In this study, we analyzed the biofunctional effects of as-prepared flavonoid derivative-WYC0209 on T24, BFTC905 and BFTC909 human UC cell lines. Our results demonstrated that WYC0209 significantly induced anti-cell viability on UC cells through decreased Akt/NFkB signaling. Moreover, WYC0209 enhanced the cell apoptosis through activated the caspase-3 activity and inactivated Bcl-xL expression. Interestingly, WYC0209 dramatically inhibited the cancer stem cells (CSCs) traits, including attenuation of side population and tumorsphere formation in which were through declined EMT-CSCs markers including MDR1, ABCG2 and BMI-1. We further validated the effects of WYC0209 on several CSC surface markers including CD133, CD44, SOX-2 and Nanog. Our results showed that WYC0209 markedly inhibited CD133 expressions in both transcriptional and translational levels. High expression levels of CD133 was also demonstrated in human upper tract UC specimens. In summary, our study showed that WYC0209 may potentially as an adjuvant agent to against CD133-driven UC CSCs and provide a beneficial strategy to against UC cancer therapeutics resistant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This research aimed to develop a direct-write near-field electrospinning system (DW-NFES) with three-axis positioning of controllable speed, torque and position to produce sizable and high-quality piezoelectric fibers for sensing purposes. Sensor devices with high electrical response signals were developed and tested. To achieve DW-NFES purpose, a servo motor controller was designed to develop a high response rate, accurate positioning, and stable mobile device through the calculation of bandwidth and system time delay. With this retooled system of DW-NFES, controllable and uniform size fibers in terms of diameters, stretching force, and interspaces can be obtained. Sensor devices can be made selectively without a complicated lithography process. The characteristics of this DW-NFES platform were featured by high response rate, accurate positioning, and stable movement to make fibers with high piezoelectric property. In this study, polyvinylidene fluoride (PVDF) was used to explore and enhance their sensing quality through the platform. The parametric study of the process factors on piezoelectric sensing signals mainly included the concentration of electrospinning PVDF solution, high voltage electric field, and collection speed. Finally, the surface morphology and piezoelectric properties of the as-electrospun PVDF fibers were examined by scanning electron microscopy (SEM) and characterized by electrical response measurement techniques. The results showed that the fiber spinning speed of the DW-NFES system could be increased to ~125 from ~20 mm/s and the accuracy precision was improved to ~1 from ~50 μm, compared to conventional step motor system. The fiber diameter reached ~10 μm, and the electrospinning pitch reached to as small as ~10 μm. The piezoelectric output voltage of the electrospun fibers was increased ~28.6% from ~97.2 to ~125 mV; the current was increased ~27.6% from ~163 to ~208 nA, suggesting that the piezoelectric signals can be enhanced significantly by using this retooled system. Finally, an external control module (Arduino-MAGE) was introduced to control the PVDF piezoelectric fiber sensors integrated as a sensing array. The behavior of long-term sedentary patients can be successfully detected by this module system to prevent the patients from the bedsores.

Atrial structural and electrical remodelling play important roles in atrial fibrillation (AF). Sacubitril/valsartan attenuates cardiac remodelling in heart failure. However, the effect of sacubitril/valsartan on AF is unclear. The aim of this study was to evaluate the effect of sacubitril/valsartan on atrial electrical and structural remodelling in AF and investigate the underlying mechanism of action. Thirty-three rabbits were randomized into sham, RAP, and sac/val groups. HL-1 cells were subjected to control treatment or rapid pacing with or without LBQ657 and valsartan. Echocardiography, atrial electrophysiology, and histological examination were performed. The concentration of Ca 2+ and expression levels of calcineurin, NFAT, p-NFAT, Cav1.2, collagen Ⅰ and Ⅲ, ANP, BNP, CNP, NT-proBNP, and ST2 in HL-1 cells, and I caL in left atrial cells, were determined. We observed that compared to that in the sham group, the atrium and right ventricle were enlarged, myocardial fibrosis was markedly higher, AF inducibility was significantly elevated, and atrial effective refractory periods were shortened in the RAP group. These effects were significantly reversed by sacubitril/valsartan. Compared to that in the sham group, collagen Ⅰ and Ⅲ, NT-proBNP, ST2, calcineurin, and NFAT were significantly up-regulated, while p-NFAT and Ca v 1.2 were down-regulated in the RAP group, and sacubitril/valsartan inhibited these changes. Ca 2+ concentration increased and I CaL density decreased in in vivo and in vitro AF models, reversed by sacubitril/valsartan. Sacubitril/valsartan attenuates atrial electrical remodelling and ameliorates structure remodelling in AF. This study paves the way for the possibility of clinical use of sacubitril/valsartan in AF patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this work, commercial anatase TiO 2 powders were modified using ultrathin Fe 2 O 3 layer by atomic layer deposition (ALD). The ultrathin Fe 2 O 3 coating having small bandgap of 2.20 eV can increase the visible light absorption of TiO 2 supports, at the meantime, Fe 2 O 3 /TiO 2 heterojunction can effectively improve the lifetime of photogenerated electron-hole pairs. Results of ALD Fe 2 O 3 modified TiO 2 catalyst, therefore, showed great visible light driven catalytic degradation of methyl orange compared to pristine TiO 2 . A 400 cycles of ALD Fe 2 O 3 (~ 2.6 nm) coated TiO 2 powders exhibit the highest degradation efficiency of 97.4% in 90 min, much higher than pristine TiO 2 powders of only 12.5%. Moreover, an ultrathin ALD Al 2 O 3 (~ 2 nm) was able to improve the stability of Fe 2 O 3 -TiO 2 catalyst. These results demonstrate that ALD surface modification with ultrathin coating is an extremely powerful route for the applications in constructing efficient and stable photocatalysts.

Objective: We sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with COVID-19 in a region of China where medical resources are less stressed than in Wuhan (the epicentre of the pandemic)., Methods: We prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit., Results: A total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34-62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p<0.001) and treatment with vasoactive agents (31.2% vs 0%, p<0.001). Log hs-TnT was associated with disease severity (OR 6.63, 95% CI 2.24 to 19.65), and all of the three deaths occurred in patients with acute myocardial injury., Conclusion: Acute myocardial injury is common in patients with COVID-19 and is associated with adverse prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare the safety profile, angiographic and clinical outcomes between drug-coated balloon(DCB) only strategy versus drug eluting stent(DES) implantation in primary percutaneous coronary intervention(PCI) for acute myocardial infarction(AMI) patients. Methods: A total of 380 AMI patients who underwent primary PCI in Beijing Chaoyang Hospital from January 2016 to May 2019 were enrolled. They were allocated into DEB group( n= 180) or DES group( n= 200). The Primary endpoint was the major adverse cardiac events(MACE) in hospital and within 3 months after discharge, the composite event of cardiac death, non-fatal myocardial infarction(MI), target vessel revascularization(TVR) and in stent thrombosis. The secondary endpoints included: (1)TIMI blood flow grade and myocardial perfusion grade (TMP grade) of infarct-related vessels before and after PCI. (2)The degree of ST segment resolution(STR) between half hour and two hours after PCI, and STR was represented by percentage of summed ST-segment reduction between baseline and post-PCI. Using the most significant lead of ST segment elevation, calculating the rate of decline in the ST segment after treatment; or the most significant lead of the ST segment depression, to calculate the rate of recovery in the ST segment after treatment. STR<50% was defined as incomplete STR. (3)The occurrence of coronary artery dissection during operation. (4)The peak value of myocardial enzymes. (5)The incidence of bleeding in hospital and within 3 months after discharge. The inverse probability weighting method based on propensity score (IPTW) was used to compare the effects of the two treatments on MACE occurrence in the logistic regression model. Results: There was no significant difference in sex, age, risk factors of coronary heart disease, type and site of AMI, interventional therapy data( P> 0.05) between the two groups. The ratio of bifurcation lesions in DCB group was significantly higher than that in DES group, and the diameter of the DCB was smaller while the length was longer than that of DES (all P< 0.05). One death occurred in each group during hospitalization. Compared with the DES group, the incidence of MI ［2.8%(5/180) vs. 0.5% (1/200), P= 0.10］ and TVR ［2.8%(5/180) vs. 0.5%(1/200), P= 0.10］ in the DCB group during hospitalization showed an increasing trend, and were mostly associated with delayed coronary dissection. The incidence of MACE was similar between the two groups (3.3%(6/180) and 1.0%(2/200), P= 0.15) during hospitalization. There was no MACE occurred in the two groups within 3 months after discharge. There was no significant difference between the two groups in TIMI grade, TMP grade, incomplete STR rate and peak value of myocardial enzyme (all P> 0.05). The incidence of coronary artery dissection was significantly higher in DCB group than in DES group (8.3%(15/180) and 3.0%(6/200), P= 0.02), but most of them were type B or A dissection and did not need special treatment. There was no significant difference in bleeding event between the two groups( P= 0.91). Logistic regression analysis showed that there was no difference in the risk of MACE during hospitalization between DES and DCB groups for AMI patients receiving PCI (compared with DCB, OR= 0.35, 95 %CI 0.08-1.43, P= 0.13). Conclusions: The initial safety and efficacy profiles of DCB are similar with those of DES for the AMI patients during PCI. The study highlights that the incidence of coronary dissection (type A or B) is higher post DCB treatment than post DES, but it does not affect blood flow. However, the incidence of in-hospital MI due to delayed coronary dissection trends to be higher post DCB. So we should pay close attention to the risk of delayed coronary dissection after DCB in AMI patients with de novo lesion.

Hierarchical iron-nitrogen-codoped porous hollow carbon spheres have been synthesized by using melamine-formaldehyde (MF) resin spheres as templates, nitrogen sources and pore-forming agents. FeCl3, 1,10-phenanthroline and carbon black were used as iron, nitrogen and carbon sources. The as-obtained porous hollow carbon spheres possess a high specific surface area of 807 m2 g-1, as well as exhibited excellent electrocatalytic activity for the oxygen reduction reaction (ORR) in both acidic and alkaline media. In 0.1 M HClO4 solution, the onset potential was 0.857 V (vs. RHE) and the half-wave potential was 0.715 V, which are only 78 and 80 mV less than those of the 20% Pt/C catalyst, respectively. In addition, in 0.1 M KOH solution, the onset potential was 1.017 V and the half-wave potential was 0.871 V for the ORR, which are 22 and 28 mV more positive than those of the Pt/C catalyst, respectively. Meanwhile, the catalyst also exhibited excellent methanol tolerance and long-term durability with a more effective four-electron pathway compared to the 20% Pt/C catalyst in both acidic and alkaline media. When used as an air-cathode catalyst for a Zn-air battery, the maximum power density of a Zn-air battery with the MF-C-Fe-Phen-800 cathode was 235 mW cm-2 at a high current density of 371 mA cm-2, and a high open-circuit potential of 1.654 V, superior to that of Pt/C (199 mW cm-2, 300 mA cm-2, 1.457 V). A series of designed experiments suggested that the remarkable performance was attributed to the high specific area, hollow carbon spheres, unique hierarchical micro-mesoporous structures, high contents of pyridinic-N and graphitic-N. The superiority of the as-prepared catalyst makes it promising for use in practical applications.

Objective: To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase. Methods: From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy. Results: The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P <0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P <0.001) and longer duration of imatinib therapy ( P <0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions: Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

Tropical race 4 of Fusarium oxysporum f. sp. cubense (FocTR4) is seriously threatening the banana industry worldwide. Resistant genotypes are present in wild relatives of banana, but little is known about the genetic and molecular mechanisms driving resistance responses. In this work, through in-depth expression analysis, we compared the responses of the resistant wild relative Musa acuminata ssp. burmanicoides (WTB) with the susceptible banana cultivar "Brizilian" (CAV, as it belongs to the Cavendish subgroup) to FocTR4 infection. Our findings showed that 1196 defense-related genes in the resistant WTB were differentially expressed genes (DEGs); only 358 defense-related DEGs were detected in CAV. DEGs related to pattern recognition receptors (PRRs) and disease resistance (R genes) were found in both genotypes, indicating the onset of both basal and specific defenses to FocTR4. Genes associated with cell wall modification exhibited a more remarkable upregulation in WTB than in CAV and might be involved in resistance during penetration steps. Our data also suggested that the high resistance of WTB is quantitatively driven with larger numbers and higher expression levels of defense-related DEGs. Fine-tuning studies to understand the resistance responses of WTB at early stages should be conducted to better support banana breeding programs. Further investigations are also required to validate the role of key genes screened in this study.