Search

Coagulation has been accepted as a cost-effective and environmental-friendly method to remove pollutants. In our recent work, two coagulants of polyaluminum chloride (PAC) and polyaluminum ferric chloride (PAFC) with dosage gradients, and one coagulant aid of anionic polyacrylamide (PAM) were used to investigate their potential to remove particle-associated (PA) and free-living (FL) ARGs and MGEs detected by high throughput qPCR (HT-qPCR) method. The results indicated that the maximum removal efficiencies of PA- and FL-ARGs (4.67- and 3.18-logs) were obtained at the PAFC dosage of 50.0 mg/L. Excessive PAFC dosage can hamper the removal of size-fractionated ARGs. As PAC aid, anionic PAM (1.0 mg/L) had limited effects to promote the removal of PA-ARG, while FL-ARG removal was enhanced by 0.34 log at the PAC dosage of 50.0 mg/L. The fitted curves suggested that the optimal chemical dosages of PAC, PAFC and PAC coupled with PAM in the removal of total ARGs and MGEs were 40.5, 64.7 and 50.0 mg/L, respectively. In addition, we found that much more coagulants were needed to remove FL-ARGs compared to that of PA-ARGs. The removal efficiencies of size-fractionated ARGs by flocculation can be affected by coagulant type, dosage, coagulant aid, Zeta potential and microorganism lifestyle (PA or FL)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Fascia iliaca compartment block (FICB) is an anterior approach to the lumbar plexus block and provides the effective adjunctive analgesia for total hip arthroplasty (THA)., Methods: As a case series study, 28 patients (≥ 65 years old) with THA were received a modified in-plane ultrasound-guided supra-inguinal (S-FICB) as an analgesic adjunct to evaluate the analgesic effectiveness and the local anesthetic diffusion with magnetic resonance imaging (MRI). A combination of propofol and sufentanil was administered to conduct target-controlled infusion., Results: The pain scores were 1 (0-4), 2 (1-5), 3 (1-6) and 3 (1-6) at 4, 8, 12, and 24 h. The cumulative opioids were 8 (8-12), 18 (16-32), 28 (24-54) and 66 (48-104) mg of i.v. morphine equivalents at 4, 8, 12, and 24 h. The patient-controlled analgesia (PCA) times were 0 (0-1), 1 (0-2), 2 (0-5) and 5 (3-8) at 4, 8, 12, and 24 h. In lateral, anterior and medial part of thigh, the sensory blockade in 28 patients was 23 (82 %), 21 (75 %) and 19 (68 %) at 5 min; 28 (100 %) at 10 and 20 min. Motor blockade of femoral nerve (FN) and obturator nerve (ON) was present in 13 (46 %) and 3 (11 %) patients at 5 min, 24 (86 %) and 9 (32 %) at 10 min, 26 (93 %) and 11 (39 %) at 20 min. Injectate permeated to the FN and extended superiorly over the surface of iliac muscle (IM) and pectineus muscle (PM) in all patients., Conclusions: The modified S-FICB has provided an effective postoperative analgesic adjunct after THA with the satisfactory blockade of femoral (FN), obturator (ON) and sciatic (SN) nerves, especially for ON, when compared with the existing techniques.

Purpose: To explore the regulatory relationship between Chloride intracellular channel 1 (CLIC1) and Angiomotin (AMOT)-p130, and reveal the role of AMOT-p130 in gastric cancer (GC)., Methods: Immunohistochemistry was performed to analyze the expression of CLIC1 and AMOT-p130 in GC tissues and adjacent tissues. The expression of AMOT-p130 upon CLIC1 silencing was analyzed using RT-PCR, western blot, and immunofluorescence in GC cells. Transwell and wound-healing assays were performed to detect migration and invasion in GC cells. The changes in EMT-related proteins were detected using western blot., Results: Our study found that high CLIC1 expression was significantly associated with low AMOT-p130 expression in GC tissues. Silencing CLIC1 expression in MGC-803 cells (MGC-803 CLIC1 KO) and AGS cells (AGS CLIC1 KO) decreased the invasive and migratory abilities of tumor cells, which were induced by the upregulation of AMOT-p130. Subsequently, we demonstrated that AMOT-p130 inhibits the invasive and migratory abilities of GC cells by inhibiting epithelial-mesenchymal transition., Conclusions: Our study suggests that AMOT-p130 could inhibit epithelial-mesenchymal transition in GC cells. CLIC1 may participate in the metastatic progression of GC by downregulating the expression of AMOT-p130.

Background: Few studies from developed countries have quantitatively characterized the clinical characteristics and outcomes of patients receiving contemporary intensive cardiac care. We sought to investigate these data in patients admitted to a Chinese intensive cardiac care unit (ICCU)., Methods: We conducted a retrospective study using data from 2,337 consecutive admissions to the ICCU at a large centre in China from June 2016 to May 2017. Data were captured after systematic inspection of individual medical records regarding current demographics, primary diagnosis, comorbidities, illnesses severity, and in-hospital outcomes., Results: The mean age was 65.6 ± 14.2 years, and females accounted for 32.0% of patients. The Charlson Comorbidity Index and Oxford Acute Severity of Illness Score were 2.4 ± 1.8 and 22.5 ± 10.4, respectively. The top reason for admission was ST-segment elevation myocardial infarction (32.0%), and nonischaemic heart diseases accounted for 31.2% of all primary diagnoses. Noncardiovascular diseases were prevalent in the ICCU population, including chronic illnesses and acute noncardiovascular critical illnesses (ANCIs); in particular, 21.7% of patients were marked by acute respiratory failure (14.6%), acute kidney injury (13.7%), sepsis (4.2%), or gastrointestinal bleeding (3.3%). The median length of stay in the ICCU and hospital were 1.1 days [interquartile range (IQR): 0.8-2.6 days] and 6.3 days (IQR: 3.8-10.9 days), respectively. The overall incidence of in-hospital death or discharge against medical advice under extremely critical conditions was 7.6% ( n = 177). Multivariate logistic regression analysis showed that the complexity of chronic illnesses and incident ANCIs were strong independent determinants for in-hospital outcomes., Conclusions: Remarkable patient diversity and breadth of critical illnesses were observed in a Chinese ICCU population. Particularly, noncardiovascular diseases were prevalent and associated with adverse outcomes. Reformation of organization and staffing practices may be considered to adapt to the changed landscape., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Studies about medical care needs for home healthcare (HHC) previously focused on disease patterns but not gender and income differences. We used the Taiwan National Health Research Insurance Database from 1997 to 2013 to examine trends in medical care needs for patients who received HHC, and the gender and income gaps in medical care needs, which were represented by resource utilization groups (RUG). We aimed to clarify three questions: 1. Are women at a higher level of medical care needs for HHC than men, 2. Does income relate to medical care needs? 3. Is the interaction term (gender and income) related to the likelihood of medical care needs? Results showed that the highest level of medical care need in HHC was reducing whereas the basic levels of medical care need for HHC are climbing over time in Taiwan during 1998 and 2013. The percentages of women with income-dependent status in RUG1 to RUG4 are 26.43%, 26.24%, 30.68%, and 32.07%, respectively. Women were more likely to have higher medical care needs than men (RUG 3: odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10-1.25; RUG4: OR = 1.13, 95% CI = 1.06-1.22) in multivariates regression test. Compared to the patients with the high-income status, patients with the income-dependent status were more likely to receive RUG3 (OR = 2.34, 95% CI = 1.77-3.09) and RUG4 (OR = 1.98, 95% CI = 1.44-2.71). The results are consistent with the perspectives of fundamental causes of disease and feminization of poverty theory, implying gender and income inequalities in medical care needs. Policymakers should increase public spending for delivering home-based integrated care resources, especially for women with lower income, to reduce the double burden of female poverty at the higher levels of medical care needs for HHC., Competing Interests: The authors have declared that no competing interests exist.

Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)-induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX-induced reduction of Akkermansia muciniphila ( Akk ). Direct replenishment of Akk is sufficient to correct the OVX-induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM- and Akk -induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX-induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM-induced anti-osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Antibiotic resistance genes (ARGs) are considered emerging contaminants posing an increasing threat to the ecological environment and global human health. Profiling ARGs in tailings ponds is essential to better understand their spatial and temporal dynamics. In this study, high-throughput quantitative polymerase chain reaction (PCR) techniques were used to investigate the occurrence, diversity, abundance, and distribution of ARGs in a tailings pond. A total of 97, 52, 44, and 56 ARGs were detected in WK0, WK1, WK2, and HS, respectively, with 11, 6, 3, and 6 mobile genetic elements (MGEs) also being detected, respectively. The absolute abundance of ARGs in the pond water ranged from 6.39×10 7 to 1.75×10 8 copies·L -1 . Additionally, the abundance of MGEs were higher than ARGs in WK1 and WK2, indicating the potential for horizontal gene transfer (HGT). Furthermore, Cu, TOC, and MGEs were significantly associated with ARGs. Indeed, redundancy analysis (RDA) revealed that Cu, TOC, and MGEs explained 61.64% of the alteration of the ARG profiles, implying their potential roles in the spread and evolution of ARGs in tailings ponds.

Toxicarioside O (TCO), a natural product derived from Antiaris toxicaria , has been identified to be a promising anticancer agent. In this study, we aimed to investigate the effect of TCO on the proliferation and epithelial-mesenchymal transition (EMT) of lung cancer cells and its molecular mechanisms. Here, we indicated that TCO inhibits the proliferation of lung cancer cells both in vitro and in vivo . Our results demonstrated that TCO induces apoptosis in lung cancer cells. Moreover, we found that TCO suppresses EMT program and inhibits cell migration in vitro . Mechanistically, TCO decreases the expression of trophoblast cell surface antigen 2 (Trop2), resulting in inhibition of the PI3K/Akt pathway and EMT program. Overexpression of Trop2 rescues TCO-induced inhibition of cell proliferation and EMT. Our findings demonstrate that TCO markedly inhibits cell proliferation and EMT in lung cancer cells and provides guidance for its drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Huang, Dai, Wang, Lin, Sun, Tan and Huang.)

Bereavement, the experience of losing a loved one, is one of the most catastrophic but inevitable events in life. It causes grief and intense depression-like sadness. Recent studies have revealed the effectiveness and proficiency of mindfulness-based cognitive therapy (MBCT) in emotional regulation among bereavement populations. MBCT improves the well-being of the bereaved by enhancing cognitive performances. Regarding the neural correlates of bereavement grief, previous studies focused on the alleviation of emotion-cognition interferences at specific brain regions. Here, we hypothesized that the bereavement grief fundamentally triggers global alterations in the resting-state brain networks and part of the internetwork connectivity could be reformed after MBCT intervention. We recruited 19 bereaved individuals who participated the 8-week MBCT program. We evaluated (a) the large-scale changes in brain connectivity affected by the MBCT program; as well as (b) the association between connectivity changes and self-rated questionnaire. First, after MBCT, the bereaved individuals showed the reduction of the internetwork connectivity in the salience, default-mode and fronto-parietal networks in the resting state but not under emotional arousal, implying the alleviated attention to spontaneous mind wandering after MBCT. Second, the alterations of functional connectivity between subcortical (e.g., caudate) and cortical networks (e.g., cingulo-opercular/sensorimotor) were associated with the changes of the mindfulness scale, the anxiety and the emotion regulation ability. In summary, MBCT could enhance spontaneous emotion regulation among the bereaved individuals through the internetwork reorganizations in the resting state., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Perfluoroalkyl substances (PFASs) are found globally in the environment, but for Taiwan there is a lack of studies on PFAS occurrence, source apportionment, and health risks in drinking water sources. We collected surface water samples from the Baoshan Reservoir of Taiwan and used Positive Matrix Factorization to attribute PFAS contaminants to possible sources. The health index (HI) was used to evaluate the health risk, which was then compared to various international advisory level guidelines. PFOA and PFOS were found to be the most predominant compounds, with concentrations averaging 20.2 ng/L and 16.7 ng/L, respectively. The joint contribution of domestic and commercial waste totaled 61.2% as the predominant source of pollution, followed by urban activities as a secondary source contributing 38.8%. Using the USEPA reference dose, a health risk analysis of Baoshan Reservoir drinking water did not reflect a formal high health risk (HI < 1.0), however potential risks to human health may be present since the sum of PFOA and PFOS (130 ng/L) exceeded the USEPA Lifetime Health Advisory level (70 ng/L). This investigation provides information and reference points for further reviews of PFAS presence in public water supplies., 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 Ltd. All rights reserved.)

Background: The relationship between renal function and outcomes among patients with hypertrophic cardiomyopathy (HCM) remains undefined. We sought to investigate the prevalence of renal dysfunction and its prognostic value in HCM patients., Methods: A total of 581 patients with HCM were consecutively recruited. The chronic kidney disease epidemiology equation was used to estimate the glomerular filtration rate (eGFR). Patients were divided into 2 eGFR categories: ≥60 or <60 ml/min/1.73 m 2 . The predictive value of renal function was assessed using Cox regression., Results: The proportions of eGFR 60-90 ml/min/1.73 m 2 and <60 ml/min/1.73 m 2 were 41.8% and 15.3%, respectively. Estimated GFR independently predicted the risk of all-cause mortality [HR 0.98, 95% confidence interval (CI) 0.96-0.99, P < 0.001]. Compared to those with eGFR ≥ 60 ml/min/1.73 m 2 , patients with eGFR < 60 ml/min/1.73 m 2 were independently associated with all-cause mortality (HR, 3.42 95% CI 1.86-6.28), cardiovascular mortality (HR 2.98, 95% CI 1.36-6.50) and combined adverse outcomes (HR 1.60, 95% CI 1.02-2.49). HRs for all-cause mortality with renal dysfunction were attenuated in patients with older ages (P for interaction = 0.034)., Conclusions: Renal dysfunction is a common comorbidity in HCM. Renal function is an independent predictor of outcomes in patients with HCM. These findings highlight the clinical importance of renal dysfunction in HCM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Serratia marcescens strain ZZCCN01 was isolated from the cardiac blood of a dead beef cow with a lung infection and a foam-like secretion from the nostril. Here, we introduce the 5.1-Mb draft genome sequence, which comprises 105 scaffolds, and the corresponding annotation., (Copyright © 2020 Zhang et al.)

Background: Neonatal listeriosis is a major cause of mortality in newborn; however, there is limited information about this disease in Taiwan. The aim of our study was to identify the outcome determinants, clinical features, and incidence of pregnancy-associated listeriosis, which includes both neonatal and maternal listeriosis., Methods: We retrospectively analyzed the medical records of neonatal and maternal patients with pregnancy-associated listeriosis at two hospitals in Taiwan from January 2000 to December 2018. Listeriosis was indicated by positive Listeria monocytogenes culture., Results: Our study examined 18 neonates and 19 mothers. The neonatal and fetal death rate was 24%. All five cases of fetal losses or neonatal deaths occurred before 29 weeks of gestational age. The annual incidence of confirmed neonatal listeriosis increased significantly from 0.94/10,000 neonatal inpatients in 2000-2011 to 5.45/10,000 neonatal inpatients in 2012-2018 (p = 0.026). Clinical presentations of neonatal listeriosis included respiratory distress (85%), leukocytosis or leukopenia (77%), bandemia (69%), thrombocytopenia (77%), hypocalcemia (100%) and elevated C-reactive protein (CRP) levels (92%). Lower gestation correlated with a higher fatality rate (p = 0.002). Among the maternal cases investigated, 67% had a diagnosis of listeriosis, and 72% presented with fever. However, only 21% of the 19 mothers received complete antepartum ampicillin treatment., Conclusions: The incidence of neonatal listeriosis is increasing, especially in preterm neonates. Maternal listeriosis should be adequately treated with appropriate empirical antibiotics., (Copyright © 2019. Published by Elsevier B.V.)

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: Gender plays a crucial role in the prevalence, clinical presentation, management and outcomes of various cardiovascular diseases. The aim of this study was to evaluate the impact of gender on clinical manifestations and outcomes in the Chinese patients with hypertrophic cardiomyopathy (HCM)., Methods: We evaluated 576 Chinese patients (316 males) who were diagnosed with HCM at West China Hospital from 2008 to 2016 and followed over 3.2 ± 2.3 years., Results: Compared to male patients, female patients were older (57.2 ± 16.7 years vs. 53.0 ± 15.7 years, P = 0.002) and more symptomatic [New York Heart Association class III-IV symptoms 46.9% vs. 30.7%, P < 0.001] at the time of diagnosis, and had higher left ventricular outflow tract gradient at rest [33 (12-58) mmHg vs. 24 (8-42) mmHg, P = 0.007]. During the follow-up period, survival analysis showed no significant differences in the incidences of all-cause mortality (P = 0.657) and cardiovascular mortality (P = 0.214) but the rate of rehospitalization due to heart failure was higher in females than in males (P = 0.015). Multivariable Cox analysis showed that left ventricular ejection fraction (hazard ratio [HR], 0.96 [95% confidence interval [CI], 0.94-0.99]; P = 0.003) and New York Heart Association class III-IV (HR, 2.86 [95% CI, 1.38-5.94]; P = 0.005) were independently associated with cardiovascular mortality., Conclusions: Compared to males, females were older and more symptomatic at presentation, and had higher risk of progression to heart failure in Chinese HCM patients but there were no differences in cardiovascular mortality., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objective: To observe the effect of Fu 's subcutaneous needling on thickness and elasticity of affected muscles in subjects with shoulder neck pain by ultrasonic elastography., Methods: A total of 30 subjects with upper trapezius pain and local tenderness, or stiffness and funicular nodules were observed randomly, right shoulders were as observation group and left shoulders were as control group. Simple resistance training was adopted in the control group. At the same time of the resistance training, sweeping technique of Fu 's subcutaneous needling was adopted at the local tenderness or the stiffness and funicular nodules of upper trapezius in the observation group. The treatment was given once in both groups. Before and immediately after treatment, thickness and elasticity of bilateral upper trapezius and supraspinatus were observed by ultrasonic elastography, and the variations of visual analogue scale (VAS) score were observed in the two groups., Results: Compared before treatment, the elasticity of upper trapezius and supraspinatus were decreased after treatment in both groups ( P <0.05), and those in the observation group were lower than the control group ( P <0.05). Compared before treatment, the VAS scores after treatment were decreased in both groups ( P <0.05), and that in the observation group was lower than the control group ( P <0.05)., Conclusion: Fu 's subcutaneous needling can increase the elasticity and release the muscular tension of affected muscles, and relieve pain in subjects with shoulder neck pain.

Microplastics (MPs) and antibiotic resistance genes (ARGs) are both considered emerging contaminants of increasing concern because their combined pollution poses a serious risk to the ecological environment and human health. In this study, high-throughput quantitative PCR techniques were used to investigate the diversity and abundance of ARGs in river water, to which two different microplastics (PVC and PVA) were added for aerated incubation. The results showed that ARGs in river water were diverse, and microplastics could induce more types of ARGs. Although the number and abundance of ARGs decreased in all three treatments, which were cultivated for 14 d by aeration, compared to those in non-treated samples, the total abundance of ARGs in treatments aerated with MPs were higher than those aerated without MPs, especially in the samples treated with water-soluble microplastics (PVA). Significant correlations between the abundance of ARGs and mobile genetic elements (MGEs) were observed, implying that the occurrence of MGEs may potentially affect the transmission and distribution of ARGs through horizontal gene transfer (HGT) in river water.

Background: The oncolytic Newcastle disease virus (NDV) is inherently able to trigger the lysis of tumor cells and induce the immunogenic cell death (ICD) of tumor cells and is also an excellent gene-engineering vector. The macrophage inflammatory protein-3α (MIP-3α) is a specific chemokine for dendritic cells (DCs). Thus, we constructed a recombinant NDV expressing MIP-3α (NDV-MIP3α) as an in vivo DC vaccine for amplifying antitumor immunities., Methods: The recombinant NDV-MIP3α was constructed by the insertion of MIP-3α cDNA between the P and M genes. Western blotting assay and ELISA were used to detect MIP-3α, HMGB1, IgG, and ATP in the supernatant and sera. The chemotaxis of DCs was examined by Transwell chambers. The phenotypes of the immune cells (eg, DCs) were analyzed by flow cytometry. The antitumor efficiency of NDV-MIP3α was observed in B16 and CT26 tumor-bearing mice. Immunofluorescence and immunohistochemistry were applied to observe the ecto-calreticulin (CRT) and intratumoral attraction of DCs. Adoptive transfer of splenocytes and antibodies and depletion of T-cell subsets were used to evaluate the relationship between antitumor immunities and the role of the T-cell subtype., Results: The findings show that NDV-MIP3α has almost the same capabilities of tumor lysis and induction of ICD as the wild-type NDV (NDV-WT). MIP-3α secreted by NDV-MIP3α could successfully attract DCs in vitro and in vivo. Both B16 and CT26 cells infected with NDV-MIP3α could strongly promote DC maturation and activation. Compared with NDV-WT, intratumoral injection of NDV-MIP3α and the adoptive transfer of T lymphocytes from mice injected with NDV-MIP3α resulted in a significant suppression of B16 and CT26 tumor growth. The NDV-MIP3α-induced production of tumor-specific cellular and humoral immune responses was dependent on CD8 + T cells and partially on CD4 + T cells. A significant reversion of tumor microenvironments was found in the mice injected with NDV-MIP3α., Conclusions: Compared with NDV-WT, the recombinant NDV-MIP3α as an in vivo DC vaccine demonstrates enhanced antitumor activities through the induction of stronger system immunities and modulation of the tumor microenvironment. This strategy may be a potential approach for the generation of an in vivo DC vaccine., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

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.)

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10 -5 ; C allele, OR = 1.32, P = 8.1 × 10 -4 ). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.

Objective: To investigate the effect and mechanism of miR-124-3p-targeing regulating ABCA2 on chronic myelogenous leukemia cell K562-R., Methods: CML cells with miR-124-3p-overexpression and ABCA2-over-expression as well as subcutaneoustrans planted tumor nude mice were used as study objects. And the CML cells were divided into four groups: K562-R blank control, miR-124-3p mimic control, ABCA2-overexpression and mimic+PC ABCA2. The effects of miR-124-3p and ABCA2 on CML cells were analyzed. The levels of proliferation-, apoptosis- and autophagy- related protein were determined by Western blot. qRT-PCR was employed to detect the levels of miR-124-3p and ABCA2 in K562-R cells. The relationship between miR-124-3p and ABCA2 was validated by luciferase reporter system assays and bioinformatics. Hoechst/immunohistochemical staining and CCK-8 assay were performed to investigate the function involved., Results: miR-124-3p highly expressed in K562-S cells and lowly expressed in K562-R cells, however, ABCA2 lowly expressed in K562-S cells and highly expressed in K562-R cells. Over-expression of miR-124-3p significantly decreased ABCA2 level and cell growth, but increased autophagy and apoptosis in K562-R cells (P＜0.01). When ABCA2 was over-expressed, the K562-R cell growth was promoted and autophagy and apoptosis were inhibited (P＜0.01). The miR-124-3p promoted cell autophagy and apoptosis but inhibited cell growth in nude mice transplant tumor model (P＜0.01)., Conclusion: miR-124-3p can target ABCA2 to inhibit the growth of CML cells and promote the cell autophagy and apoptosis of CML cells.

Antibiotic resistome is a raising concern around the world, especially considering treated wastewater for reclamation. A wastewater reclamation system (WWRS), composed by a treatment system (TS) and a reclaimed system (RS) with supplementation from the treated effluent and considered as an integrated system of treatment and reclamation, was selected in this study. High-throughput qPCR (HT-qPCR) was applied to profile 283 antibiotic resistance genes (ARGs) and 12 mobile genetic elements (MGEs) in the WWRS. A total of 251 ARG and 12 MGE subtypes were detected in the WWRS. The TS exhibited good performance for the removal of ARGs with the number, relative and absolute abundances of ARGs largely decreased (99.07% removal efficiency) in the final effluent, which might be ascribed to biosolid sedimentation. Enhancement of biosolids removal contributed the lessening of ARGs. In the RS, high quality effluent significantly reduced the number and abundance of ARGs along the flow to downstream. MGEs were less reduced in the treated effluent than that of the influent (R 2  = -0.16, p > 0.05), and exhibited close connections with ARGs. Arcobacter, Cloacibacterium, Cyanobacteria, Acinetobacter, Flavobacterium and Dechloromonas were the relatively abundant genera in the WWRS, and exhibited significantly correlations with ARGs. Microbial communities and MGEs contributed 65.64% to the changes of ARGs. These two factors may be the main drivers of ARG proliferation in the WWRS. Thus, attention should be paid to MGEs and those abundant genera when considering treated wastewater for reclamation., 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 Ltd. All rights reserved.)

Background: Children with tracheostomy are at increased risk for respiratory tract infections, yet the risk involved in tracheostomy related infections is unclear., Methods: We conducted a retrospective review of the medical records of children who underwent tracheostomy between January 2002 and December 2016 at a teaching hospital in Taipei. Demographics, underlying disease, indication for tracheostomy, laboratory data and management, and long-term outcome data were collected. Infection episodes were grouped into definite, possible, non-bacterial pneumonia, and local infection groups., Results: Ninety patients were enrolled. Forty-two (46.7%) patients had infections that required hospitalization. Definite bacterial pneumonia accounted for 12 (8.5%) episodes, 113 episodes (80.1%) were possible bacterial pneumonia, 12 (8.5%) were non-bacterial pneumonia, and 4 (2.8%) were local infections. Patients with definite and possible bacterial pneumonia were found to have a longer hospital duration than patients with non-bacterial pneumonia (p=0.024), with mean hospitalization stays of 8.83±5.59 days and 5.67±2.55 days, respectively. The median duration from tracheostomy to bacterial pneumonia was 1.78 years (range, 0.04- 11.38) whereas for the non-bacterial pneumonia group it was 0.57 years (range, 0.04-6.61). Cerebral palsy (CP) (adjusted odds ratio [AOR] 3.65; 95% confidence interval [CI]: 1.11-11.99; p=0.033) and gastroesophageal reflux disease (GERD) (AOR 2.84; 95% CI: 1.09-7.38; p=0.033) were independently associated with respiratory tract infections in these children., Conclusion: In this study, CP and GERD were associated with infections in children with tracheostomy. Bacterial and non-bacterial pneumonia are difficult to differentiate clinically which may lead to unnecessary antibiotics use., (Copyright © 2018. Published by Elsevier B.V.)

Landfills leachate contained diverse antibiotic resistance genes (ARGs). Treated landfill leachate effluent could enter into the downstream environments, leading to the dissemination of ARGs, which might pose a health risk to public. Here, we used high-throughput qPCR to characterize the resistome and 16S rRNA-based Illumina sequencing to analyze the bacterial community in a leachate treatment plant and the river near the landfill. A total of 91 ARGs and 5 mobile genetic elements were detected. Leachate treatment process significantly changed the profiles of resistome and bacterial community structures. Similar bacterial community structure and ARG profiles were detected between effluent and downstream river, which were both dominated by multidrug and beta-lactams resistance genes and harbored higher ARG relative abundance than that in upstream river. In particular, seven ARGs were detected both in effluent and downstream river samples but not detected in upstream river, including genes encoding resistance to vancomycin (vanXD and vanSB) and carbapenem (cphA and blaGES), which implied the effects of the effluent on its receiving river. This study highlights the risk of discharge of processed landfill leachate in dissemination of antibiotic resistance determinants to the environments, and suggests an urgent need for surveillance of ARGs and development of techniques to mitigate the risk., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To observe the difference of pulmonary function among patients with dysphagia after stroke, patients without dysphagia and normal people, and to explore the correlation between swallowing function and pulmonary function. Methods: From September 2018 to April 2019, 310 stroke patients were enrolled from the rehabilitation department and neurology department of sun yat-sen memorial hospital, sun yat-sen university, of which 60 were selected as standard stroke patients. Pulmonary function of the three groups was assessed by pulmonary function detector and further compared. The swallowing function of the dysphagia group after stroke was examined by using videofluroscopic swallowing study (VFSS). The swallowing function was quantitatively assessed by Rosenbek penetration-aspiration scale (PAS), dysphagia outcome and severity scale (DOSS) and videofluoroscopy dysphagia scale (VDS), and the correlation between swallowing function and respiratory function was analyzed. Results: There were significant differences in pulmonary function among three groups ( P< 0.05). Besides the FEF25,FVC, FIVC between patients with dysphagia after stroke and patients without dysphagia, the FEF75 between patients without dysphagia and normal people (all P> 0.05), there were significant differences in the pairwise comparison of other indicators (all P< 0.05). There were correlations between PAS and MIP ( r= -0.618, P= 0.001),PAS and MEP ( r= -0.410, P= 0.038), PAS and PEF ( r= -0.443, P= 0.024), DOSS and MIP ( r= 0.602, P= 0.000),DOSS and MEP ( r= 0.496, P= 0.005), DOSS and PEF ( r= 0.553, P= 0.002), VDS and MEP ( r= -0.483, P= 0.012),VDS and PEF ( r= -0.494, P= 0.010), respectively. Conclusion: The pulmonary function of dysphagia patients after stroke decrease significantly, and the severity of dysphagia is correlated with the decrease of pulmonary function.

The hepatitis B X protein (HBx) plays a role in the epigenetic regulation of hepatitis B virus (HBV) replication. This study investigated the effects of HBx mutations on HBV transcription and the recruitment of HBx, histone acetyl-transferase P300 and histone deacetylase 1 (HDAC1) to circularized HBV DNA (which resembles covalently closed circular DNA [cccDNA]). Compared with wild type, majority of mutants had lower levels of intracellular HBV RNA (44-77% reduction) and secretory HBsAg (25-81% reduction), and 12 mutants had a reduction in intracellular encapsidated HBV DNA (33-64% reduction). Eight mutants with >70% reduction in HBV RNA and/or HBsAg were selected for chromatin immunoprecipitation analysis. Four HBx mutants with mutations in amino acid residues 55-60 and 121-126 had a lower degree of HBx-cccDNA association than wild type HBx (mean % input: 0.02-0.64% vs. 3.08% in wild type). A reduced association between cccDNA and P300 (mean % input: 0.69-1.81% vs. 3.48% in wild type) and an augmented association with HDAC1 (mean % input: 4.01-14.0% vs. 1.53% in wild type) were detected. HBx amino acid residues 55-60 and 121-126 may play an important role in HBV transcription regulation, via their impeded interaction with cccDNA and altered recruitment of histone modifying enzymes to cccDNA.

Background: Recent studies have focused on the nanoformulations of curcumin to enhance its solubility and bioavailability. The medicinal properties of curcumin-C3 complex, which is a combination of three curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) is less explored., Objective: The aim of this study was to prepare curcumin-C3 encapsulated in chitosan nanoparticles, characterize and evaluate their antioxidant and antibacterial potential., Methods: Ionic gelation method was used to prepare curcumin-C3 nanoparticles and was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy and nanoparticle tracking analysis. In vitro assays were performed to assess drug release, antioxidant and antibacterial activities., Results: Curcumin-C3-chitosan nanoparticle showed an increased entrapment efficiency of >90%, drug release and improved antioxidant potential. Moreover, curcumin-C3-chitosan nanoparticle showed stronger inhibition of Escherichia coli and Staphylococcus aureus., Conclusion: Chitosan is a suitable carrier for curcumin-C3 nanoparticle and can be used as a drug delivery system in the treatment of inflammatory and bacterial diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The specific roles of extracellular polymeric substances (EPS) and how factors influenced EPS's roles during U(VI) immobilization are still unclear. In this study, high content of U with the main form of nanoparticles was detected in EPS, accounting for 10-42% of total U(VI) removal. EPS might be utilized as energy source or even as electron donors when external carbon source was unavailable. The influencing degree of each experimental parameter to uranium (U) removal process was elucidated. The influential priority to U(IV)/U(VI) ratios in sludge was as follows: acetate, U(VI), and nitrate. The influential priority to total EPS contents was as follows: U(VI), nitrate and acetate. The complex interaction mechanism between U(VI) and EPS in the U immobilization process was proposed, which might involve three ways including biosorption, bioreduction and bioprecipitation. These results indicate important and various roles of EPS in U(VI) immobilization.

Multiple exopolysaccharides (EPSs) have been isolated from various organisms in extreme environments and have yielded a variety of activities. The present study evaluated the immunomodulatory capabilities of an EPS (termed PH‑EPS) derived from the fungus Paecilomyces lilacinus PH0016, which was isolated from a tropical and hyperhaline environment in southern China. The macrophage RAW 264.7 cell line was used to investigate the mechanism of PH‑EPS‑induced macrophage activation. The results indicated that RAW 264.7 macrophages were activated by PH‑EPS, in an effect slightly inferior to lipopolysaccharide (LPS), as evidenced by secretion of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α and nitric oxide (NO), and by significantly increased phagocytosis in the cells treated with PH‑EPS. Nuclear factor (NF)‑κB p65 was significantly translocated into the nucleus in the PH‑EPS‑treated cells. In addition, expression of inducible NO synthase (iNOS) and IκB‑α degradation were enhanced in PH‑EPS‑treated cells. The phosphorylation levels of p38, JNK and ERK were also significantly increased in the PH‑EPS‑treated cells. Furthermore, IL‑1β and TNF‑α production was markedly decreased in PH‑EPS‑treated cells when the mitogen‑activated protein kinase (MAPK) pathways were blocked by the inhibitor Dectin‑1 and by antibodies against Toll‑like receptor 4 (TLR4). The present results indicated that PH‑EPS from Paecilomyces lilacinus possessed the capability of activating RAW 264.7 cells via the TLR4/NF‑κB/MAPKs signaling pathway.

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Antibiotic resistance genes (ARGs) are considered to be emerging environmental contaminants. ARGs are frequently detected in municipal solid waste landfill and its leachate. In this study, high-throughput quantitative PCR techniques were used to investigate the dynamics of ARGs during the treatment process of landfill leachate. The results showed that ARGs in leachate were diverse and abundant, and leachate treatment could effectively reduce their abundance; the absolute abundance of ARGs was reduced to 9.2×10 10 copies·L -1 , which was five orders of magnitude less than the abundance of the influent. However, the range and abundance of antibiotic resistance genes in the leachate effluents were still high compared to the natural environment. Therefore, the secondary contamination of ARGs might be caused by leachate being directly discharged into municipal sewage system. In this regard, ecological and environmental risk is an inconvenient truth. Furthermore, strong correlations indicate that heavy metals and mobile genetic elements (MGEs) in landfill leachate might influence the transfer of ARGs.

Background: Computed tomography (CT) is essential for pulmonary nodule detection in diagnosing lung cancer. As deep learning algorithms have recently been regarded as a promising technique in medical fields, we attempt to integrate a well-trained deep learning algorithm to detect and classify pulmonary nodules derived from clinical CT images., Materials and Methods: Open-source data sets and multicenter data sets have been used in this study. A three-dimensional convolutional neural network (CNN) was designed to detect pulmonary nodules and classify them into malignant or benign diseases based on pathologically and laboratory proven results., Results: The sensitivity and specificity of this well-trained model were found to be 84.4% (95% confidence interval [CI], 80.5%-88.3%) and 83.0% (95% CI, 79.5%-86.5%), respectively. Subgroup analysis of smaller nodules (<10 mm) have demonstrated remarkable sensitivity and specificity, similar to that of larger nodules (10-30 mm). Additional model validation was implemented by comparing manual assessments done by different ranks of doctors with those performed by three-dimensional CNN. The results show that the performance of the CNN model was superior to manual assessment., Conclusion: Under the companion diagnostics, the three-dimensional CNN with a deep learning algorithm may assist radiologists in the future by providing accurate and timely information for diagnosing pulmonary nodules in regular clinical practices., Implications for Practice: The three-dimensional convolutional neural network described in this article demonstrated both high sensitivity and high specificity in classifying pulmonary nodules regardless of diameters as well as superiority compared with manual assessment. Although it still warrants further improvement and validation in larger screening cohorts, its clinical application could definitely facilitate and assist doctors in clinical practice., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: Healthcare-associated infections (HAIs) are still a major health threats worldwide. Traditional surveillance methods involving manual surveillance by infection control practitioners (ICPs) for data collection processes are laborious, inefficient, and generate data of variable quality. In this study, we sought to evaluate the impact of surveillance and interaction platform system (SIPS) for HAIs surveillance compared to manual survey in tertiary general hospitals., Methods: A large multi-center study including 21 tertiary general hospitals and 63 wards were performed to evaluate the impact of electronic SIPS for HAIs., Results: We collected 4,098 consecutive patients and found that the hospitals installed with SIPS significantly increased work efficiency of ICPs achieving satisfactory diagnostic performance of HAIs with 0.73 for sensitivity, 0.81 for specificity and 0.81 area under the curve (AUC). However, there were significant heterogeneity own to regions, time of SIPS installation, departments and sample size., Conclusions: SIPS significantly improved ICPs efficiency and HAIs monitoring effectiveness, but there were shortcomings such as untimely maintenance and high cost., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)

Background: Seroclearance of hepatitis B surface antigen (HBsAg) is a potentially achievable target of chronic hepatitis B (CHB). Plasma proteins relevant to HBsAg seroclearance remain undetermined., Methods: We prospectively recruited treatment-naive CHB patients with spontaneous HBsAg seroclearance and matched HBsAg-positive controls. Plasma protein profiling was performed using isobaric tags for relative and absolute quantitation-based proteomics, with the expression of candidate proteins validated in a separate cohort. The predictive value of fibronectin was assessed at 3 years, 1 year (Year -1) before, and at the time (Year 0) of HBsAg seroclearance., Results: Four hundred eighty-seven plasma proteins were identified via proteomics, with 97 proteins showing altered expression. In the verification cohort (n = 90), median plasma fibronectin levels in patients with HBsAg seroclearance was higher than in controls (P = .009). In the longitudinal cohort (n = 164), patients with HBsAg seroclearance, compared with controls, had a higher median fibronectin levels at Year -1 (413.26 vs 227.95 µg/mL) and Year 0 (349.45 vs 208.72 µg/mL) (both P < .001). In patients with an annual HBsAg log reduction >0.5, Year -1 fibronectin level achieved an area under the receiving operator characteristic of 0.884 in predicting HBsAg seroclearance., Conclusions: Using proteomics-based technology, plasma fibronectin may be associated with HBsAg seroclearance and a potential predictor of "functional cure"., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Hepatitis B virus (HBV) is the major risk factor for hepatocellular carcinoma (HCC). The molecular mechanisms underlying HBV-associated HCC pathogenesis is still unclear. Genetic alterations in cancer-related genes have been linked to many human cancers. Here, we aimed to explore genetic alterations in selected cancer-related genes in patients with HBV-associated HCC., Methods: Targeted sequencing was used to analyze six cancer-related genes (PIK3CA, TP53, FAT4, IRF2, HNF4α and ARID1A) in eight pairs of HBV-associated HCC tumors and their adjacent non-tumor tissues. Sanger sequencing, quantitative PCR, Western-blotting and RNAi-mediated gene knockdown were used to further validate findings., Results: Targeted sequencing revealed thirteen non-synonymous mutations, of which 9 (69%) were found in FAT4 and 4 (31%) were found in TP53 genes. Non-synonymous mutations were not found in PIK3CA, IRF2, HNF4α and ARID1A. Among these 13 non-synonymous mutations, 12 (8 in FAT4 and 4 in TP53) were predicted to have deleterious effect on protein function by in silico analysis. For TP53, Y220S, R249S and P250R non-synonymous mutations were solely identified in tumor tissues. Further expression profiling of FAT4 and TP53 on twenty-eight pairs of HCC tumor and non-tumor tissues confirmed significant downregulation of both genes in HCC tumors compared with their non-tumor counterparts (P < 0.001 and P < 0.01, respectively). Functional analysis using RNAi-mediated knockdown of FAT4 revealed an increased cancer cell growth and proliferation, suggesting the putative tumor suppressor role of FAT4 in HCC., Conclusions: This study highlights the importance of FAT4 and TP53 in HCC pathogenesis and identifies new genetic variants that may have potentials for development of precise therapy for HCC.

Background: Most cases of complicated pneumonia in children are caused by pneumococcal infections. Thomsen-Friedenreich antigen (TA) is present on erythrocytes, platelets and glomeruli, and it can be activated during pneumococcal infection. The aim of this study was to investigate the predictive value of TA activation for pneumococcal infection and association with the severity of complicated pneumonia., Materials and Methods: Patients with lobar pneumonia were routinely tested for TA at the Department of Pediatrics, Mackay Memorial Hospital from January 2010 to December 2015. We retrospectively reviewed and analyzed their charts and data including age, sex, etiology of infection, chest tube insertion or video-assisted thoracoscopic surgery, length of hospital stay, TA activation, white blood cell count and level of C reactive protein., Results: A total of 142 children with lobar pneumonia were enrolled, including 35 with empyema, 31 with effusion, 11 with necrotizing pneumonia and four with lung abscess. Streptococcus pneumoniae was the most commonly identified pathogen. Twenty-two patients (15.4%) had activated TA, all of whom were infected with S. pneumoniae. TA activation had 100% specificity and 100% positive predictive value for pneumococcal infection. In the multivariate analysis in lobar pneumonia, TA activation (OR, 15.8; 95% CI, 3.0-83.5; p = 0.001), duration of fever before admission (OR, 1.2; 95% CI, 1.1-1.5; p = 0.013) and initial CRP level (OR, 1.1; 95% CI, 1.0-1.1; p = 0.004) were independent predictors of empyema., Conclusions: TA activation is a specific marker for pneumococcal pneumonia and might indicate higher risk for complicated pneumonia., (Copyright © 2017. Published by Elsevier B.V.)

Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic amphiphiles, is an inexpensive phospholipid substitute to fabricate vesicles with various pharmaceutical applications. Modulating the physicochemical and permeation properties of IPA vesicles are important for carrier designs. Here, we applied molecular dynamics simulations to examine the cholesterol effects on the structures, mechanics, and water permittivity of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium- hexadecylsulfate (DTMA-HS) IPA bilayers. Structural and mechanical analyses indicate that both IPA systems are in gel phase at 298 K. Adding cholesterol induces alkyl chain ordering around the rigid sterol ring and increases the cavity density within the hydrophilic region of both IPA bilayers. Furthermore, the enhanced alkyl chain ordering and the membrane deformation energy induced by cholesterol increase the permeation free energy penalty. In contrast, cholesterol has minor effects on the water local diffusivities within IPA membranes. Overall, the cholesterol reduces the water permittivity of rigid IPA membranes due to the synergistic effects of increased alkyl chain ordering and enhanced membrane mechanical modulus. The results provide molecular insights into the effects of molecular packing and mechanical deformations on the water permittivity of biomimetic IPA membranes, which is critical for designing IPA vesicular carriers.

Background: Campylobacter and Non-typhoidal Salmonella (NTS) are the two most common bacterial pathogens associated with acute gastroenteritis in children. This study aims to elucidate the epidemiology of Campylobacter and NTS gastroenteritis and develop a scoring system to differentiate them., Materials and Methods: This retrospective study enrolled 886 children ≤18 years of age, hospitalized due to acute gastroenteritis with stool culture-proven Campylobacter or NTS infection from July 2012 to December 2015. Pearson's chi-square test and multivariate logistic regression were used to compare clinical manifestations and laboratory data. Receiver operating characteristic curves were plotted to evaluate the scoring system., Results: Seasonality was found in NTS gastroenteritis from May to September, but no seasonality in Campylobacter gastroenteritis. Campylobacter jejuni and Salmonella serogroup B were the most common pathogens. The median ages were 68.2 and 18.5 months and the incidence rates of bacteremia were 0.6% and 7.1% in the Campylobacter and NTS groups, respectively. Salmonella serogroup C2 infection had the highest risk of bacteremia (OR: 5.9, 95% CI: 2.8-12.7, p < 0.001). Multivariate analysis showed significant differences in sex, age, fever, dehydration, immature WBC, CRP and Na between the two groups. A score of ≥2 points indicated Campylobacter gastroenteritis, with sensitivity 75%, specificity 77%. The positive and negative predictive values were of 73.3% and 93.9% after validation., Conclusion: Campylobacter gastroenteritis is associated with older age and male sex, while NTS gastroenteritis is associated with moderate to severe dehydration and bacteremia. Salmonella serogroup C2 infection has the highest risk of bacteremia., (Copyright © 2017. Published by Elsevier B.V.)

To build up an identification method on cardiac glycosides in Taxillus chinensis and its Nerium indicum host, and evaluate the influence on medicine quality from host to T. chinensis, ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass-mass spectrometry(UPLC-Q-TOF-MS/MS)was applied. The samples of T. chinensis(harvested from N. indicum)and its N. indicum host were collected in field. The samples of T. chinensis(harvested from Morus alba)and its M. alba host was taken as control substance. All samples were extracted by ultrasonic extraction in 70% ethanol. Chromatographic separation was performed on an ACQUITY UPLC HSS T3 C&#95;(18)(2.1 mm×100 mm,1.8 μm)column at 40 ℃. Gradient elution was applied, and the mobile phase was consisted of 0.1% formic acid water and acetonitrile. The 0.5 μL of sample solution was injected and the flow rate of the mobile phase was kept at 0.6 mL·min~(-1) in each run. It was done to identify cardiac glycosides and explore the chemical composition correlation in T. chinensis and its N. indicum host by analyzing positive and negative ion mode mass spectrometry data, elemental composition, cardiac glycoside reference substance and searching related literatures. A total of 29 cardiac glycosides were identified, 28 of it belonged to N. indicum host, 5 belonged to T. chinensis(harvested from N. indicum host), none of cardiac glycoside was identified in T. chinensis(harvested from M. alba host). The result could provide a reference in evaluating the influence in T. chinensis medicine quality from host. It was rapid, accurate, and comprehensive to identify cardiac glycosides in T. chinensis and its N. indicum host by UPLC-Q-TOF-MS/MS.

Four laboratory-scale autotrophic nitrogen removal bioreactors were implemented to investigate performance differences and microbial mechanisms under different temperatures (30, 25, 20, and 15℃). The results showed that the reactor performance under 30℃ was higher than others. When the temperature decreased from 30℃ to 25℃, total nitrogen removal efficiency reduced from 73% to 66%, and total nitrogen removal rate from 2.29 kg·(m 3 ·d) -1 to 1.72 kg·(m 3 ·d) -1 . The morphology and particle size of the sludge did not change significantly (SMD:from 80.85 μm to 79.95 μm). When the temperature was 20℃, the total nitrogen removal efficiency reduced to 42%, the total nitrogen removal rate reduced to 1.18 kg·(m 3 ·d) -1 , and the sludge disintegration phenomenon occurred with particle size reduction (SMD:63.21 μm). When the temperature was 15℃, the total nitrogen removal efficiency reduced to 37%, and the total nitrogen removal rate got as low as 1.00 kg·(m 3 ·d) -1 . In addition to that, the reactor operation was difficult. The analysis of microbial community structure showed that the influence of temperature on anaerobic ammonia oxidizing bacteria is greater than that on ammonia oxidizing bacteria. This sensitivity to temperature of the anaerobic ammonia oxidizing bacteria was the main reason for the decreased performance under low temperature conditions.

Microplastics and antibiotic resistance genes (ARGs) are emerging pollutants/contaminants, and are also the research hotspots concerning environmental health in the past few years. To explore the effects of microplastics on ARGs in estuarine sediment, three different microplastics were added to microcosm incubation experiments of sediments. Then, we investigated the persistence, abundance, diversity, and shifts of the ARGs in estuarine sediments by high-throughput quantitative polymerase chain reaction (PCR). The results showed that the microplastics significantly changed the structure of ARGs in the sediments. PVC and PE, which are hard to degrade, had significant effects on the structures and types of ARGs. However, the PVA, which is soluble, reduced the types and persistence of ARGs significantly. The abundance of ARGs in S&#95;PVC, S&#95;PE, and S&#95;PVA were 4.1×10 9 , 8.1×10 9 , and 2.0×10 9 copies·g -1 , respectively. The abundance of ARGs in sediments with added PE almost increased by one order of magnitude, implying that microplastics could significantly increase the abundance of ARGs in sediments. Furthermore, OLS regression analysis showed that ARGs are significantly correlated with transposon and integron, suggesting that mobile genetic elements (MGEs) may promote the transfer and dissemination of ARGs.

Poor wound healing affects millions of people worldwide each year and needs better therapeutic strategies. Synechococcus elongatus PCC 7942 is a naturally occurring photoautotrophic cyanobacterium that can be easily obtained and large-scale expanded. Here, we investigated the therapeutic efficacy of this cyanobacterium in a mouse model of acute burn injury and whether the secretion of extracellular vesicles (EVs), important mediators of cell paracrine activity, is a key mechanism of the cyanobacterium-induced regulation of wound healing. Methods : The effects of Synechococcus elongatus PCC 7942 on burn wound healing in mice under light or dark conditions were evaluated by measuring wound closure rates, histological and immunofluorescence analyses. A series of assays in vivo and in vitro were conducted to assess the impact of the cyanobacterium on angiogenesis. GW4869 was used to interfere with the secretion of EVs by the cyanobacterium and the abilities of the GW4869-pretreated and untreated Synechococcus elongatus PCC 7942 to regulate endothelial angiogenesis were compared. The direct effects of the cyanobacterium-derived EVs ( S. elongatus -EVs) on angiogenesis, wound healing and expressions of a class of pro-inflammatory factors that have regulatory roles in wound healing were also examined. Results : Synechococcus elongatus PCC 7942 treatment under light and dark conditions both significantly promoted angiogenesis and burn wound repair in mice. In vitro , the cyanobacterium enhanced angiogenic activities of endothelial cells, but the effects were markedly blocked by GW4869 pretreatment. S. elongatus -EVs were capable of augmenting endothelial angiogenesis in vitro , and stimulating new blood vessel formation and burn wound healing in mice. The expression of interleukin 6 (IL-6), which has an essential role in angiogenesis during skin wound repair, was induced in wound tissues and wound healing-related cells by S. elongatus -EVs and Synechococcus elongatus PCC 7942. Conclusion : Synechococcus elongatus PCC 7942 has the potential as a promising strategy for therapeutic angiogenesis and wound healing primarily by the delivery of functional EVs, not by its photosynthetic activity. The promotion of IL-6 expression may be a mechanism of the cyanobacterium and its EVs-induced pro-angiogenic and -wound healing effects., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: To evaluate the clinical manifestations, management, and outcomes of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) osteitis/osteomyelitis., Study Design: We reviewed 71 cases of BCG osteitis/osteomyelitis registered in Taiwan's vaccine injury compensation program (VICP) in 1998-2014. Demographic, clinical, laboratory, treatment, and outcome data were compared according to site(s) of infection., Results: Involvement of a long bone of the lower extremity was present in 36.6% of the children, followed by foot bone (23.9%), rib or sternum (15.5%), upper extremity long bone (9.9%), hand bone (7%), multiple bones (4.2%), and vertebrae (2.8%). Children with lower extremity long bone involvement had a longer interval from receipt of BCG vaccine to presentation (median, 16.0 months; P = .02), and those with foot bone infection had higher rates of swelling (94.1%; P = .02) and local tenderness (76.5%; P = .004). Surgical intervention was performed in 70 children, with no significant difference in the number of procedures by site (median, 1.0 procedure per patient). Among the 70 children who received antimicrobial therapy, those with vertebral and multifocal infections had a longer duration of treatment (P < .001) and/or second-line antituberculosis medications (P = .002). Three children with vertebral and multifocal infections had major sequelae with kyphosis or leg length discrepancy. Outcomes were good for children with involvement of the ribs, sternum, and peripheral bones without multifocal involvement. The average time for functional recovery was 6.2 ± 3.9 months., Conclusion: Children with BCG osteitis/osteomyelitis in different bones had distinct presentations and outcomes. Pediatricians should consider BCG bone infection in young vaccinated children with insidious onset of signs and symptoms, and consider affected site(s) in the management plan., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Lattice corneal dystrophy (LCD) is related to the denaturation of transforming growth factor-β-induced protein (TGFBIp). Autophagic degradation of the denatured proteins by macrophages is one pathway to remove the denatured proteins. Thus, we investigated the role of autophagy in the degradation of mutant (MU) TGFBIp in macrophages., Methods: Corneas from participants were observed by slit-lamp photography and subjected to histopathologic and genetic analysis. Wild-type (WT) and MU TGFBIp were recombined and expressed. Macrophages from MU participants were isolated and cocultured with the recombinant TGFBIp. Colocalization of the two molecules was observed by immunofluorescent microscopy. Enzyme-linked immunosorbent assay, Western blotting, and flow cytometry were used to detect changes in molecule expression related to the phenotype and autophagy process., Results: Fourteen members from a family of 25 were identified as LCD sufferers. Significant TGFBIp aggregates and macrophage infiltration were found only in the corneas of LCD sufferers. Marker accumulation of TGFBIp was found in macrophages exposed to MU TGFBIp even at 5 hours after MU TGFBIp was withdrawn. High expressions of CD68 and CD36 were found in macrophages exposed to WT TGFBIp, but not to MU TGFBIp. Impaired autophagic flux due to defective autophagosome fusion to lysosomes was found in macrophages exposed to MU TGFBIp. Blockage of the autophagic process suppressed the expression of CD68 and CD36 in macrophages exposed to WT TGFBIp to levels similar to those found in macrophages exposed to MU TGFBIp., Conclusions: Our results suggested that reversion of the defective autophagic process in macrophages may be a therapeutic strategy for patients with LCD.

Background: Ancient medical practitioners used to encourage dietary supplements and herbal medicine for the treatment of type 2 diabetes mellitus (T2DM). Ginger (Zingiber officinale), is a nontoxic spice with negligible side effects, and is considered safe by the food and drug administration. In this analysis, we aimed to systematically compare fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) at baseline versus at follow-up in T2DM patients who consumed and who did not consume ginger., Methods: A literature search was carried out through MEDLINE, Embase, the Cochrane Central, and www.ClinicalTrials.gov for English-published trials comparing glucose parameters in T2DM patients who were assigned to ginger consumption versus a control group. All the participants were patients with T2DM who were either assigned to ginger therapy (1600- 4000 mg daily) or to a control group. FBS and HbA1c were assessed in the ginger and control groups, respectively, from baseline to follow-up to observe any significant change. Weight mean difference (WMD) with 95% confidence intervals (CI) was calculated to represent the analysis which was carried out by the RevMan 5.3 software., Results: Eight randomized trials consisting of a total number of 454 participants with T2DM were included in this analysis. At first, FBS was compared in patients with T2DM from baseline prior to ginger consumption until follow-up after ginger consumption. The results showed no significant difference in FBS (WMD: 1.38, 95% CI: [-0.53-3.30]; P = .16). For the T2DM patients who did not consume ginger, no significant difference in FBS was observed (WMD: -0.27, 95% CI: [-5.09-4.54]; P = .91). However, a significantly improved HbA1c from baseline to follow-up was observed in those participants with ginger consumption (WMD: 0.46, 95% CI: [0.09-0.84]; P = .02) whereas in the control group, no significant difference in HbA1c was observed (WMD: -0.23, 95% CI: [-0.60-0.14]; P = .22)., Conclusion: This analysis involving patients with T2DM showed no significant difference in FBS with ginger consumption. However, dietary ginger significantly improved HbA1c from baseline to follow-up showing that this natural medicine might have an impact on glucose control over a longer period of time in patients with T2DM.

Objective: To explore the preventive effect and possible molecular mechanism of dietary supplementation of N-carbamylglutamate (NCG) in the implantation of carbon disulfide (CS(2)) into embryo implantation disorders. Methods: embryo implantation disorder model was established by single intraperitoneal exposure to CS(2) on the 3rd, 4th, and 5th days after pregnancy. Endometrial tissues were collected for 24h after exposure to CS(2) for western-blot and immunohistochemical staining. Results: The number of embryo implantation was increased in NCG+CS(2) group, compared with CS(2) alone group. Day 4 of pregnancy when CS(2)-exposed after 24 h, the expression of pAKT protein in NCG+CS(2) group was significantly increased ( P <0.05), the expression level of pAMPK protein in NCG+CS(2) group was significantly decreased, compared with CS(2) alone group, respectively. Immunohistochemical results showed that pAKT, pAMPK, AKT and AMPK proteins were expressed in luminal epithelial cells, glandular epithelial cells and stromal cells of endometrium; Day 4 of pregnancy when CS(2)-exposed after 24 h, deep staining of ATK and pAKT protein in NCG+CS(2) group, the AMPK and pAMPK protein staining became lighter. Conclusion: Dietary supplementation of NCG can interfere with the embryo loss induced by CS(2) by altering the total amount of AKT/AMPK molecules.

Background: Ageing is a risk factor for both coronary artery disease (CAD) and reduced renal function (RRF), and it is also associated with poor prognosis in patients with CAD or RRF. However, little is known about whether the impact of RRF on clinical outcomes are different in CAD patients at different age groups. This study aimed to investigate whether ageing influences the effect of RRF on long-term risk of death in patients with CAD., Methods: A retrospective analysis was conducted using data from a single-center cohort study. Three thousand and two consecutive patients with CAD confirmed by coronary angiography were enrolled. RRF was defined as an estimated glomerular filtration rate (eGFR) of less than 60 ml/min. The primary endpoint in this study was all-cause mortality., Results: The mean follow-up time was 29.1 ± 12.5 months and death events occurred in 275 cases (all-cause mortality: 9.2%). The correlation analysis revealed a negative correlation between eGFR and age (r = - 0.386, P < 0.001). Comparing the younger group (age ≤ 59) with the elderly one (age ≥ 70), the prevalence of RRF increased from 5.9 to 27.5%. Multivariable Cox regression revealed that RRF was independently associated with all-cause mortality in all age groups, and the relative risks in older patients were lower than those in younger ones (age ≤ 59 vs. age 60-69 vs. age ≥ 70: hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.04-6.37 vs. HR 2.00, 95% CI 1.17-3.42 vs. HR 1.46, 95% CI 1.06-2.02). There was a significant trend for HRs for all-cause mortality according to the interaction terms for RRF and age group (RRF*age [≤59] vs. RRF*age [60-69] vs. RRF*age [≥70]: HR 1.00[reference] vs. HR 0.60, 95% CI 0.23-1.54 vs. HR 0.32, 95% CI 0.14-0.75; P for trend = 0.010)., Conclusions: RRF may have different impacts on clinical outcomes in CAD patients at different age groups. The association of RRF with the risk of all-cause mortality was attenuated with ageing.