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Aims/Introduction Diabetic peripheral neuropathy is a common diabetes‐related microvascular complication. The relationship between peripheral nerve function and glucose variability is unclear. We investigated the association of glucose variability with subclinical diabetic polyneuropathy in a large‐scale sample of patients with type 2 diabetes. Materials and Methods We enrolled 509 individuals with type 2 diabetes who were screened for diabetic peripheral neuropathy and monitored using a continuous glucose monitoring system. Multiple glycemic variability parameters, including the mean amplitude of glycemic excursions, glucose standard deviation (SDgluc) and glucose coefficient of variation were calculated from 3‐day glucose profiles obtained from continuous glucose monitoring. All participants underwent nerve conduction studies, and the composite Z‐scores for nerve conduction parameters were calculated. Results Multivariate logistic regression analyses showed that SDgluc and the conventional risk factor hemoglobin A1c (HbA1c) were independently associated with abnormal nerve function, and the corresponding odds ratios (95% confidence interval) were 1.198 (1.027–1.397, SDgluc) and 1.182 (1.061–1.316, HbA1c), respectively. The composite Z‐score of nerve conduction velocity and response amplitude obviously decreased with greater SDgluc, and the composite Z‐score of distal latency significantly increased with increasing tertiles of SDgluc (all P trend

The lockdown due to COVID-19 created a rare opportunity to examine the nonlinear responses of secondary aerosols, which are formed through atmospheric oxidation of gaseous precursors, to intensive precursor emission reductions. Based on unique observational data sets from six supersites in eastern China during 2019-2021, we found that the lockdown caused considerable decreases (32-61%) in different secondary aerosol components in the study region because of similar-degree precursor reductions. However, due to insufficient combustion-related volatile organic compound (VOC) reduction, odd oxygen (Ox = O3 + NO2) concentration, an indicator of the extent of photochemical processing, showed little change and did not promote more decreases in secondary aerosols. We also found that the Chinese provinces and international cities that experienced reduced Ox during the lockdown usually gained a greater simultaneous PM2.5 decrease than other provinces and cities with an increased Ox. Therefore, we argue that strict VOC control in winter, which has been largely ignored so far, is critical in future policies to mitigate winter haze more efficiently by reducing Ox simultaneously.

Objective: Patients with recurrent respiratory papillomatosis (RRP) have significant vocal dysfunction which affects their performance at work. This study aimed to evaluate voice-related work productivity before and after ablative treatment for RRP. Methods: This is a prospective case series conducted at 2 academic laryngology outpatient clinics. Adult employed patients with RRP completed the Work Productivity & Activity Impairment instrument (WPAI), Voice Handicap Index (VHI-10), WorkHoarse, Hospital Anxiety and Depression Scale (HADS), and a demographics questionnaire immediately before and 1 month after ablative treatment of papilloma. The primary outcome measure was the change in work productivity impairment domain of the WPAI, and changes in ratings before and after ablation were compared using a Wilcoxon Signed-Rank test. Results: The 32 participants (mean age 45, 84% male) had a median (interquartile range) voice-related work productivity impairment score of 48.8% (30.0) at baseline which was improved to 5.0% (10.0) at 1 month after surgical ablation of papillomata (difference 30.0% (30.0) improvement). For the secondary outcome measures, there were significant improvements in VHI-10 ( P Conclusion: Patients with RRP experience significant voice-related work productivity impairment, and ablation of papillomata significantly improves work productivity.

An all-in-one nanosensor was developed for the magnetic enrichment and ratiometric surface-enhanced Raman scattering (SERS) detection of Escherichia coli (E. coli). The all-in-one nanosensor was constructed through the chemical integration of four components into a single nanoparticle, which include a manganese ferrite nanoparticle serving as the magnetic core, a thin silver shell as the SERS substrate, a self-assembled layer of 4-mercaptobenzoic acid (MBA) molecules as the SERS internal standard, and a MBA-conjugated layer of aptamer sequences as the capture probe of E. coli. In the detection of E. coli in food, the target cells were first captured by the nanosensors and magnetically enriched in a short time of 15 min, and then the ratiometric SERS was performed through the Raman intensity ratio between two specific SERS peaks produced by the captured E. coli and the internal MBA. The pre-concentration and ratiometry enabled the nanosensor to detect E. coli with a detection limit down to 10 CFU/mL. The all-in-one nanosensor was successfully applied for the detection of E. coli in various liquid foods including milk, juice, tea, and coffee, with recoveries ranging from 89 to 110% and relative standard deviation lower than 1.7%. In comparison with the previous sandwich strategy adopted by most SERS sensors, this nanosensor endowed with an easier use and a lower cost is more sensitive and reproducible, leading to a great potential in practical applications.

Importance. Acupuncture is an effective treatment for stroke, especially in the aspect of motor deficit. Many brain imaging studies of acupuncture have found significant changes in brain function after acupuncture treatment in order to reveal its underlying mechanisms in regulating neural plasticity. However, no definite consensus has been reached. Objective. To analyze the pattern of intrinsic brain activity variability that is altered by acupuncture compared with conventional treatment in stroke patients with motor dysfunction, thus providing the mechanism of stroke treatment by acupuncture. Methods. Chinese and English articles published up to May 2020 were searched in the PubMed, Web of Science, EMBASE, and Cochrane Library databases, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Database. We only included randomized controlled trials (RCTs) using resting-state fMRI to observe the effect of acupuncture on stroke patients with motor dysfunction. R software was used to analyze the continuous variables, and Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) was used to perform an analysis of fMRI data. Findings. A total of 7 studies comprising 143 patients in the treatment group and 138 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps the healing process of motor dysfunction in stroke patients and exhibits hyperactivation in the bilateral basal ganglia and insula and hypoactivation in motor-related areas (especially bilateral BA6 and left BA4). Conclusion. Acupuncture plays a role in promoting neuroplasticity in subcortical regions that are commonly affected by stroke and cortical motor areas that may compensate for motor deficits, which may provide a possible mechanism underlying the therapeutic effect of acupuncture.

Marine microbes provide an important resource to discover new chemical compounds with biological activities beneficial to drug discovery. In our study, two new polyene macrolides, pyranpolyenolides A (1) and B (2), and one new natural cyclic peptide (9), together with two known polyenes (7 and 8) and three known cyclic peptides (10-12), were isolated from a culture of the marine Streptomyces sp. MS110128. In addition, four new polyene macrolides, pyranpolyenolides C-F (3-6), were identified as olefin geometric isomers that were most likely produced by photochemical conversion during the cultivation or isolation procedures. The pyranpolyenolides are 32-membered macrolides endowed with a conjugated tetraene and several pairs of 1,3-dihydroxyl groups. Pyranpolyenolides that contain a hydropyran group have not been previously reported. Four cyclic peptides (9-12) showed significant activities against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant S. aureus with supporting MIC values ranging from 0.025 to 1.25 μg/mL. These cyclic peptides containing piperazic moieties showed moderate activities with MIC values of 12.5 μg/mL against Bacille Calmette Guerin (BCG), an attenuated form of the bovine. Additionally, cyclic peptide 12 showed moderate antifungal activity against Candida albicans with an MIC value of 12.5 μg/mL. KEY POINTS: • Discovery of new polyenes and cyclic peptides from a marine-derived Actinomycete. • Cyclic peptides containing piperazic moieties exhibited good antibacterial activity.

Crystals have been widely used in the pharmaceutical industry, structural elucidation, and other biomedical fields. Different polymorphs of one compound possess distinct physical and chemical prope...

The hexanucleotide repeat (GGGGCC) expansion in C9orf72 is accounted for a large proportion of the genetic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The hypotheses of h...

Aims Pre‐existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease‐2019 (COVID‐19) outcomes. However, data on outcomes of COVID‐19 among people with pre‐existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre‐existing HF with COVID‐19 outcomes. Methods and results A retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID‐19 diagnosis among Veterans with and without pre‐existing diagnosis of HF. Cox‐regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID‐19, 6148 had pre‐existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID‐19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61–2.17) and 1.79 (1.66–1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15–1.64) and 1.27 (1.16–1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants. Conclusions Patients with COVID‐19 and pre‐existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin‐converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.

An efficient and high-yielding synthetic method for the preparation of vildagliptin via four steps is reported. The process starts from L-proline and involves a successful reaction with chloroacetyl chloride in tetrahydrofuran to afford ( S)-1-(2-chloroacetyl)pyrrolidine-2-carboxylic acid, followed by a reaction with acetonitrile in the presence of sulfuric acid to give ( S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile. This is then reacted with 3-aminoadamantanol to give vildagliptin. 3-Aminoadamantanol is prepared from 1-aminoadamantane hydrochloride via oxidation with sulfuric acid/nitric acid and boric acid as the catalyst followed by ethanol extraction. The overall yield is 95%.

This cross-sectional study examined nurse practitioners’ (NPs’) intimate partner and sexual violence screening behaviors and identified associated factors. A survey invitation was mailed to 1000 primary care NPs, and the final sample included 170 NPs. The mean rate of violence screening was 18.9%. Of NPs who responded, 56% reported screening “almost none” of the female patients for violence during the past 3 months. Main concerns included time required to screen (32.3%) and disruption to clinic operations (18.3%). Nearly 80% of the NPs reported a need for additional training as a barrier to intimate partner and sexual violence screening.

Omega-3 fatty acids plus vitamin (e.g. vitamin D and E) may be beneficial to treat gestational diabetes mellitus (GDM), and we aimed to study the influence of omega-3 fatty acids plus vitamin versus placebo on the treatment efficacy of GDM.We searched the databases including PubMed, Embase, and the Cochrane Central Register of Controlled Trials, and randomized controlled trials (RCTs) assessing the influence of omega-3 fatty acids and vitamins combination supplementation versus placebo on metabolic status of GDM were included.Five RCTs were included in the meta-analysis. Compared with control intervention for women with GDM or prediabetes, omega-3 fatty acids plus vitamin substantially reduced fasting plasma glucose (FPG, mean difference [MD] = -11.25; 95% confidence intervals [CI] = -13.73 to -8.77;The supplementation of omega-3 fatty acids in combination with vitamin D or E can improve glycemic control, alleviate oxidative stress, and reduce triglycerides, but had no effects on total cholesterol, preterm delivery or macrosomia4000 g in women with GDM or prediabetes.

Proteins with different micropatterns have various applications in biosensing, structural analysis, and other biomedical fields. However, processing of micropatterns on single protein crystals remains a challenge due to the fragility of protein molecules. In this work, we studied femtosecond laser processing on single hen egg white lysozyme protein crystals. Optimized laser parameters were found to achieve micropatterning without cracking of protein crystals. The ablation morphology dependence on the laser fluence and the pulse number was discussed to control the processing results. Under a laser fluence higher than 1 J/cm2, the ablation hole was formed. While multipulses with fluence lower than the ablation threshold were applied, the foaming area was observed due to the denaturation of protein. The numerical simulation shows that the ablation results were influenced by the ionization and energy deposition process. Micropatterns including lines, areas, and microarrays can be processed with a minimum size of 2 μm. Processed patterns on the crystal surface can be used for biosensing microarrays and the enhancement of crystal growth. The microprocessing method proposed in this study has potential applications in different fields including biodevices and biomedicine.

Background An accurate assessment of the severity and prognosis of sepsis, especially septic shock, is vital for the tailored treatment of this condition. miRNA participates in the inflammatory response and cell apoptosis and regulates inflammation-related signaling pathways. Immune disorders often accompany sepsis. Since serum miRNA expression is superior to traditional biological markers in terms of sensitivity and specificity, its role in the assessment of sepsis has increasingly been recognized. Methods Serum miRNAs were extracted from septic patients and healthy individuals by using the ultracentrifugation method. The differential expressions of miRNAs in the serum samples were detected by high-throughput sequencing technology. The differentially expressed miRNAs between the two groups were analyzed by bioinformatics. The quantitative polymerase chain reaction real-time polymerase chain reaction (qRT-PCR) was used to amplify the sample size to verify the results and to screen the highly-expressed miR206 in septic patients. Subsequently, serum samples were collected from 63 septic patients, and 30 patients with septic shock and qRT-PCR were performed to analyze the expression of miR-206. These 93 patients were divided into the miR-206 low-expression group and miR-206 high-expression group according to miR206 expression level. The potential correlations between the miR-206 expression and the clinical data were analyzed by using SPSS 25.0. Results Serum miRNA expression significantly differed between septic patients and healthy individuals. High-throughput sequencing results showed that, compared with those in healthy individuals, 29 miRNA molecules were down-regulated, and 25 molecules were up-regulated in the serum samples of septic patients. qRT-PCR identified the significantly up-regulated miR-206 in septic patients. qRT-PCR also showed significantly higher miR-206 expression levels in patients with septic shock than in septic patients. Furthermore, we observed a significantly longer prothrombin time and activated partial thromboplastin time, and significantly higher SOFA score, APACHE-II score, and in-hospital mortality rate. miR-206 was positively correlated with SOFA sore and APACHE-II score. Conclusions Serum miR-206 expression is positively correlated with the severity and prognosis of sepsis. Thus, it may be a potential biomarker for assessing the severity and prognosis of sepsis, although the specific mechanism warrants further investigations.

Background. Stroke can lead to disruption of the whole-brain network in patients. Acupuncture can modulate the functional network on a large-scale level in healthy individuals. However, whether and how acupuncture can make a potential impact on the disrupted whole-brain network after ischemic stroke remains elusive. Methods. 26 stroke patients with a right hemispheric subcortical infarct were recruited. We gathered the functional magnetic resonance imaging (fMRI) from patients with stroke and healthy controls in the resting state and after acupuncture intervention, to investigate the instant alterations of the large-scale functional networks. The graph theory analysis was applied using the GRETNA and SPM12 software to construct the whole-brain network and yield the small-world parameters and network efficiency. Results. Compared with the healthy subjects, the stroke patients had a decreased normalized small-worldness (σ), global efficiency (Eg), and the mean local efficiency (Eloc) of the whole-brain network in the resting state. There was a correlation between the duration after stroke onset and Eloc. Acupuncture improved the patients’ clustering coefficient (Cp) and Eloc but did not make a significant impact on the σ and Eg. The postacupuncture variables of the whole-brain network had no association with the time of onset. Conclusion. The poststroke whole-brain network tended to a random network with reduced network efficiency. Acupuncture was able to modulate the disrupted patterns of the whole-brain network following the subcortical ischemic stroke. Our findings shed light on the potential mechanisms of the functional reorganization on poststroke brain networks involving acupuncture intervention from a large-scale perspective.

Glioblastoma multiforme (GBM) is a very serious mortality of central nervous system cancer. The microarray data from GSE2223, GSE4058, GSE4290, GSE13276, GSE68848 and GSE70231 (389 GBM tumour and 67 normal tissues) and the RNA‐seq data from TCGA‐GBM dataset (169 GBM and five normal samples) were chosen to find differentially expressed genes (DEGs). RRA (Robust rank aggregation) method was used to integrate seven datasets and calculate 133 DEGs (82 up‐regulated and 51 down‐regulated genes). Subsequently, through the PPI (protein‐protein interaction) network and MCODE/ cytoHubba methods, we finally filtered out ten hub genes, including FOXM1, CDK4, TOP2A, RRM2, MYBL2, MCM2, CDC20, CCNB2, MYC and EZH2, from the whole network. Functional enrichment analyses of DEGs were conducted to show that these hub genes were enriched in various cancer‐related functions and pathways significantly. We also selected CCNB2, CDC20 and MYBL2 as core biomarkers, and further validated them in CGGA, HPA and CCLE database, suggesting that these three core hub genes may be involved in the origin of GBM. All these potential biomarkers for GBM might be helpful for illustrating the important role of molecular mechanisms of tumorigenesis in the diagnosis, prognosis and targeted therapy of GBM cancer.

PURPOSE To investigate the prevalence of preoperative cataract surgery testing and consultation at a single United States teaching hospital. SETTING Academic-affiliated Veterans Affairs Medical Center. DESIGN Retrospective chart review. METHODS This study included patients who received cataract surgery from 2014 to 2018. For patients with bilateral cataracts, the second surgery was excluded to ensure independent selection. Charlson Comorbidity Index (CCI) scores and heart disease status were recorded. The outcomes of interest were preoperative testing, such as complete blood count, chemistry panel, and echocardiography, and consultation (office visits to non-ophthalmologists) during the period between the date the decision was made to proceed with surgery and the cataract surgery date. RESULTS For this study 1320 charts were reviewed; 1257 (95.2%) patients met the study criteria. The mean CCI score was 1.7; 42.0% (528/1257) had heart disease. The prevalence of preoperative testing was 0.08% (1/1257). The prevalence of preoperative consultation was 4.2% (53/1257); 86.8% (46/53) of patients received cardiology consultation; 17.0% (9/53) pulmonology; and 15.1% (8/53) primary care. Of the patients who received cardiac consultation, 63.0% (29/46) had heart disease; the remaining had an electrocardiogram abnormality. CONCLUSIONS There was a low prevalence of preoperative testing and consultation for cataract surgery at this teaching hospital. Further studies using medical record data are needed to assess the current rates and the role of preoperative testing and consultation for cataract surgery patients.

Numerous valuable studies on electron dynamics have focussed on the extraordinary properties of molybdenum disulfide (MoS2); however, most of them were confined to the level below the damage threshold. Here the electron dynamics of MoS2 under intense ultrafast laser irradiation was investigated by experiments and simulations. Two kinds of ablation mechanisms were revealed, which led to two distinct types of electron dynamics and final ablation morphology. At a higher fluence, the emergence of superheated liquid induced a dramatic change in the transient reflectivity and micro-honeycomb structures. At a lower fluence, the material was just removed by sublimation, and the ablation structure was relatively flat. X-ray photoelectron spectroscopic (XPS) measurements demonstrated that thermal decomposition only occurred at the higher fluence. Furthermore, a theoretical model was developed to deeply reveal the ultrafast dynamics of MoS2 ablation. The simulation results were in good agreement with the temporal and spatial reflectivity distribution obtained from the experiment. The electron and lattice temperature evolution was also obtained to prove the ablation mechanism. Our results revealed ultrafast dynamics of MoS2 above the damage threshold and are helpful for understanding the interaction mechanism between MoS2 and intense ultrafast lasers, as well as for MoS2 processing applications., Optoelectronics: Digging into molybdenum disulfide Ultrafast damage-causing laser pulses affect bulk molybdenum disulfide differently depending on their energy per area, revealing further insight into the ultrafast electron dynamics. The research group of Lan Jiang from Beijing Institute of Technology, in cooperation with Tianhong Cui of University of Minnesota, has predicted and examined what happened to molybdenum disulfide on electron and lattice level when intense femtosecond laser pulses irradiate. Lower damage-causing energies per area, known as fluences, removed material through inducing a solid-to-gas transition. Higher fluences caused superheating, liquidation, and the formation of nanocracks and nanoridges. Tests on electron dynamics obtained by the materials’ reflectivity with different fluences were followed by theoretical simulations, which further helped to reveal the electron and lattice temperature evolution. The findings further understandings for laser processing of molybdenum disulfide and for its use in optoelectronics.

Maintenance of regulatory T (Treg) cells is crucial for the regulatory function of Treg cells in immune homeostasis and self-tolerance; however, the detailed underlying mechanisms remain elusive. In the current study, we found that the cytokine suppressor CIS (cytokine induced SH-2 protein) is required for maintenance of Treg cell identity. Mice with Treg-specific Cis-deficiency displayed aggravated experimental allergic asthma, and in adulthood, developed splenomegaly, lymphadenopathy and spontaneous eosinophilic airway inflammation, accompanied by accumulation of effector memory helper T (TH) cells. Cis-deficiency led to the loss of Foxp3 expression and the decrease in suppressive function of Treg cells. Cis-deficient Treg cells expressed TH2 cell signature genes, Gata3, Irf4 and Il4, and excessive interleukin-4-signal transducer and activator of transcription 6 (IL-4-STAT6) signals resulted in repressive chromatin modification in the Foxp3 locus and permissive modification in the Il4 loci. In vitro, blockade of IL-4 restored the expression of Foxp3 and the suppressive function of inducible Treg (iTreg) cells. Thus, we identified a novel feedback loop in stabilization of Treg cells and suppression of TH2-type inflammation in a Treg-intrinsic manner.

Increasing attention has recently been focused on complex symbiotic associations, for instance coral and its symbionts. Sea cucumber, harboring diverse fungi, has also attracted more and more attention for their functional diversity. Here, secondary metabolites produced by Chaetomium globosum associated with sea cucumber, Apostichopus japonicus, were investigated using gene mining with third-generation sequencing technology (PacBio SMRT). Nine compounds, including one new compound cytoglobosin X (1), were isolated from cultures of Chaetomium globosum. Compound 1 was identified based on NMR data, HRESIMS, and ECD, and the absolute configurations were identified as 3S, 4R, 7S, 8R, 9R, 16S, 19S, 20S, and 23S. In an antimicrobial assay, compound 4 showed moderate activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus with MICs of 47.3 and 94.6 μM, respectively. Our results suggest that the microbiomes associated with sea cucumber could be an important resource for biodiversity and structural novelty, and the bioactive compounds may protect the host from pathogen microbial.

Invasive group B Streptococcus (GBS) remains a leading cause of illness and death among infants globally. We conducted prospective and retrospective laboratory-based surveillance of GBS-positive cultures from infants

CPVL (Carboxypeptidase, vitellogenic-like) is a serine carboxypeptidase which was first characterized in human macrophages. However, the function of CPVL remains unclear in a variety of tumors. The quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) assays were utilized to measure the CPVL expression. CPVL was significantly upregulated in glioma cells and tissues compared to normal cells and tissues, respectively. Moreover, high CPVL expression was correlated with advanced clinical grade and poor prognosis. Silencing of CPVL promoted glioma cell apoptosis, inhibited cell proliferation and tumorigenicity in vitro and in vivo. Ingenuity Pathway Analysis (IPA) demonstrated that CPVL silencing activated the IFN-γ/STAT1 signaling pathway, thereby inducing glioma cell apoptosis. Mechnistically, immunopurification, mass spectrometry, immunoprecipitation (IP), and glutathione S-transferase (GST) pull-down experiments elucidated that CPVL physically interacts with Bruton's tyrosine kinase (BTK) and downregulates the STAT1 phosphorylation through promoting p300-mediated STAT1 acetylation. For the first time, our findings revealed the crucial role of CPVL in promoting the progression of glioma through suppressing STAT1 phosphorylation. CPVL might serve as a potential prognostic biomarker and therapeutic target for the treatment of glioma.

Background Prior studies have identified lower mortality in Black Veterans compared with White Veterans after hospitalization for common medical conditions, but these studies adjusted for comorbid conditions identified in administrative claims. Objectives The objectives of this study were to compare mortality for non-Hispanic White (hereafter, "White"), non-Hispanic Black (hereafter, "Black"), and Hispanic Veterans hospitalized for heart failure (HF) and pneumonia and determine whether observed mortality differences varied according to whether claims-based comorbid conditions and/or clinical variables were included in risk-adjustment models. Research design This was an observational study. Subjects The study cohort included 143,520 admissions for HF and 127,782 admissions for pneumonia for Veterans hospitalized in 132 Veterans Health Administration (VA) Medical Centers between January 2009 and September 2015. Measures The primary independent variable was racial/ethnic group (ie, Black, Hispanic, and non-Hispanic White), and the outcome was all-cause mortality 30 days following admission. To compare mortality by race/ethnicity, we used logistic regression models that included different combinations of claims-based, clinical, and sociodemographic variables. For each model, we estimated the average marginal effect (AME) for Black and Hispanic Veterans relative to White Veterans. Results Among the 143,520 (127,782) hospitalizations for HF (pneumonia), the average patient age was 71.6 (70.9) years and 98.4% (97.1%) were male. The unadjusted 30-day mortality rates for HF (pneumonia) were 7.2% (11.0%) for White, 4.1% (10.4%) for Black and 8.4% (16.9%) for Hispanic Veterans. Relative to White Veterans, when only claims-based variables were used for risk adjustment, the AME (95% confidence interval) for the HF [pneumonia] cohort was -2.17 (-2.45, -1.89) [0.08 (-0.41, 0.58)] for Black Veterans and 1.32 (0.49, 2.15) [4.51 (3.65, 5.38)] for Hispanic Veterans. When clinical variables were incorporated in addition to claims-based ones, the AME, relative to White Veterans, for the HF [pneumonia] cohort was -1.57 (-1.88, -1.27) [-0.83 (-1.31, -0.36)] for Black Veterans and 1.50 (0.71, 2.30) [3.30 (2.49, 4.11)] for Hispanic Veterans. Conclusions Compared with White Veterans, Black Veterans had lower mortality, and Hispanic Veterans had higher mortality for HF and pneumonia. The inclusion of clinical variables into risk-adjustment models impacted the magnitude of racial/ethnic differences in mortality following hospitalization. Future studies examining racial/ethnic disparities should consider including clinical variables for risk adjustment.

BackgroundAllergic rhinitis is a disease associated with impaired quality of life and heredity. This study aimed to investigate the association of allergic rhinitis (AR) in preschool children with exposure to indoor environment-related factors early in life. MethodsIn August 2019, we implemented a study among 2020 preschool children in Urumqi City using a case-control design. The study included parental reports for the occurrence of AR in children, parental history of respiratory disease, and indoor environmental correlates of maternal exposure from 1 year prior to pregnancy until the child's age of 0-1 years.ResultsMode of birth (caesarean section) (OR=1.31, 95%CI=1.02~1.67), father with AR (OR=2.67, 95%CI=2.08~3.44), mother with AR (OR=3.70, 95%CI=2.88~4.74), mother with asthma (OR=3.11, 95%CI=1.18~8.20), and mother with newly purchased furniture in the parents' residence during pregnancy (OR=1.49, 95%CI=1.03~2.14) were risk factors for AR in children. ConclusionsThe focus of allergic rhinitis should should be on children with a family history of AR and asthma and caesarean delivery. Primary prevention efforts for AR in preschool children are avoiding exposure of children to indoor environmental hazardous factors early in life.

COPD, a chronic obstructive pulmonary disease, is one of the leading causes of death worldwide. Clinical studies and research in rodent models demonstrated that failure of repair mechanisms to cope with increased ROS and inflammation in the lung leads to COPD. Despite this progress, the molecular mechanisms underlying the development of COPD remain poorly understood, resulting in a lack of effective treatments. Thus, an informative, simple model is highly valued and desired. Recently, the cigarette smoke-induced Drosophila COPD model showed a complex set of pathological phenotypes that resemble those seen in human COPD patients. The Drosophila trachea has been used as a premier model to reveal the mechanisms of tube morphogenesis. The association of these mechanisms to structural changes in COPD can be analyzed by using Drosophila trachea. Additionally, the timeline of structural damage, ROS, and inflammation can be studied in live organisms using fluorescently-tagged proteins. The related function of human COPD genes identified by GWAS can be screened using respective fly homologs. Finally, the Drosophila trachea can be used as a high-throughput drug screening platform to identify novel treatments for COPD. Therefore, Drosophila trachea is an excellent model that is complementary to rodent COPD models.

In this study, femtosecond laser double pulses were tested to improve their nickel ablation efficiency. The experimental results indicated that compared with single pulses, double pulses with different delay times generated craters with larger diameters and depths. The results obtained for three sets of double pulses with different energy ratios indicated that double pulses with an energy ratio of 1:9 had the highest ablation efficiency, followed by those with energy ratios of 2:8 and 5:5. The double pulses with the aforementioned three energy ratios achieved the maximum ablation efficiency when the delay time was 3–4 ps. Compared with single pulses, double pulses with an energy ratio of 1:9 generated craters with an up to 34% greater depth and up to 14% larger diameter. In addition, an interference effect was observed with a double pulse delay time of 0 ps, which has seldom been reported in the literature. The double pulses were simulated using the two-temperature model. The simulation results indicated that double pulses with an energy ratio of 1:9 with a delay time of 4 ps can perform the strongest ablation. These simulation results are in line with the experimental results.

Importance A disordered voice can affect an individual across both work and non-work-related life domains. There is insufficient research testing on the effect of spasmodic dysphonia or its treatment with botulinum neurotoxin (BoNT) injections on work productivity. Objective To assess whether employed patients with spasmodic dysphonia experience voice-related work productivity impairment before BoNT injection, and had a 10% or greater improvement in productivity 1 month after treatment with BoNT injection. Design, setting, and particpants This prospective case series carried out in 2 laryngology outpatient clinics from November 1, 2015, to August 30, 2018 included a consecutive sample of adult employed patients diagnosed with spasmodic dysphonia. Analysis was conducted between November 1, 2015, to July 31, 2018. Exposures Treatment with BoNT injection into the intrinsic laryngeal musculature. Main outcomes and measures Eligible participants completed the following validated outcomes instruments immediately before and 1 month after outpatient laryngeal BoNT injection: the Work Productivity and Activity Impairment instrument (WPAI), Voice Handicap Index (VHI), and WorkHoarse. Demographic, comorbidity, and occupational voice use data were also collected at baseline. The changes in outcome measures (primary, WPAI Work Productivity Impairment domain) were tested using a paired 2-tailed t test. Exploratory subgroup analyses were analyzed with multivariable linear regression, adjusting for demographic, comorbidity, and voice use variables. Results Of the 101 patients enrolled, 75 completed the study. The mean (SD) age of the 75 completing participants was 55.7 (11.8) years and 53 (71%) were women. The participants who completed the study had mean (SD) voice-related work productivity impairment of 43% (27%) at baseline and 22% (23%) at 1 month after BoNT injection (difference, 20% [27%] improvement; 95% CI, 14%-27%; effect size, 0.74). Conclusions and relevance This case series study found that employed patients with spasmodic dysphonia reported voice-related work productivity impairment, which improved significantly 1 month after treatment with BoNT injection. The association of spasmodic dysphonia with voice-related work productivity appeared greater in women than men with comparable outcomes with BoNT treatment, but this exploratory sex-associated difference requires independent validation.

Background Eczema is a chronic inflammatory disease associated with impaired quality of life. We identified indoor environmental risk factors, to provide strong evidence for the prevention and control of eczema in preschool children. Methods Using a cross-sectional study with stratified random cluster sampling, we conducted a self-administered questionnaire survey among 8153 parents of children aged 2–8 years in 60 kindergartens in six districts of Urumqi city during August 2019. Results Among 8153 preschool children, 12.0% of the children have been diagnosed with eczema. Multivariate logistic regression analysis showed that caesarean section (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.03–1.36), being an only child (OR = 1.36, 95% CI: 1.18–1.57), presence of mould or moisture in the mother’s home before pregnancy (OR = 1.53, 95% CI: 1.17–2.00), presence of flies or mosquitoes in the dwelling currently (OR = 1.31, 95% CI: 1.10–1.55), pets kept in the child’s home currently (OR = 1.23, 95% CI: 1.01–1.51), presence of pets during child’s first year (OR = 1.45, 95% CI: 1.14–1.85), and family history of eczema (OR = 3.53, 95% CI: 2.98–4.19) are the risk factors for the development of eczema, whereas ethnicity other than the Han Chinese (OR = 0.77, 95% CI: 0.61–0.96) is a protective factor for eczema. Conclusion Preschool children in Urumqi are at a high risk of eczema, particularly those of the Han Chinese ethnicity. Parents should be attentive to the indoor living environment of children and take actions to reduce indoor humidity, pest control and elimination, and avoid raising pets to reduce the risk of development of eczema in children.

Objectives To explore the causes of cochlear implantation and reference function of old electrical stimulation electrode in cochlear reimplantation in children. Methods The causes, surgical methods and problems found during the operations of 24 cases of cochlear reimplantation in Henan Children's Hospital from June 2016 to April 2018 were analyzed. Results Twenty-three cases successfully completed the surgery of cochlear-reimplantation, and the remaining one case had approximately 1/3 of the anterior end of the residual cochlear electrode due to high resistance at the time of withdrawal of the electrodes. The causes of re-implantation were implant equipment failure (eleven cases), elevated impedance values of all electrodes after head trauma (two cases), and implant prolapse together with the electrode caused by a traffic accident (one case). Conclusion The old stimulus electrode can provide an important reference to reduce the risk of operation and ensure the success of the reoperation.

Background:The safe closure of atrial septal defect with deficient posterior-inferior or inferior vena cava rim is a controversial issue. Few studies have been conducted on the closure of atrial septal defect with deficient posterior-inferior or inferior vena cava rim without fluoroscopy. This study evaluated the feasibility and safety of echocardiography-guided transcatheter closure of atrial septal defect with deficient posterior-inferior or inferior vena cava rim.Methods:The data of 136 patients who underwent transcatheter atrial septal defect closure without fluoroscopy from March 2017 to March 2020 were retrospectively analysed. The patients were classified into the deficient (n = 45) and sufficient (n = 91) posterior-inferior or inferior vena cava rim groups. Procedure and the follow-up results were compared between the two groups.Results:Atrial septal defect indexed diameter and the device indexed diameter in the deficient rim group were both larger than that in the sufficient rim group (22.12 versus 17.38 mm/m2, p < 0.001; 24.77 versus 21.21 mm/m2, p = 0.003, respectively). There was no significant difference in the success rate of occlusion between two groups (97.78% in the deficient rim group versus 98.90% in the sufficient rim group, p = 1.000). During follow-up, the incidence of severe adverse cardiac events was not statistically significant (p = 0.551).Conclusions:Atrial septal defect with deficient posterior-inferior or inferior vena cava rim can safely undergo transcatheter closure under echocardiography alone if precisely evaluated with transesophageal or transthoracic echocardiography and the size of the occluder is appropriate. The mid-term results after closure are similar to that for an atrial septal defect with sufficient rim.

Background Although HIV is associated with increased risk of heart failure (HF), it is not known if people living with HIV develop HF at a younger age compared with individuals without HIV. Crude comparisons of age at diagnosis of HF between individuals with and without HIV does not account for differences in underlying age structures between the populations. Methods and Results We used Veterans Health Administration data to compare the age at HF diagnosis between veterans with and without HIV, with adjustment for difference in population age structure. Statistical weights, calculated for each 1‐year strata of veterans with HIV in each calendar year from 2000 to 2018, were applied to the veterans without HIV to standardize the age structure. We identified 5093 veterans with HIV (98% men, 34% White) with first HF episode recorded after HIV diagnosis (median age at incidence of HF, 58 years), and 1 425 987 veterans without HIV (98% men, 78% White) with HF (corresponding age, 72 years), with an absolute difference of 14 years. After accounting for difference in age structure, the adjusted median age at HF diagnosis for veterans without HIV was 63 years, 5 years difference with veterans with HIV ( P Conclusions Veterans with HIV are diagnosed with HF at a significantly younger age compared with veterans without HIV. These findings may have implications for HF prevention in individuals with HIV. Future studies are needed to make the findings more generalizable.

Background: Interpersonal violence is a significant public health issue. Routine health screening is a cost-effective strategy that may reduce harmful physical and mental consequences. However, existing research finds consistently low rates of violence screening offered by healthcare providers, e.g., nurses, nurse practitioners, physicians. There is a critical need for research that helps understand how providers' screening behaviors are impacted by individual-level and organizational-level factors to promote the uptake of routine screening for interpersonal violence. Two recent studies, i.e., The Health Care Providers study and Nurse Practitioners Violence Screening study, involved quantitative data collected to measure providers' screening behavior and multi-level factors impacting violence screening.Methods: The current analysis includes a combination of multi-center data collected from The Health Care Providers and Nurse Practitioners Violence Screening studies, respectively. The total sample is 389 providers across the United States. The proposed research develops a system-level multi-center structural equation model framework to rigorously integrate data from the two studies and examine providers' screening behavior for interpersonal violence based upon Theory of Planned Behavior from a quantitative perspective.Results & Conclusions: We successfully examine the efficacy of the Theory of Planned Behavior proposed by Ajzen to predict healthcare providers' screening behavior for interpersonal violence. Organizational factors, e.g., availability of policy for interpersonal violence screening, organizational priority given to violence screening relative to other priorities, and if providers within the health center are interested in improving care quality, were significantly associated with providers' screening behavior. The knowledge and insights generated from our study may facilitate the design and optimization of health professional training and practice environment, and lead to improved women's health and quality of care.

Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA-DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA-DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA-DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.

Objective: This study was designed to summarize the clinical characteristics, diagnosis and treatment of pharyngeal bronchogenic cysts in children to help in making the correct diagnosis and developing an appropriate treatment plan.Methods: The clinical data of 13 children with bronchogenic cysts in the pharynx, who were treated in otolaryngology head and neck surgery department between September 2013 and July 2019, were analyzed retrospectively. The clinical characteristics were evaluated, and the related factors for diagnosis and treatment were analyzed. Clinical characteristics and imaging features of three cases whose lesions located in the nasopharyngeal, oropharynx, and laryngopharyngeal were demonstrated.Results: All 13 children were male, the youngest being 4 days old, the oldest 6 years and 6 months, and the median age being 1 year and 4 months. Eight patients were diagnosed during a physical examination, and five patients visited the doctor with different degrees of upper airway obstruction. The mass was located in the nasopharynx in one patient, in the oropharynx in eight patients, and in the laryngopharynx in the other four patients. Computed tomography (CT) scanning, which is helpful for a topical diagnosis, showed a dense homogeneous mass. Electronic nasopharyngoscopy showed cystic masses of different sizes in the pharynx. All the children underwent cyst resection under general anesthesia, and the postoperative pathology result was a bronchogenic cyst. One child was lost to follow-up, but the remaining 12 children were followed up for between 6 months and 6 years, during which no recurrence of a cyst was found.Conclusion: Bronchogenic cysts are a rare cyst of the head and neck, and the most common site of the cyst is the oropharynx. The impact on airway obstruction depends on the location and size of the cyst. CT scanning is of great significance for diagnosis. Surgical treatment should be carried out as soon as possible after diagnosis, as surgery is the most effective way to treat bronchogenic cysts. Follow-ups should be carried out regularly to prevent cyst recurrence.

To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307–0.567)]. A longer duration of CM therapy (6–12 months, 12–18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I–IIIA (HR=0.50, 95% CI: 0.37–0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33–0.71), DFS was even longer among CM treatment group patients. Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398)

1. MicroRNAs are small noncoding RNA molecules that play crucial roles in gene expression. However, the comparative profiling of testicular and ovarian microRNAs in birds are rarely reported, particularly in pigeon.2. In this study, Illumina next-generation sequencing technology was used to sequence miRNA libraries of the gonads from six healthy adult utility pigeons. A total of 344 conserved known miRNAs and 32 novel putative miRNAs candidates were detected. Compared with those of ovaries, 130 differentially expressed (DE) miRNAs were identified in the testes. Among them, 70 miRNAs showed down-regulation in the ovaries, while another 60 miRNAs were up-regulated.3. Combining the results of the expression of target gene measurements and pathway enrichment analyses, it was revealed that some DEmiRNAs from the gonad samples involved in sexual differentiation and development (such as cli-miR-210-3p and cli-miR-214-3p) could down-regulate AR (androgen receptor). Cli-miR-181b-5p, cli-miR-9622-3p and cli-miR-145-5p were highly expressed in both the ovaries and testes, which could co-target HOXC9, and were related to regulation of primary metabolic processes. KEGG enrichment analysis showed that DEmiRNAs may play biological and sex-related roles in pigeon gonads.4. The expression profiles of testicular and ovarian miRNA in adult pigeon gonads are presented for the first time, and the findings may contribute to a better understanding of gonadal expression in poultry.

Shwachman-Diamond syndrome (SDS) is a rare and clinically heterogeneous bone marrow (BM) failure syndrome caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. Although SDS was described more than 50 years ago, its molecular pathogenesis is poorly understood due, in part, to the rarity and heterogeneity of the affected hematopoietic progenitors. To address this, we used single-cell RNA sequencing to profile scant hematopoietic stem and progenitor cells from patients with SDS. We generated a single-cell map of early lineage commitment and found that SDS hematopoiesis was left-shifted with selective loss of granulocyte-monocyte progenitors. Transcriptional targets of transforming growth factor beta (TGF-β) were dysregulated in SDS hematopoietic stem cells and multipotent progenitors, but not in lineage-committed progenitors. TGF-β inhibitors (AVID200 and SD208) increased hematopoietic colony formation of SDS patient BM. Finally, TGF-β3 and other TGF-β pathway members were elevated in SDS patient blood plasma. These data establish the TGF-β pathway as a candidate biomarker and therapeutic target in SDS and translate insights from single-cell biology into a potential therapy.

Objective: Syndrome differentiation is a unique part of traditional Chinese medicine (TCM). Syndrome factors play an important role in the diagnosis and treatment of TCM syndromes. Thromboelastography (TEG) intuitively reflects the blood status of patients with acute ischemic stroke (AIS) and is important in the treatment and prognosis of AIS. To identify the relationship between TCM syndrome factors and TEG in AIS patients and standardize TCM syndrome differentiation and treatment objectives, we designed a prospective cohort study of 103 AIS patients. Methods: We used the diagnostic criteria for AIS in the Chinese Guideline for Diagnosis and Management of Acute Ischemic Stroke 2010. Diagnosis of phlegm-heat and fu-organ excess syndrome was based on the TCM Scale for the Syndrome of Phlegm-heat and fu-organ Excess. The ischemic Stroke TCM Syndrome Factor Diagnostic Scale was used to identify and diagnose syndrome factors. General information, scores of syndrome factors and values of TEG parameters of all enrolled patients were recorded. Results: There were significant differences in internal fire and phlegm-dampness scores between patients with and without phlegm-heat and fu-organ excess syndrome (P .05) or between both syndrome factors and TEG parameters in patients without phlegm-heat and fu-organ excess syndrome. Conclusion: The syndrome factor internal fire is a potential predictor of increased platelet function and fibrinogen activity in AIS patients with phlegm-heat and fu-organ excess, and a potentially important predictor of blood hypercoagulability in TCM. Keywords: Clinical relevance, Phlegm-heat and fu-organ excess syndrome, Syndrome factors, Thromboelastography

PURPOSE The aim of this study was to determine participation rates and outcomes for patients with Takotsubo cardiomyopathy (TC) in a cardiac rehabilitation (CR) program. METHODS Patients at 2 academic medical centers with a discharge diagnosis of TC from January 2008 to March 2015 were retrospectively identified. Patients meeting the Mayo Clinic criteria for TC were cross-matched to the CR center affiliated with the hospitals to determine the referral rate and outcomes after completion of the program. RESULTS In total, 380 unique patients were identified who survived the index hospitalization. Eighteen patients (5%) were referred to CR, 15 enrolled, and of those enrolled, 10 patients (67%) completed the program. Patients undergoing percutaneous coronary intervention of a nonculprit vessel at the time of diagnosis was the only predictor for referral to CR (11% vs 1%, P = .01). The 10 patients who completed CR attended 33 ± 6 (range, 20-36) sessions. Weight and body mass index reduction were 2.8 ± 3.5 lb and 0.6 ± 0.7 kg/m (P = .04, both), respectively. Post-CR exercise duration was 37 ± 4 min/session, which improved by 13 ± 6 min/session from baseline (P < .01). Two patients entered the phase III maintenance program. One-year cardiac readmission rates were comparable among patients who completed CR and those who were referred but did not attend or complete CR (0% vs 13%, P = .47). CONCLUSIONS Referral for the TC population was low; however, enrollment and completion rates were adequate, with percutaneous coronary intervention in nonculprit vessel as the only predictor of CR referral. Limited data showed CR may help with weight reduction and improve exercise duration.

Polymorph-controlled crystallization of acetaminophen was conducted through femtosecond laser double-pulse irradiation. Dependence of the crystal form of acetaminophen on the pulse energy and doubl...

Background Distinct tube size is critical for the function of human tubular organs such as the lung, vascular system, and kidney. Aberrant tube sizes can lead to devastating human illnesses, including polycystic kidney disease. The Drosophila trachea provides a premier genetic system to investigate the fundamental mechanisms that regulate tube size. Results Here we describe the function of a novel gene, apnoia, in tube-size regulation. apn encodes an apical membrane protein, Apnoia (Apn), with three helical transmembrane domains. Loss-of-function apn mutants show shorter-tube and air-filling defects in larval trachea, whereas there are no obvious defects in embryonic trachea. Conversely, overexpression of apn in trachea leads to significant tube over-elongation. We analyzed apical luminal matrix and cell polarity in these longer tubes. It is interesting to note that we observed normal establishment of cell polarity, whereas all luminal matrix components are significantly reduced. In addition, we observed that some matrix components are localized in cytoplasmic vesicles, suggesting secretion defects in apn overexpressing trachea. Conclusion Taken together, these results strongly suggest the possibility that apn is directly or indirectly involved in vesicular trafficking to regulate tube size.

To evaluate the dynamic contrast-enhanced MRI parameters for monitoring the neoadjuvant chemotherapy (NAC) response in osteosarcoma prospectively. A total of 19 patients with osteosarcoma were recruited and underwent two dynamic contrast-enhanced MRI (DCE-MRI) examinations before and after chemotherapy. Patients with ≥ 90% tumor necrosis were defined as responders (10 patients), and those

Cephalosporin residues in the environment are a great concern, but bioremediation options do exist. Bacillus clausii T reached a removal rate of 100% within 8 h when challenged with a mixture of cefuroxime (CFX), cefotaxime (CTX), and cefpirome (CPR). The co-culture of B. clausii T and B. clausii O/C displayed a higher removal efficiency for the mixture of CFX, CTX and CPR than a pure culture of B. clausii O/C. B. clausii T alleviated the biotoxicity of CFX and CPR. What's more, the biotoxicity of for CFX and CPR transformation products released by the co-culture of B. clausii T and B. clausii O/C was lower than that in pure cultures. Real-time PCR was applied to detect the changes in the expression levels of the relevant antibiotic-resistance genes of B. clausii T during CFX and CPR degradation. The results indicated that CFX and CPR enhanced the expression of the β-lactamase gene bcl1. Hydrolysis, deacetylation and decarboxylation are likely the major mechanisms of CTX biodegradation by B. clausii. These results demonstrate that B. clausii T is a promising strain for the bioremediation of environmental contamination by CFX, CTX, and CPR.

Objective The purpose of this study was to find out the important lncRNA-miRNA-mRNA axis and pathway in osteosarcoma (OS) through bioinformatics analysis and verify the biological functions of lncRNA/miRNA/mRNA in OS through in vitro and in vivo assays. Methods The differential expression mRNAs and lncRNAs were identified through microarray analysis, and the altered pathways were identified by GSEA. The Pearson Coefficient was used to analyze the correlations between mRNAs and lncRNAs. Kaplan-Meier survival analysis was preformed using patient information in GEO database. Their target miRNAs were predicted by Targetscan and miRanda database and confirmed by dual luciferase reporter assay. QRT-PCR were utilized to detected the relative expressions of mRNAs, miRNAs and lncRNAs. The expressions of IL6R protein and pathway related proteins were detected by western blot. OS cell viability, migration and apoptosis were determined through MTT assay, Transwell assay and flow cytometry. Tumor formation in nude mice verified the influence of LINC01116 in vivo. Results The Jak-stat signaling pathway was activated in OS tissues. LINC01116 expression was positively correlated with IL6R expression. MiR-520a-3p targeted the 3’-UTR of LINC01116 and IL6R. Lower expression levels of miR-520a-3p significantly correlated with shorter survival of patients. LINC01116 and IL6R were up-regulated while miR-520a-3p was down-regulated in OS. LINC01116 and IL6R promoted the viability and migration of OS cells, while miR-520a-3p acted as a tumor suppressor. MiR-520a-3p inhibitor could rescue the suppressive effects of si-LINC011116 and si-IL6R on OS development. The Jak-stat signaling pathway related proteins were also down-regulated by miR-520a-3p. Down-regulation of LINC01116 inhibited the tumor growth in nude mice. Conclusion LINC01116 up-regulated IL6R in OS through targeting miR-520a-3p, thus activating the Jak-stat signaling pathway and promoting the progression of OS.

Key Points Question Is delirium associated with 30-day functional recovery in patients discharged to skilled nursing facilities after heart failure hospitalization? Findings In this cohort study of 20 495 patients from the US Department of Veterans Affairs health system discharged to skilled nursing facilities after heart failure hospitalization, delirium was associated with poor functional recovery. The baseline Activities of Daily Living score on admission to a skilled nursing facility was significantly worse among patients with delirium; patients with delirium also had significantly lower Activities of Daily Living improvement from baseline to follow-up assessments. Meaning Study results suggest that delirium on admission to skilled nursing facilities after heart failure hospitalization was associated with poor functional recovery., Importance A substantial number of patients discharged to skilled nursing facilities (SNFs) after heart failure (HF) hospitalization experience regression in function or do not improve. Delirium is one of few modifiable risk factors in this patient population. Therefore, understanding the role of delirium in functional recovery may be useful for improving outcomes. Objective To assess the association of delirium with 30-day functional improvement in patients discharged to SNFs after HF hospitalization. Design, Setting, and Participants This retrospective cohort study included patients hospitalized for HF in 129 US Department of Veterans Affairs hospitals who were discharged to SNFs from October 1, 2010, to September 30, 2015. Data were analyzed from June 14 to December 18, 2020. Exposures Delirium, as determined by the Minimum Data Set (MDS) 3.0 Confusion Assessment Method, with dementia as a covariate, determined via International Classification of Diseases, Ninth Revision (ICD-9) coding. Main Outcomes and Measures The difference between admission and 30-day MDS 3.0 Activities of Daily Living (ADL) scores. Results A total of 20 495 patients (mean [SD] age, 78 [10.3] years; 78.9% White; and 97% male) were included in the analysis. Of the total sample, 882 patients (4.3%) had delirium on an SNF admission. The mean (SD) baseline ADL score on admission to SNF was significantly worse among patients with delirium than without (18.3 [4.7] vs 16.1 [5.2]; P, This cohort study assesses the association between delirium and functional recovery for patients recently discharged to skilled nursing facilities after heart failure hospitalization.

Background Acupuncture plays a positive role in promoting the rehabilitation of post-stroke hemiplegia, but its specific central effect mechanism remains unclear. The changes of cerebral integrity, bilateral regulation and coordination are closer to the actual running state of brain after injury, while the research on bilateral cerebral reconstruction after unilateral motor pathway injury is not sufficient. The study of cerebral functional remodeling after stroke and mechanisms of acupuncture for post-stroke hemiplegia still faces many challenges. This study will explore the the underlying mechanisms of bilateral cerebral remodeling and acupuncture for post-stroke hemiplegia rehabilitation. Methods This is a single-center, cross-sectional, multimodal functional magnetic resonance imaging(fMRI) study, with participants and data analyst blinded. 24 post-stroke patients with motor dysfunction and 24 healthy subjects that meet the inclusion criteria will be recruited in this study. All the patients enrolled in this study will receive the conventional standard medical care according to their chief doctors. Clinical data including motor function scales, high-sensitivity C-reactive protein(hs-CRP), other related scales as well as fMRI imaging data will be collected at baseline and 2 weeks later. Functional connectivity(FC) is the primary and core outcome indicator of this study. Voxel-mirrored homotopic connectivity (VMHC), fractional anisotropy (FA),voxel-based morphometry (VBM), Fugl-Meyer Assessment(FMA) and hs-CRP are secondary outcome indicators. During the MRI scan, true or sham Yanglingquan(GB34) acupuncture stimulation on the left side and passive finger movement will be performed on the participants. The connection between cerebral imaging indicators and clinical indicators will be obtained by calculating the Pearson’s correlation coefficient. Discussion The results of our study will help to understand the cerebral remodeling mechanism of motor function improvement after stroke better and provide data support for the better application of acupuncture in clinical practice. Trial registration: Chinese Clinical Trial Registry (ChiCTR1900022220). Regisered on 30 March 2019. http://www.chictr.org.cn/showprojen.aspx?proj=37359

Retinoic acid receptor-related orphan nuclear receptor (ROR) γt is a member of the RORC nuclear hormone receptor family of transcription factors. RORγt functions as a critical regulator of thymopoiesis and immune responses. RORγt is expressed in multiple immune cell populations including Th17 cells, where its primary function is regulation of immune responses to bacteria and fungi through IL-17A production. However, excessive IL-17A production has been linked to numerous autoimmune diseases. Moreover, Th17 cells have been shown to elicit both pro- and anti-tumor effects. Thus, modulation of the RORγt/IL-17A axis may represent an attractive therapeutic target for the treatment of autoimmune disorders and some cancers. Herein we report the design, synthesis and characterization of three selective allosteric RORγt inhibitors in preclinical models of inflammation and tumor growth. We demonstrate that these compounds can inhibit Th17 differentiation and maintenance in vitro and Th17-dependent inflammation and associated gene expression in vivo, in a dose-dependent manner. Finally, RORγt inhibitors were assessed for efficacy against tumor formation. While, RORγt inhibitors were shown to inhibit tumor formation in pancreatic ductal adenocarcinoma (PDAC) organoids in vitro and modulate RORγt target genes in vivo, this activity was not sufficient to delay tumor volume in a KP/C human tumor mouse model of pancreatic cancer.

Objective: This study aimed to investigate the application of mini-incisions in complex preauricular fistula resection in children.Methods: A total of 78 children who were diagnosed with preauricular fistula infection between January 2017 and December 2019 were included in the study. Their clinical data were analyzed retrospectively, and surgical treatment with mini-incisions based on plastic surgery principles and techniques was provided.Results: All the patients achieved healing following the first application of the treatment. The patients were followed up for 6–42 months, and no recurrence or local auricular deformation occurred.Conclusion: The application of mini-incisions and plastic surgery techniques in complex preauricular fistula resection in children can achieve a good effect and improve the satisfaction of the children and their parents.

Background: As one of the important manifestations of neurogenic bowel dysfunction, constipation is characterized by high incidence and harmful effects. It has a negative impact on both physical and psychological health of patients. And there are no effective treatment options for this type of disease clinically. Therefore, this study is designed to examine the effect of the therapy of “combination 3 methods progression” in patients with neurogenic bowel dysfunction (constipated type). Methods: This is a randomized, controlled, parallel-design clinical trial. A total of 60 patients with neurogenic bowel dysfunction (constipated type) will be randomly assigned to intervention group and control group. The control group will receive 4 weeks of usual rehabilitation care, the intervention group will receive 4 weeks of the therapy of “combination 3 methods progression” in addition to usual rehabilitation care. The primary outcome is the number of spontaneous bowel movement per week. Secondary outcomes are stool characteristics, degree of difficulty in defecation, level of anxiety, level of depression, and level of self-efficacy. Discussion: The interventions of this protocol have been programmed to alleviate constipation in patients with neurogenic bowel dysfunction. Findings may provide preliminary evidence for clinical efficacy of the therapy of “combination 3 methods progression.” Trial registration: Chinese Clinical Trial Registry, IDF: ChiCTR2000041463. Registered on December 26, 2020.