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Blunt traumatic thoracic aortic injury (BTAI) is an extremely serious medical condition with a high rate of associated mortality. Recent advances in techniques such as thoracic endovascular repair offer new opportunities to manage the critical BTAI patients in an efficacious yet less invasive manner. A 65 year-old-male suffered from multiple injuries after a fall, including BTAI in the aortic arch, which resulted in dissection of the descending thoracic-abdominal aorta and iliac artery, development of an intimal flap in the left common carotid artery, and dissection of the left subclavian artery. Based on the imaging information of this patient and our clinical experience, the combined treatment of fenestrated thoracic endovascular repair and a chimney technique was immediately planned to fully repair these dissections and moreover prevent further dissection of the branching vessels, additionally to ensure sufficient blood flow in the left subclavian artery and left common carotid artery. The intervention yielded satisfactory early outcomes. Follow-up assessment at six months reported no symptoms or complications associated with the stent-graft. Computed tomography angiography further confirmed adequate stent-graft coverage of the aortic injury.

Three-dimensional speckle-tracking echocardiography (3D-STE) has been increasingly used to quantify right ventricular (RV) function. However, direct comparisons of 3D-STE with cardiac magnetic resonance (CMR) imaging for evaluation of RV function are limited. This study aimed to test the feasibility and accuracy of 3D-STE for the quantification of RV volumes, ejection fraction (EF), and longitudinal strain in comparison with CMR imaging and to determine whether 3D-STE for RV strain is superior to two-dimensional (2D) STE in comparison with CMR imaging.A total of 195 consecutive patients referred for both CMR imaging and echocardiography were studied. Right ventricular end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RVEF, and 3D RV longitudinal strain (3D-RVLS) of the free wall by 3D-STE and 2D-RVLS of the free wall by 2D-STE, were compared with CMR measurements. Pearson correlation and Bland-Altman analyses were used to assess the intertechnique agreement.Right ventricular 3D-STE was feasible in 174 patients (89%). Right ventricular volumes and EF determined by 3D-STE strongly correlated with CMR values (RVEDV, r = 0.94; RVESV, r = 0.96; RVEF, r = 0.91; all P .001). Three-dimensional STE slightly underestimated the RV volumes and longitudinal strain and overestimated the RVEF. The 3D-RVLS values correlated better than 2D-RVLS values with CMR values (0.85 vs 0.64, P .001) with smaller bias and narrower limits of agreement (bias: 2.0 and 2.6; limits of agreement: 8.5 and 12.5, respectively). The bias and limits of agreement for 3D-STE-obtained RVLS were increased in patients with RV dilation, RVEF45%, or lower frame rate compared with those with normal RV size, RVEF ≥ 45%, or higher frame rate, respectively. Right ventricular 3D-STE measurements were highly reproducible.The 3D-STE measurements of RV volumes, EF, and longitudinal strain are highly feasible and reproducible, and data measured by 3D-STE correlate strongly with those determined using CMR imaging. Thus, 3D-STE may be a valid alternative to CMR imaging for the quantification of RV function in everyday clinical practice.

In this work, we study the gate leakage mechanisms of E-mode ${p}$ - ${n}$ junction/AlGaN/GaN (PNJ) high electron mobility transistors (HEMTs), which have been shown to deliver low gate leakage and wide safe operating gate-bias range. The intrinsic gate leakage through the PNJ-gate was found to be limited by the transport of holes through the ${p}$ -GaN layer, which occurs via Poole-Frenkel emission and phonon-assisted tunneling in low and high gate bias region, respectively. In addition, lateral leakage current and the role of variable hopping process (VRH) are also discussed. Gate leakage current models based on the revealed mechanisms can quantitatively reproduce the gate-leakage behavior in the entire relevant range of gate biases and temperatures.

Intercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma, chronic obstructive pulmonary diseases and respiratory infections, and systemic diseases such as diabetes. Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit. The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration, but also enhance the clinical benefits to the patients with improved therapeutic outcomes. This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines. It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure, which is followed by recent advances in various strategies to overcome these barriers. Finally, the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized., Graphical abstract Strategies including molecular modification, polymeric conjugation, formulation technologies, etc. are being developed to extend pulmonary drug exposure. Inhaled medicines with extended lung exposure could be potentially favored for therapeutic efficacy.Image 1

Immune checkpoint inhibitors (ICIs) have achieved prominent efficacy in the treatment of numerous cancers, which is the most significant breakthrough in cancer therapy in recent years. However, ICIs are associated with a series of immune‐related adverse events (irAEs). Pneumonitis is an uncommon but potentially fatal irAE. In the case reported here, a patient with advanced small cell lung cancer (SCLC) had rapid progression of disease following chemotherapy and received ICIs. The patient experienced severe immune‐related hyperthermia followed by immune‐related pneumonitis. Fortunately, a good clinical response was achieved after the patient received corticosteroids and tocilizumab., The patient with SCLC reported here experienced severe immune‐related hyperthermia followed by immune‐related pneumonitis. Fortunately, a good clinical response was achieved after the patient received steroids and tocilizumab.

Objective Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been shown to be a safe and effective alternative therapy for ameliorating medically refractory primary Meige syndrome. However, the associations between DBS target position and surrounding electrophysiological properties as well as patients’ clinical outcomes remains largely unknown. In a large number of patients, we investigated electrophysiological features around stimulation targets and explored their roles in predicting clinical outcomes following bilateral GPi-DBS. Methods The locations of DBS active contacts along the long axis of the GPi in a standard space were calculated and compared among three groups with different clinical outcomes. The firing rates of individual neurons within the GPi were calculated for each patient and compared across the three groups. Results Compared with the bad group (poor clinical outcome), active contacts in the good group (good clinical outcome) and the best group (best clinical outcome) were located in the more posterior GPi. The average firing rates in the good and best groups were significantly higher than in the bad group, and this difference was pronounced within the ventral GPi. For the bad group, the average firing rates were significantly lower in the ventral than in the dorsal GPi. Conclusions This study suggests that DBS of the posterior GPi may produce better clinical outcomes during primary Meige syndrome treatment and that higher GPi neuronal activity, particularly within the ventral part, can be used as a biomarker to guide DBS electrode implantation during surgery.

Background Caloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms. Methods Sixty male Sprague–Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling. Results We found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion CR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.

Background To study the various factors affecting the anticoagulant effect of warfarin, and to promote the rational use of warfarin. Methods We collected the medical records of 125 hospitalized patients who used warfarin from January 2018 to December 2019. Statistical analysis was performed on characteristics such as gender, age, treatment, diabetes, hyperlipidemia, hyperthyroidism, hypothyroidism, hepatitis, renal insufficiency, and nephritis; along with other pathological factors, such as aspirin, clopidogrel, spironolactone, amiodarone, amlodipine, trimetazidine, bisoprolol, isosorbide, atorvastatin, furosemide, digoxin, metoprolol, acarbose, levamlodipine, enoxaparin, moxifloxacin, levofloxacin, other drug interactions, and comorbidities. Results Gender and age did not have a significant effect on the efficacy of warfarin. Infection and bleeding extended the number of days of warfarin administration. Acarbose, enoxaparin, and moxifloxacin had a likely effect on warfarin treatment-related indicators. Conclusions Warfarin anticoagulation is affected by many factors. Therefore, medical personnel should pay close attention to the impact of these factors on the anticoagulant effect of warfarin. This study found that warfarin-related bleeding adverse drug reactions and anticoagulant effects have a significant association. Bleeding not only affected the total number of days hospitalized, but also extended the number of days of warfarin administration. However, in terms of patients' pathological states, international normalized ratio values combined with drugs used were not associated with disease and may only be a reference for bleeding risk.

Li Zhang,1,2,* Minjie Liu,2,3,* Jianying Li,2,4,* Xiaoli Li,3,* Li Cheng,3 Yahong Ji,3 Na Li,3 Junning Wang2,3 1Department of Intensive Care Unit, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 2Xi’an Public Health Center, Xi’an, Shaanxi, 710200, People’s Republic of China; 3Department of Respiratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 4The Department of Respiratory Medicine, Xi’an Central Hospital, The Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, 710003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junning WangDepartment of Respiratory, Honghui Hospital, Xi’an Jiaotong University, No. 555, Youyi East Road, Nanshaomen, Xi’an, Shaanxi, 710054, People’s Republic of ChinaTel +86 02962818354Fax +86 02962818354Email wangjunningde@163.comBackground: Effective management of foreign-imported COVID-19 cases is a new and great challenge for China. Our study focused on the foreign-imported COVID-19 cases to provide detailed data for insights into the prevention, early diagnosis, treatment and control of imported COVID-19.Methods: For this observational and retrospective study, we investigated the clinical characteristics of imported COVID-19 cases that were confirmed by real-time RT-PCR in the Xi’an Public Health Center from 29 March 2020 to 31 August 2020.Results: Of the 79 patients with COVID-19, 19 (24.1%) had exposure to confirmed COVID-19 patients, 15 (19.0%) had exposure to suspicious COVID-19 patients, and 45 (56.9%) had an unclear history of exposure to confirmed patients. The mean age of the patients was 38 years, and 70 (88.7%) patients were male. Except for 2 severe cases, the remaining 58 (73.4%) cases displayed mild or moderate symptoms, and 19 (24.2%) infected patients were asymptomatic. Twenty-one (26.6%) patients were not diagnosed until a third or later nucleic acid test. Ten (12.7%) patients had chronic diseases. The most common manifestations of the patients were cough [18 (22.8%) cases], fever [9 (11.4%) cases] and sore throat [9 (11.4%) cases]. Forty-one (51.9%) cases showed abnormal chest CT images, To date, all patients have been discharged, and no patient has died.Conclusion: The imported COVID-19 cases in Xi’an were mainly young and middle-aged adults with mild or moderate symptoms who had a low rate of comorbidity, showed favourable laboratory and chest CT images, and had a better prognosis. Notably, for suspected COVID-19 cases, at least three consecutive nucleic acid tests should be carried out to avoid missed detection of infected patients. Except for severe cases, high-level medical resources are not necessary in most cases.Keywords: COVID-19, SARS-CoV-2, clinical characteristics, foreign-imported cases, pneumonia

By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.

Myocarditis (MC) is a common, potentially life-threatening inflammatory disease of the myocardium. A growing body of evidence has shown that mitogen-activated protein kinase 14 (MAPK14) participates in the pathogenesis of MC. However, the upstream regulators of MAPK14 remain enigmatic. Circular RNAs (circRNAs) have been identified to play vital roles in the pathophysiology of cardiovascular diseases. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in MC remain poorly understood. In this study, we determined a novel circRNA, circACSL1 (ID: hsa_circ_0071542), which was significantly upregulated in the acute phase of MC, and its dynamic change in expression was related to the progression of MC. We used lipopolysaccharide (LPS) to induce the inflammatory responses in the human cardiomyocytes (HCM) line for in vitro and in cellulo experiments . The pro-inflammatory factors (IL-1β, IL-6, and TNF-α), myocardial injury markers (cTnT, CKMB, and BNP), cell viability, and cell apoptosis were measured to evaluate the extent of myocardial inflammation and myocardial injury level. Functional experiments, including gain-of-function and loss-of-function, were then performed to investigate the pro-inflammatory roles of circACSL1. The results revealed that circACSL1 could aggravate inflammation, myocardial injury, and apoptosis in HCM. Mechanistically, circACSL1 acted as a sponge for miR-8055-binding sites to regulate the downstream target MAPK14 expression. Furthermore, overexpression of miR-8055 rescued the pro-inflammatory effects of circACSL1 on HCM, and the upregulation of MAPK14 induced by circACSL1 was attenuated by miR-8055 overexpression. Knockdown of circACSL1 or overexpression of miR-8055 reduced myocardial inflammation and myocardial injury level and these effects were rescued by overexpression of MAPK14. In summary, our study demonstrated that circACSL1 could aggravate myocardial inflammation and myocardial injury through competitive absorption of miR-8055, thereby upregulating MAPK14 expression. Moreover, circACSL1 may represent a potential novel biomarker for the precise diagnosis of MC and offer a promising therapeutic target for MC treatment.

The ever-increasing space exploration enterprise calls for novel and high-quality radiation-resistant materials, among which nonlinear optical materials and devices are particularly scarce. Two-dimensional (2D) materials have shown promising potential, but the radiation effects on their nonlinear optical properties remain largely elusive. We previously fabricated 2D bismuthene for mode-locking sub-ns laser; herein, their space adaption was evaluated under a simulated space radiation environment. The as-synthesized thin layers of bismuthene exhibited strong third-order nonlinear optical responses extending into the near-infrared region. Remarkably, when exposed to 60Co γ-rays and electron irradiation, the bismuthene showed only slight degradation in saturable absorption behaviors that were critical for mode-locking in space. Ultrafast spectroscopy was applied to address the radiation effects and damage mechanisms that are difficult to understand by routine techniques. This work offers a new bottom-up approach for preparing 2D bismuthene, and the elucidation of its fundamental excited-state dynamics after radiation also provides a guideline to optimize the material for eventual space applications.

Diurnal temperature range (DTR) is a meteorological indicator closely associated with global climate change. Thus, we aim to explore the effects of DTR on the outpatient and emergency room (O&ER) admissions for cardiovascular diseases (CVDs), and related predictive research. The O&ER admissions data for CVDs from three general hospitals in Jinchang of Gansu Province were collected from 2013 to 2016. A generalized additive model (GAM) with Poisson regression was employed to analyze the effect of DTR on the O&ER admissions for all cardiovascular diseases, hypertension, ischemic heart disease (IHD) and stoke. GAM was also used to preform predictive research of the effect of DTR on the O&ER admissions for CVDs. There were similar positive linear relationships between DTR and the O&ER visits with the four cardiovascular diseases. And the cumulative lag effects were higher than the single lag effects. A 1 °C increase in DTR corresponded to a 1.30% (0.99–1.62%) increase in O&ER admissions for all cardiovascular diseases. Males and elderly were more sensitivity to DTR. The estimates in non-heating season were higher than in heating season. The trial prediction accuracy rate of CVDs based on DTR was between 59.32 and 74.40%. DTR has significantly positive association with O&ER admissions for CVDs, which can be used as a prediction index of the admissions of O&ER with CVDs.

Human reliability analysis (HRA) for severe accidents is an important component of a Level 2 probabilistic risk assessment (PRA) for nuclear power plants. In this study, a Bayesian network (BN) is ...

Acute myeloid leukemia (AML) remains a devastating disease in need of new therapies to improve patient survival. Targeted adoptive T-cell therapies have achieved impressive clinical outcomes in some B-cell leukemias and lymphomas but not in AML. Double-negative T cells (DNTs) effectively kill blast cells from the majority of AML patients and are now being tested in clinical trials. However, AML blasts obtained from ∼30% of patients show resistance to DNT-mediated cytotoxicity; the markers or mechanisms underlying this resistance have not been elucidated. Here, we used a targeted clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) screen to identify genes that cause susceptibility of AML cells to DNT therapy. Inactivation of the Spt-Ada-Gcn5-acetyltransferase (SAGA) deubiquitinating complex components sensitized AML cells to DNT-mediated cytotoxicity. In contrast, CD64 inactivation resulted in resistance to DNT-mediated cytotoxicity. Importantly, the level of CD64 expression correlated strongly with the sensitivity of AML cells to DNT treatment. Furthermore, the ectopic expression of CD64 overcame AML resistance to DNTs in vitro and in vivo. Altogether, our data demonstrate the utility of CRISPR/Cas9 screens to uncover mechanisms underlying the sensitivity to DNT therapy and suggest CD64 as a predictive marker for response in AML patients.

The aim of this study was to investigate the prognostic significance of BRAFV600E in cell-free (cf) DNA (cfBRAFV600E) and lesion tissues (ltBRAFV600E) in pediatric Langerhans cell histiocytosis (LCH). This study included a total of 140 patients with successfully detected cfBRAFV600E and ltBRAFV600E at diagnosis. Treatment response at week 6 was correlated with both cfBRAFV600E and ltBRAFV600E. Moreover, the patients with positive cfBRAFV600E had a much lower 3-year progression-free survival (PFS) rate and a higher progression/reactivation rate than those with negative cfBRAFV600E (47.1% ± 7.6% vs. 78.4% ± 5.1%, P < 0.0001; 44.6% vs. 19.0%, P = 0.001, respectively). However, no significant difference was found in the 3-year PFS rate or progression/reactivation rate between patients with positive and negative ltBRAFV600E (P = 0.348 and 0.596, respectively). In addition, after patients were divided into group A (both cfBRAFV600E and ltBRAFV600E positive, n = 56), group B (ltBRAFV600E positive and cfBRAFV600E negative, n = 28), and group C (both cfBRAFV600E and ltBRAFV600E negative, n = 56), there was a significant difference in the 3-year PFS rate and progression/reactivation rate among the three groups (47.1% ± 7.6%, 92.9% ± 6.1%, and 72.2% ± 6.1%, P < 0.001; 44.6%, 3.6%, and 26.8%, P < 0.001, respectively). In the multivariate analysis, cfBRAFV600E and age at diagnosis remained independent prognostic factors for 3-year PFS in childhood LCH. Therefore, cfBRAFV600E was more closely associated with important clinical characteristics, treatment response at week 6, and prognosis than ltBRAFV600E.

Background: Kidney injury is a well-described adverse event of tyrosine kinase inhibitors (TKIs), thought to be mediated predominantly through glomerular damage. However, risk factors for kidney injury and the mechanism of injury are poorly defined in a wide range of cancers. Methods: This is a secondary analysis of 539 patients in the control arm of an international randomized clinical trial of patients with hepatocellular carcinoma treated with sorafenib, a vascular endothelial growth-factor receptor (VEGFR) TKI. Risk factors for developing acute kidney injury (AKI) while being treated with sorafenib were evaluated by multivariable logistic regression. We performed subgroup analyses of AKI stratified into proteinuric and non-proteinuric AKI. Results: While on study, 16% of patients developed an AKI. A decrease in systolic blood pressure was positively associated with developing any AKI (OR 1.70, 95% CI 1.03–2.82). In the subgroup analyses, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI (OR 2.15, 95% CI 1.00–4.61), but there was no association with developing a non-proteinuric AKI. Conclusions: In patients with hepatocellular carcinoma taking sorafenib, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI. However, there was no association between a decrease in blood pressure and the development of a non-proteinuric AKI. Thus, the development of AKI among patients taking VEGFR-TKIs cannot be fully explained by a hemodynamic effect. Our study highlights the need to better understand the varying mechanisms of kidney injury in patients.

Abstract Cardiovascular disease (CVD) has long been the leading cause of death worldwide, and myocardial infarction (MI) accounts for the greatest proportion of CVD. Recent research has revealed that inflammation plays a major role in the pathogenesis of CVD and other manifestations of atherosclerosis. Overwhelming evidence supports the view that macrophages, as the basic cell component of the innate immune system, play a pivotal role in atherosclerosis initiation and progression. Limited but indispensable resident macrophages have been detected in the healthy heart; however, the number of cardiac macrophages significantly increases during cardiac injury. In the early period of initial cardiac damage (e.g., MI), numerous classically activated macrophages (M1) originating from the bone marrow and spleen are rapidly recruited to damaged sites, where they are responsible for cardiac remodeling. After the inflammatory stage, the macrophages shift toward an alternatively activated phenotype (M2) that promotes cardiac repair. In addition, extensive studies have shown the therapeutic potential of macrophages as targets, especially for emerging nanoparticle-mediated drug delivery systems. In the present review, we focused on the role of macrophages in the development and progression of MI, factors regulating macrophage activation and function, and the therapeutic potential of macrophages in MI.

Photonic topological valley kink states have become a significant research frontier with a plethora of applications. Unlike the guided modes with adjustable widths in conventional waveguides, the v...

The intraoperative ischemia in partial nephrectomy (PN) often leads to postoperative renal function impairment and fibrosis, which can be regulated by macrophage polarization. We have previously demonstrated that microvesicles derived from human Wharton’s Jelly mesenchymal stromal cells (hWJMSC-MVs) attenuated renal ischemia-induced renal fibrosis and contained a substantial quantity of hepatocyte growth factor (HGF). Herein, we investigated whether MSC-MVs regulate macrophage polarization and ameliorate renal fibrosis following ischemia-PN via transferring HGF. A rat model of ischemia-PN was established by 45 min of left renal ischemia followed by removal of 1/3 upper left kidney. MSC-MVs were injected through the tail vein immediately after ischemia. Renal injury biomarkers were measured and histologic analysis was performed to analyze renal injury. A co-culture model of THP-1 macrophages and MSC-MVs was utilized. The expression of M1 markers and M2 markers were determined to evaluate macrophage polarization. MSC-MV administration significantly ameliorated renal inflammation, lesions, and fibrosis in ischemia-PN rats, and promoted M2 macrophage polarization both in rat remnant renal tissues and LPS-treated THP-1 cells. These effects of MSC-MVs were compromised when HGF expression was downregulated in MSC-MVs. Collectively, MSC-MVs promote M2 macrophage polarization and attenuate renal fibrosis following ischemia-PN via transferring HGF.

BACKGROUND To explore the vitamin D status with its demographic and lifestyle factors including dietary, supplementation, and physical activity in 0-5 years old children. METHODS This was a large population-based cross-sectional multicentre study in which the children were recruited from 12 Children's Health Care Centers by a stratified cluster random-sampling method in 10 cities in Jiangsu Province, China. RESULTS A total number of 5289 children were investigated. The prevalence of vitamin D deficiency was 30.1%. The concentration of 25 hydroxyvitamin D was 64.0 (46.3-83.0) nmol mL-1 after adjustment for covariates. Children with higher risk of vitamin D deficiency were more likely to be at older age, girls, survey conducted in spring, location in southern Jiangsu province, residence in urban, outdoor activity 400 IU day-1 (all p 150.0 g day-1 , milk consumption

Food and energy security are important issues that threaten human survival and development. The rice–wheat rotation system provides a stable source of food for more than 20% of the world's population, but there have been no reports on the energy balance of different rice–wheat rotation systems. This study evaluates the energy inputs and outputs of three rice–wheat rotation systems and their energy production efficiency through the study of dry direct‐seeded, wet direct‐seeded, and transplanted rice–wheat rotation systems. The results of the study showed that the average total energy inputs in the dry direct‐seeded, wet direct‐seeded, and transplanted rice–wheat rotation systems were 58,677, 74,083, and 69,022 MJ ha−1, respectively. The production resources with more energy input in rice–wheat rotation system were all related to water and fertilizer. The energy input in the rice season accounts for more than 50.69% of the total energy input in the rice–wheat rotation system. At the same time, rice–wheat rotation production is highly dependent on nonrenewable energy. Among the three rice–wheat rotation systems, the transplanted rice–wheat rotation system had the highest total energy output and net energy, while the dry direct‐seeded rice–wheat rotation had the highest energy use efficiency, energy productivity, energy profitability, and human energy profitability. The results showed that the key to reducing the energy input in the rice–wheat rotation system is to reduce the amount of water and fertilizer. The transplanted rice–wheat rotation system is more suitable for promotion in rice–wheat rotation production areas with good irrigation conditions, while the dry direct‐seeded rice–wheat rotation system is highly compatible with the current development direction of low energy consumption and high energy efficiency in agricultural production and is suitable for promotion in rice–wheat production areas with poor irrigation conditions.

Background and Purpose. Patients with early-stage Parkinson’s disease (PD) have gait impairments, and gait parameters may act as diagnostic biomarkers. We aimed to (1) comprehensively quantify gait impairments in early-stage PD and (2) evaluate the diagnostic value of gait parameters for early-stage PD. Methods. 32 patients with early-stage PD and 30 healthy control subjects (HC) were enrolled. All participants completed the instrumented stand and walk test, and gait data was collected using wearable sensors. Results. We observed increased variability of stride length (SL) ( P < 0.001 ), stance phase time (StPT) ( P = 0.004 ), and swing phase time (SwPT) ( P = 0.011 ) in PD. There were decreased heel strike (HS) ( P = 0.001 ), range of motion of knee ( P = 0.036 ), and hip joints ( P < 0.001 ) in PD. In symmetry analysis, no difference was found in any of the assessed gait parameters between HC and PD. Only total steps ( AUC = 0.763 , P < 0.001 ), SL ( AUC = 0.701 , P = 0.007 ), SL variability ( AUC = 0.769 , P < 0.001 ), StPT variability ( AUC = 0.712 , P = 0.004 ), and SwPT variability ( AUC = 0.688 , P = 0.011 ) had potential diagnostic value. When these five gait parameters were combined, the predictive power was found to increase, with the highest AUC of 0.802 ( P < 0.001 ). Conclusions. Patients with early-stage PD presented increased variability but still symmetrical gait pattern. Some specific gait parameters can be applied to diagnose early-stage PD which may increase diagnosis accuracy. Our findings are helpful to improve patient’s quality of life.

BackgroundProgressive cavitating leukoencephalopathy (PCL) is thought to result from mutations in nuclear genes affecting mitochondrial function and energy metabolism. To date, mutations in two subunits of complex I, NDUFS1 and NDUFV1, have been reported to be related to PCL.MethodsPatients underwent clinical examinations, brain MRI, skin biopsy and muscle biopsy. Whole-genome or whole-exome sequencing was performed on the index patients from two unrelated families with PCL. The effects of the mutations were examined through complementation of the NDUFV2 mutation by cDNA expression.ResultsThe common clinical features of the patients in this study were recurring episodes of acute or subacute developmental regression that appeared in the first years of life, followed by gradual remissions and prolonged periods of stability. MRI showed leukoencephalopathy with multiple cavities. Three novel NDUFV2 missense mutations were identified in these families. Complex I deficiency was confirmed in affected individuals’ fibroblasts and a muscle biopsy. Functional and structural analyses revealed that these mutations affect the structural stability and function of the NDUFV2 protein, indicating that defective NDUFV2 function is responsible for the phenotypes in these individuals.ConclusionsHere, we report the clinical presentations, neuroimaging and molecular and functional analyses of novel mutations in NDUFV2 in two sibling pairs of two Chinese families presenting with PCL. We hereby expand the knowledge on the clinical phenotypes associated with mutations in NDUFV2 and the genotypes causative for PCL.

This study aimed to investigate the mental health status of nurses from low‐risk areas of novel coronavirus (COVID‐19) pandemic, its potential impact factors, and the main stressors under the normalized prevention and control in China. A mobile phone app‐based survey was conducted among registered nurses in Jiangsu province via a region‐stratified sampling method. The questionnaire consisted of items on the demographic characteristics of the nursing staff and their Depression, Anxiety, Stress Scale‐21 (DASS‐21) along with questions for self‐assessment of stressors that are associated with COVID‐19. STROBE guideline was used. Among 1803 nurses who were working in the low‐risk areas in Jiangsu, 22.0%, 29.8%, and 16.1% of them reported moderate to extreme levels of depression, anxiety, and stress, respectively. Having 11–15 years of working experience and being a fixed‐term contract nurse were associated with experiencing worse mental health outcomes while supporting‐Wuhan working experience and having mental health preparation course training were independent factors that had beneficial impact on their psychological well‐being afterward. In terms of source of pressure, a key finding of this study is that the main stressor among these nurses was the lack of patient’s understanding and cooperation (71.2%) which calls for better psychosocial communication between nurses and patients. The present findings would provide information for other regions at low risk of COVID‐19 and may aid the provision of support and interventions for the benefit of the psychological well‐being of nurses who are exposed to life‐threatening occupational risks and are more vulnerable to the pandemic than others.

Demand responsive transit (DRT) services in suburban regions serve residents as the complements of the public transportation. Since suburban DRT service usually faces demand fluctuation in some special situations, such as terrible weather, DRT operators have recourse to temporal rental vehicles to satisfy all requests. There are two types of rental contracts. In the first case, the costs of rental vehicles are similar to the costs of owned vehicles, and the multi-trip vehicle routing problem is studied. In the second case, the costs of outbound trips are not covered by DRT companies, and the open vehicle routes are introduced. In this paper, a mixed integer linear programming formulation is proposed to model the route optimization problem of the suburban DRT service, in which the number of rental vehicles and two classes of routes should be decided simultaneously. To solve the proposed model, a branch-and-price algorithm is designed, which has two pricing subproblems to generate two classes of routes, respectively. From the results of experiments, it can be found that the service sequence is introduced, when open routes are involved. Renting vehicles can help DRT companies save operational costs even in daily operations.

We report a processing technique to form a surface reinforcement layer (SRL) in GaN metal-insulator-semiconductor high-electron mobility transistors (MIS-HEMTs) with the aim to suppress device dynamic on-resistance (RON) degradation caused by long-term hot-electron stress. The SRL is a crystalline (Al)GaON layer formed by reconstruction of the heterojunction surface through plasma oxidation and high temperature annealing. MIS-HEMTs with SRL exhibit substantially suppressed dynamic RON degradation than the conventional devices without SRL, after long-term hot-electron stress. The (Al)GaON SRL exhibits substantially enhanced thermal stability and strong immunity to energetic carriers. The SRL-enabled suppression of hot-electron-induced degradation is further verified by the electroluminescence characterizations.

Objective Current National Comprehensive Cancer Network guidelines for gastroenteropancreatic neuroendocrine tumors (GEPNETs) recommend complete (R0) surgical resection of the primary tumor and metastases, if feasible. However, large multicenter studies of recurrence patterns of GEPNETs after resection have not been performed. Methods Patients 18 years or older who presented to 7 participating National Comprehensive Cancer Network institutions between 2004 and 2008 with a new diagnosis of a small bowel, pancreas, or colon/rectum neuroendocrine tumor (NET) and underwent R0 resection of the primary tumor, and synchronous metastases, if present, were included in this analysis. Descriptive statistics and Kaplan-Meier estimates were used to calculate recurrence rates and time-associated end points, respectively. Results Of 294 patients with GEPNETs, 50% were male, 88% were White, and 99% had Eastern Cooperative Oncology Group performance status 0 to 1. The median age was 55 years (range, 20-90). The median follow-up time from R0 resection was 62.1 months. Recurrence rates were 18% in small bowel NETs (n = 110), 26% in pancreatic NETs (n = 141), and 10% in colon/rectum NETs (n = 50). The frequency of surveillance imaging was highly variable. Conclusions R0 resection was associated with variable risk of recurrence across subtypes. Further research to inform refinement of guidelines for the appropriate duration of surveillance after R0 resection is needed.

Serious performance decline arose for perovskite light-emitting diodes (PeLEDs) once the active area was enlarged. Here we investigate the failure mechanism of the widespread active film fabrication method; and ascribe severe phase-segregation to be the reason. We thereby introduce L-Norvaline to construct a COO−-coordinated intermediate phase with low formation enthalpy. The new intermediate phase changes the crystallization pathway, thereby suppressing the phase-segregation. Accordingly, high-quality large-area quasi-2D films with desirable properties are obtained. Based on this, we further rationally adjusted films’ recombination kinetics. We reported a series of highly-efficient green quasi-2D PeLEDs with active areas of 9.0 cm2. The peak EQE of 16.4% is achieved in = 3, represent the most efficient large-area PeLEDs yet. Meanwhile, high brightness device with luminance up to 9.1 × 104 cd m−2 has achieved in = 10 film., Performance of perovskite LED tends to decline as the active area increases, thus understanding the failure mechanism is paramount to surmount this limitation. Here, the authors report severe phase-segregation to be the cause, and introduce L-Norvaline to overcome it, as the result, highly-efficient 9.0 cm2 green PeLED is realised.

In this letter, a dielectric resonator antenna (DRA) with an engraved groove and a comb-like metal wall for beamwidth enhancement in both E- and H-planes is proposed. First, with an engraved groove, the radiation intensity on the top wall of the rectangular DRA can be enhanced, which significantly broadens the half-power beamwidth (HPBW) in the E-plane. Second, by placing a regular notched metal wall around the grooved DRA, HPBWs in both E- and H-planes can be greatly widened simultaneously. Finally, for the further improvement of HPBW in the H-plane, the regular notched wall is replaced by a 3-D printed comb-like metal wall. Vertical currents can be induced on the comb-like wall due to the coupling of the DRA, which can increase gain at low elevation angles and further enhance HPBW of 20°. Thus, HPBWs of the proposed antenna in both cutting planes can be improved step by step without scarifying each other and bandwidth. To verify the proposed design, an antenna prototype is fabricated and measured, which shows an impedance bandwidth of 38.2% (2.58–3.8 GHz), with excellent HPBW performance of 248° and 148° in the E- and H-planes, respectively.

Objective The aim of the present study was to summarize the clinical characteristics, treatment strategies, and clinical results for anterior tibial plateau fractures caused by hyperextension injuries. Methods We performed a retrospective analysis of 26 cases of anterior tibial plateau fractures that were treated with open reduction and internal fixation from January 2016 to December 2019, including 16 men and 10 women, aged 26–68 years old, with an average age of 47 ± 12.5 years. According to the three‐column theory classification, there were 16 cases of single‐column fractures (9 cases of anteromedial fractures and 7 cases of anterolateral fractures), 3 cases of two‐column fractures (anteromedial + anterolateral fractures), and 7 cases of three‐column fractures. Options for the surgical approach included anteromedial, anterolateral, modified anterior median, and anterolateral + posteromedial incision. The implants included a T‐shaped plate, an L‐shaped plate, a horizontal plate, and a TomoFix plate. The surgical approach and fixation method were selected based on the characteristics of the anterior tibial fracture. The Rasmussen radiological criteria were used to evaluate the effects of fracture reduction and fixation. The knee joint function was evaluated using the knee function evaluation criteria of the Hospital for Special Surgery. Medial and lateral stress tests, the Lachman test, and the pivot shift test were used to evaluate the stability of the knee joint. The range of knee motion was recorded. Results All cases were followed up for 12–24 months, with an average follow up of 15.7 months. The operation time was (148 ± 42) min; the intraoperative blood loss was (150 ± 50) mL. A total of 22 cases were anatomically reduced and 4 cases were well‐reduced, and the compression reduction rate was 100%. According to the Rasmussen radiology scoring, 17 cases were excellent and 9 cases were good. The excellent and good rate was 100%. The fracture healing time was 3.3 months. There is no difference in fracture healing time for different fracture types. Both the Lachman and pivot shift test findings were normal in 24 patients and nearly normal in 2 patients. The posterior drawer test was normal in 25 patients and close to normal in 1 patient. The varus stress test was normal in 24 patients and nearly normal in 2 patients, while the valgus stress test was normal in 23 patients, nearly normal in 2 patients, and abnormal in 1 patient. The range of motion (ROM) was 100°–137°, with an average of 125° ± 11.7°. The Hospital for Special Surgery (HSS) knee score at the last follow up was 79–98 points, with an average of 87.54 ± 8.36 points; the results were excellent in 21 cases and good in 5 cases. Therefore, 100% of results were excellent or good. Two cases had superficial wound infections after the operation. The recovery of 2 patients with common peroneal nerve injury was poor. Conclusion The appropriate surgical approach and fixation method were performed according to the different positions of the anterior tibial fracture and satisfactory results were obtained after surgery., (A1) Anteromedial tibial plateau fracture. (A2) The anterior medial approach and T‐shaped locking plate fixation were used. (B1) Anterolateral tibial plateau fracture. (B2) Anterolateral incision was used and the simple anterior compression of the tibia was fixed with the horizontal plate. If combined with a split fracture, an L‐shaped plate was used. (C1) Anteromedial + anterolateral fractures. (C2) The modified anterior median approach was used. The fixation was used with the horizontal plate. (D1) Tibial plateau hyperextension three‐column fractures. (D2) Both anterolateral and posteromedial approaches were used. The fixation included a T‐shaped plate and an L‐shaped plate.

Aim To develop a model for predicting renal recovery in cardiac surgery patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT). Methods Data from a prospective randomized controlled trial, conducted in a tertiary hospital to compare the survival effect of two dosages of hemofiltration for continuous RRT in cardiac surgery patients between March 20, 2012 and August 9, 2015, were used to develop the model. The outcome was renal recovery defined as alive and dialysis-free 90 days after RRT initiation. Multivariate logistic regression with a stepwise backward selection of variables based on Akaike Information Criterion was applied to develop the model, which was internally validated using bootstrapping. Model discrimination, calibration, and clinical value were assessed using the concordance index (C-Index), calibration plots, and decision curve analysis, respectively. Results Totally, 211 patients with AKI requiring RRT (66.8% male) with median age of 57 years were included. The incidence of renal recovery was 33.2% (n = 70). The model included six variables: body mass index stratification, baseline estimated glomerular filtration rate, hypertension, sepsis, mean arterial pressure, and mechanical ventilation. The C-Index for this model was 0.807 (95%CI, 0.744-0.870). After correction by the bootstrap, the C-Index was 0.780 (95%CI, 0.720-0.845). The calibration plots indicated good consistency between actual observations and model prediction of renal recovery. Decision curve analysis demonstrated the model was clinical usefulness. Conclusion We developed and validated a model to predict the chance of renal recovery in cardiac surgery patients with AKI requiring RRT. This article is protected by copyright. All rights reserved.

BACKGROUND: The SARS-CoV-2 pneumonia infection is associated with high rates of hospitalization and mortality and this has placed healthcare systems under strain. Our study provides a novel method for the progress prediction, clinical treatment and prognosis of NCP, and has important clinical value for timely treatment of severe NCP patients. OBJECTIVE: To summarize the clinical features and severe illness risk factors of the patients with novel coronavirus pneumonia (NCP), in order to provide support for the progression prediction, clinical treatment and prognosis of NCP patients. MATERIALS AND METHODS: A total of 196 NCP patients treated in our hospital from January 25, 2020 to June 21, 2020 were divided into the severe group and the mild group. The clinical features of the two groups were analyzed and compared. The risk factors were explored by using multivariate logistic regression, and the receiver operating characteristic (ROC) curve was obtained. The correlations of the risk factors with the prognosis of NCP were investigated combined with the lung function test. RESULTS: The primary clinical symptoms of 196 cases of NCP included fever in 167 cases (85.2%) and cough in 121 cases (61.73%). The chest computed tomography (CT) scans of the 178 cases (90.81%) showed a typical ground-glass opacification. In 149 cases, the lymphocyte count was decreased, while the levels of creatine kinase (CK), lactate dehydrogenase (LDH), c-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and D-dimer (D-D) increased. 44 cases (22.45%) were found to be severely ill. The multivariate logistic regression analysis demonstrated that age, underlying disease, length of hospital stay, body mass index (BMI), LDH, chest CT visual score, absolute lymphocyte count (ALC) and CRP were risk factors for severe

Human sapovirus (SaV) is an important causative agent of nonbacterial gastroenteritis in humans. However, little is known about its circulation in China. To study the prevalence and diversity of human SaV genotypes circulating in eastern China, a 3-year environmental surveillance combined with next generation sequencing (NGS) technology was conducted. A total of 36 raw sewage samples were collected from January 2017 to December 2019 in Jinan and processed. Thirty-five (97.22%) samples were positive for human SaV genome in quantitative RT-PCR assay; 33 (91.67%) samples were positive in nested RT-PCR assay on partial capsid VP1 sequence and all amplicons were further analyzed separately by NGS. Among those, ten genotypes belonging to the genogroups of GI, GII, GIV, and GV were identified by NGS, including 4 major genotypes (GI.2, GI.1, GV.1 and GI.3) and 6 uncommon genotypes (GII.5, GII.1, GII.NA1, GII.3, GI.6 and GIV.1). A temporal switch of predominant genotype was observed from GI.2 to GI.1 around June 2019. Local and foreign sequences clustered together in some branches according to phylogenetic analysis, indicating frequent transmission of various lineages in different regions of the world. Environmental surveillance provides a comprehensive picture of human SaV in China. NGS-based environmental surveillance improves our knowledge on human SaV circulating in communities greatly and should be encouraged as a sensitive surveillance tool. Supplementary Information The online version contains supplementary material available at 10.1007/s12560-021-09469-x.

The quality and safety of the aquatic products have gradually become the focus of global attention. In this study, the environmental eukaryotic and fungi communities in pond-cultured grass carp (Ctenopharyngodon idellus) and the koi carp (Cyprinus carpio L.) were investigated. For comparative analysis, the alpha diversity shows that the environmental microbial abundance in the koi carp groups were higher than that in the grass carp groups, while beta diversity reveals that the differences of the microbial community composition and structures in the grass carp groups were significantly higher than those in the koi carp groups. Meanwhile, the environmental microbial diversity of grass carp groups was higher than that of koi carp groups at phylum level, but showed no significant difference at genus level. Additionally, the dominant total phyla were Opisthokonta, Stramenopiles plusAlveolates plusRhizaria, Archaeplastida, Cryptophyceae, and Centrohelida for the 18S rRNA gene and Ciliophora, Chlorophyta, and Ascomycota for the ITS2 rRNA gene in both of the two carp groups. Additionally, annotation analysis showed that the biomarkers in the grass carp groups are significantly higher than those of the koi carp groups. Furthermore, the functional prediction of Funguild showed significant difference in outputs, while similarity in trophic modes and guild types between the two carp groups. Meanwhile, the total relative abundances of animal pathogen, fungal parasite, and plant pathogen were extremely similar between the two carp groups. Surprisingly, one pathogenic fungus of genus Fusarium was identified in both the environments of two carp groups based on filtered operational taxonomic unit tables. Overall, this is the first robust report to understand the characteristics of environmental eukaryotic microorganisms and fungi in the edible and ornamental carps. Our results also provide the basic data for the prevention of fungal diseases and the healthy culture of the carps.

Objective To establish trimester-specific reference intervals (TSRIs) for blood lipid profiles in Chinese women and explore their associations with pregnancy outcomes. Methods Participants were women with singleton pregnancies aged 18-45 years without pre-existing chronic diseases who delivered from January 2018 to December 2018 from an ongoing cohort in Beijing, China. Baseline information and pregnancy outcomes were from the medical records. Blood lipid levels were measured at 7-13, 24-28, and 32-34 weeks of pregnancy. We estimated TSRIs for lipid profiles using an indirect Hoffmann method and evaluated their associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, macrosomia, low birth weight, large or small for gestational age, and preterm delivery. Results The established TSRIs were 3.21-5.38, 4.64-7.56, and 4.86-8.20 mmol/L for total cholesterol; 0.37-1.81, 1.14-3.49, and 1.61-4.63 mmol/L for triglycerides; 1.12-2.19, 1.33-2.49, and 1.24 2.31 mmol/L for high-density lipoprotein cholesterol; 1.33-2.98,1.97-4.36, and 2.02-4.92 mmol/L for low-density lipoprotein cholesterol from first trimeseter to third trimester, respectively. Both higher and lower levels of lipid profiles than TSRIs were associated with adverse pregnancy outcomes. Conclusion We suggested TSRIs for blood lipid levels in a Chinese population. Inappropriate lipid levels were associated with adverse pregnancy outcomes.

BACKGROUND Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum. Patients with protein C (PC) and protein S (PS) deficiency are prone to thrombosis. In contrast, patients with primary hyperfibrino-lysis tend to bleed. CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with "tuberculous pleurisy" and treated with anti-tuberculosis drugs and prednisone. The coagulation-related laboratory results showed decreased fibrinogen, PC activity, PS activity, and antithrombin Ш activity. The immune-related laboratory results showed positive antinuclear antibody, anti-Smith antibody, anticardiolipin antibody (ACL), anti-β2-glycoprotein I antibody (aβ2GPI) and direct Coomb’s test and decreased complement 3 and complement 4. Thoracoscopy was performed and bloody pleural fluid was drained. Pathology of the pleural biopsy showed lymphocytes, plasma cells, and a few eosinophils in adipose and fibrous connective tissue. Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases. The patient was finally diagnosed with SLE and primary hyperfibrinolysis, and was treated with prednisolone, hydroxychloroquine, and compound cyclophosphamide. CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI. SLE and primary hyperfibrinolysis can coexist in one patient, with both a risk of thrombosis and a risk of bleeding.

The patient was male, 57 years old, who was treated for "upper abdominal pain and discomfort for 4 hours". The pain was severe, with back radiation, without cold fever, nausea, vomiting, chest tightness, shortness of breath, skin or yellow eyes, also without hematemesis or black stool. Physical examination: without yellow skin and sclera, with right upper abdomen tenderness and positive Murphy sign. There were no other obvious positive signs. Abdominal CT：cholecystitis with possible occupancy, and multiple common bile duct stones. Laboratory tests: White blood cells was 10.88×109/ L, neutrophilic granulocyte was 84%, Glutamic transaminase was 666 IU/L. Past medical history: hypertension and diabetes. Preliminary diagnosis: Acute cholecystitis, Common bile duct stones, Abnormal liver function, High blood pressure, Diabetes, Admitted to hospital. Handling measures: fasting, pain relief, anti-infection, liver protection, fluid replacement treatment, and monitor blood sugar, blood pressure, and further improve the inspection.

Objective: The primary purpose of this study was to explore the safety of peripheral intravenous catheter (PIVC) replacement every 96 h compared to that of clinically indicated catheter removal. Methods: A prospective, single-blind, randomized controlled trial was conducted. A random number table method was used. Six hundred patients treated with PIVC intravenous infusion in 10 nursing units of a hospital from September to October 2019 were selected. Sixty were collected from each nursing unit, including 30 in the clinically indicated replacement group and 30 in the routine replacement group. The incidence of phlebitis, catheter-related infection (CRI), occlusion, infiltration, and any form of infusion therapy failure were compared between the two groups. SPSS 23.0 software was used. Results: The dwelling times of PIVC in the clinically indicated replacement group and routine replacement group were significantly different (hours) (83.62 ± 50.08, 69.75 ± 25.54, t = 3.021, p = 0.003). The incidence of any form of infusion therapy failure (RR = 4.448, 95% CI: 3.158–6.265, p Conclusion: Replacement of PIVC every 96 h is safer than clinically indicated.

Background DNA damage repair mutations (DDRm) are common in patients with metastatic castration-resistant prostate cancer (mCRPC). The optimal standard therapy for this population is not well described. Methods A multi-institutional, retrospective study of patients with mCRPC and DDRm was conducted. Patient data, including systemic therapies and responses, were collected. The decline in prostate-specific antigen ≥ 50% from baseline (PSA50) and overall survival (OS) from the treatment start were compared by mutation and treatment type. A multivariable Cox proportional hazards model for OS was created that controlled for DDRm, first-line treatment received for mCRPC, and clinical factors. Results The most common DDRm observed among 149 men with mCRPC were BRCA1/2 (44%), CDK12 (32%), and ATM (15%). The majority received first-line abiraterone (40%) or enzalutamide (30%). The PSA50 rate with first-line abiraterone was lower for CDK12 (52%) than BRCA1/2 (89%; P = .02). After first-line abiraterone or enzalutamide, the median OS was longest with second-line carboplatin-chemotherapy (38 months) in comparison with abiraterone or enzalutamide (33 months), docetaxel (17 months), or cabazitaxel (11 months; P = .02). PSA50 responses to carboplatin-based chemotherapy were higher for BRCA1/2 (79%) than ATM (14%; P = .02) or CDK12 (38%; P = .08). In a multivariable analysis, neither the specific DDRm type nor the first-line treatment was associated with improved OS. Conclusions Responses to standard therapies were generally superior in patients with BRCA1/2 mutations and inferior in patients with ATM or CDK12 mutations. The DDRm type did not independently predict OS. After progression on first-line abiraterone or enzalutamide, carboplatin-based chemotherapy was associated with the longest OS. These findings may inform treatment discussions and clinical trial design and require prospective validation.

Background. Osteoporosis is characterized by low bone mass, deterioration of bone tissue structure, and susceptibility to fracture. New and more suitable therapeutic targets need to be discovered. Methods. We collected osteoporosis-related datasets (GSE56815, GSE99624, and GSE63446). The methylation markers were obtained by differential analysis. Degree, DMNC, MCC, and MNC plug-ins were used to screen the important methylation markers in PPI network, then enrichment analysis was performed. ROC curve was used to evaluate the diagnostic effect of osteoporosis. In addition, we evaluated the difference in immune cell infiltration between osteoporotic patients and control by ssGSEA. Finally, differential miRNAs in osteoporosis were used to predict the regulators of key methylation markers. Results. A total of 2351 differentially expressed genes and 5246 differentially methylated positions were obtained between osteoporotic patients and controls. We identified 19 methylation markers by PPI network. They were mainly involved in biological functions and signaling pathways such as apoptosis and immune inflammation. HIST1H3G, MAP3K5, NOP2, OXA1L, and ZFPM2 with higher AUC values were considered key methylation markers. There were significant differences in immune cell infiltration between osteoporotic patients and controls, especially dendritic cells and natural killer cells. The correlation between MAP3K5 and immune cells was high, and its differential expression was also validated by other two datasets. In addition, NOP2 was predicted to be regulated by differentially expressed hsa-miR-3130-5p. Conclusion. Our efforts aim to provide new methylation markers as therapeutic targets for osteoporosis to better treat osteoporosis in the future.

Cereal β-glucan is a type of valuable dietary fiber that mainly exists in the aleurone, subaleurone, and endosperm of some cereal grains. β-Glucan is acknowledged as a functional food ingredient owing to its multiple health benefits, including the prevention of diabetes, reduction in the incidence of cardiovascular disease, antitumor effects, antioxidant activities, and immunostimulation. It is well documented that cellulose synthase-like CslF/H/J genes encode synthases responsible for β-glucan biosynthesis in cereal grains. Recently, β-glucan has been widely applied as an emulsion stabilizer, thickening agent, fat substitute, and bioactive ingredient in the food industry due to its water solubility, viscosity, gelation property, and health benefits. Therefore, the present paper aims to review the molecular characteristics, synthase gene family, and food application of cereal β-glucan in recent years.

Studies on the association of microalbuminuria with adverse outcomes in patients with hypertension remain controversial. This meta-analysis aimed to assess the predictive value of microalbuminuria in hypertensive patients. PubMed and Embase databases were comprehensively searched for studies that published from their inceptions to July 10, 2020. Observational studies reporting the association of microalbuminuria (defined as urinary albumin excretion 30 and 300 mg/24 h urine or albumin/creatinine ratio 30–300 mg/g from a spot urine or equivalent value) with all-cause mortality or major adverse cardiovascular events (MACEs) in hypertensive patients were selected. Nine studies with a total of 19,893 hypertensive patients were included. When compared with those without microalbuminuria, hypertensive patients with microalbuminuria had an increased risk of all-cause mortality (risk ratio [RR] 1.68; 95% confidence interval [CI] 1.46–1.93) and MACEs (RR 1.40; 95% CI 1.22–1.62), respectively. Gender-specific analysis indicated that microalbuminuria was significantly associated with an increased risk of all-cause mortality (RR 1.61; 95% CI 1.17–2.21) in men but not in women (RR 1.18; 95% CI 0.78–1.80). This meta-analysis suggests that microalbuminuria is independently associated with higher risk of MACEs and all-cause mortality in hypertensive patients. Determination of microalbuminuria has potential to improve the risk classification of hypertension.

As a two-dimensional semiconductor with many physical properties, including, notably, layer-controlled electronic bandgap and coupled spin-valley degree of freedom, monolayer MoSe2 is a strong candidate material for next-generation opto- and valley-electronic devices. However, due to substrate effects such as lattice mismatch and dielectric screening, preserving the monolayer's intrinsic properties remains challenging. This issue is generally significant for metallic substrates whose active surfaces are commonly utilized to achieve direct chemical or physical vapor growth of the monolayer films. Here, we demonstrate high-temperature-annealed Au foil with well-defined (100) facets as a weakly interacting substrate for atmospheric pressure chemical vapor deposition of highly crystalline monolayer MoSe2. Low-temperature scanning tunneling microscopy/spectroscopy measurements reveal a honeycomb structure of MoSe2 with a quasi-particle bandgap of 1.96 eV, a value comparable with other weakly interacting systems such as MoSe2/graphite. Density functional theory calculations indicate that the Au(100) surface exhibits the preferred energetics to electronically decouple from MoSe2, compared with the (110) and (111) crystal planes. This weak coupling is critical for the easy transfer of monolayers to another host substrate. Our study demonstrates a practical means to produce high-quality monolayers of transition-metal dichalcogenides, viable for both fundamental and application studies.

Background Disrupted placental functioning due to stress can have lifelong implications. Cumulative stress and trauma are likely to have lasting impacts on maternal physiological functioning and offspring development, resulting in increased risk for later-life complex disorders for which racial disparities exist. Methods This study examined the association between maternal lifetime stress and placental mitochondrial DNA mutational load in an urban multiethnic cohort. Maternal lifetime exposure to stressful events was assessed using the validated Life Stressor Checklist–Revised. Whole mitochondrial DNA sequencing was performed and mutations were determined for 365 placenta samples with complete exposure and covariate data. Multivariable regression was used to model maternal lifetime stress in relation to placental mitochondrial DNA mutational load. Racial/ethnic differences were examined by cross-product terms and contrast statements. Gene-wise analyses were conducted. Results We identified 13,189 heteroplasmies (Phred score > 10,000, minor allele frequency 1). Women experiencing increased psychosocial stress over their lifetime exhibited a higher number of total placental mitochondrial mutations (β = .23, 95% confidence interval = .03 to .42) and heteroplasmic mutations (β = .18, 95% confidence interval = .05 to .31) but not homoplasmic mutations (β = −.008, 95% confidence interval = −.03 to .01); the strongest associations were observed among Black women and genes coding for NADH dehydrogenase and cytochrome c oxidase subunits. Conclusions Cumulative maternal lifetime stress is associated with a greater mitochondrial mutational load, particularly among Black women. The impact of racial/ethnic differences in mutational load on placental function directly affecting offspring development and/or leading to chronic disease disparities warrants further investigation.

Taking the mobile edge computing paradigm as an effective supplement to the vehicular networks can enable vehicles to obtain network resources and computing capability nearby, and meet the current large-scale increase in vehicular service requirements. However, the congestion of wireless networks and insufficient computing resources of edge servers caused by the strong mobility of vehicles and the offloading of a large number of tasks make it difficult to provide users with good quality of service. In existing work, the influence of network access point selection on task execution latency was often not considered. In this paper, a pre-allocation algorithm for vehicle tasks is proposed to solve the problem of service interruption caused by vehicle movement and the limited edge coverage. Then, a system model is utilized to comprehensively consider the vehicle movement characteristics, access point resource utilization, and edge server workloads, so as to characterize the overall latency of vehicle task offloading execution. Furthermore, an adaptive task offloading strategy for automatic and efficient network selection, task offloading decisions in vehicular edge computing is implemented. Experimental results show that the proposed method significantly improves the overall task execution performance and reduces the time overhead of task offloading.

Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities is an extremely rare autosomal recessive mitochondrial disease caused by biallelic mutations in MECR. Using whole-exome sequencing, we identified a novel homozygous MECR mutation (c.910G > T, p.Asp304Tyr) in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy. With lipoic acid treatment, the disease progression was under control, and neither visual impairment nor optic atrophy was observed. To our knowledge, this is the first study about MECR-related mitochondrial disease in a Chinese patient and the first to report that supplementation with lipoic acid is a possible effective therapeutic strategy for this disease.

The clinical trial of vaccine efficacy is designed to compare the difference of incidence rate of disease or infections between vaccine group and placebo group, and to calculate the vaccine protection rate. Up to now, 22 COVID-19 vaccine candidates were under evaluation in phase III clinical trials, with the first two mRNA vaccines Moderna, and Pfizer/BioNTech announced efficacy of 94.1% and 95.0% for symptomatic COVID-19. However, several doubts concerning these results were raised, particularly by Peter Doshi, who speculated that a real efficacy of Pfizer/BioNTech’s mRNA vaccine could be as low as 29%. The debates around the efficacy of the COVID-19 vaccines became hot than ever in China, which might lead to increased vaccine skepticism, vaccination hesitation and undermine public confidence. Therefore, we need to have a better understanding on the efficacy data and interpret the results correctly. The selection of appropriate clinical endpoints with specific definition is critical. Hierarchical endpoints are often used in vaccine clinical trials to comprehensively evaluate the protective efficacy. Definition of hierarchical endpoints on basis of WHO clinical progression scale for COVID-19 could help to evaluate vaccine efficacy against COVID-19 with different severity, and compare the data from different trials. In general, vaccine efficacy is expected to be higher for the clinical endpoints with higher severity. In addition, both sensitivity and specificity of the disease surveillance system could have impacts on the vaccine efficacy. Specificity is more important than sensitivity, especially in the case of low incidence rate of the endpoint, which has a great impact on the protective efficacy of the vaccine, and often leads to the underestimation of vaccine efficacy. We compared phase III efficacy trial protocols of COVID-19 vaccine candidates sponsored by Moderna, Pfizer/BioNTech, AstraZeneca/University of Oxford and Johnson & Johnson, according to these impact factors mentioned above. Comparing with Moderna, AstraZeneca/University of Oxford and Johnson & Johnson’s trials to adopt a sensitive definition of suspected COVID-19 cases, Pfizer/BioNTech’s surveillance for diseases was mostly based on a passive surveillance involving self-report and self-sampling for case screening, which could compromise the sensitivity of the surveillance system capturing suspected COVID-19 cases. In addition, diagnostic testing to confirm the causative pathogen is important. However, the sensitivity of quantitative RT-PCR, the current goldstandard assay for diagnosis of SARS-CoV-2, is imperfect and influenced by viral load, sample type, and timing. Thus, collecting more than one specimen from suspected cases at more than one time points during the disease course, could results in a better sensitivity as well as specificity. Importantly, the serologic tests of antibody targeting at the N protein of SARS-CoV-2 could be used to identify whether it is naturally infected by SARS-CoV-2. At last, sharing and opening of trial protocols and the disclosure of trial data will contribute to better and more scientific evaluation of the efficacy of COVID-19 vaccine candidates. Extending the period of case surveillance and accumulating data on the protective efficacy of COVID-19 vaccines can contribute to understand the true protective efficacy of the vaccine.