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Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by progressive cognitive decline. Early diagnosis and dynamic monitoring are essential to the treatment and care of AD but challenging. Here we develop a noninvasive, blood-based AD detection method based on surface plasmonic resonance imaging (SPRi) technique. The functionalized sensing SPRi chips were constructed with self-assembled loop-displaying peptoid nanosheets to improve the detection sensitivity of plasma amyloid β42 (Aβ42). We analyze the plasma from 30 clinically diagnosed AD patients, 29 amnestic cognitive impairment (aMCI) patients, and 30 control individuals and demonstrate that this sensing system can significantly distinguish the three groups with high sensitivity and specificity. In the follow-up studies of the aMCI patients, we find that decrease in the binding signals in the patients correlates with the disease progression into AD whereas the almost unchanged signals correlate with stable disease remaining at aMCI status. These results show the capability of the peptoid-nanosheet-based SRPi sensing system for the early diagnosis and dynamic monitoring of AD.

Objective Cardiovascular disease (CVD) is the leading cause of death for American women, yet young women are rarely the target population of CVD prevention campaigns. This study investigated young women’s exposure to CVD information. Methods We surveyed 331 females ages 15–24 years to determine 1) whether participants felt informed about heart disease or stroke, 2) their exposure to heart disease information sources over the past year, and 3) whether they had ever discussed CVD-related topics with healthcare providers. Results Over half of participants reported feeling not informed about heart disease (52%) or stroke (59%). Participants were more likely to report feeling informed if they were exposed to information from websites or social media, or if they had ever discussed family history of heart disease, personal risk for heart disease, or high blood pressure with their healthcare provider. Conclusions Most young women did not feel informed about CVD. Exposure to specific information sources and discussions with healthcare providers may help improve this. Practice implications Public health campaigns should promote cardiovascular health through websites and social media popular amongst young women. Healthcare providers should discuss CVD risk factor modification with young patients in order to promote cardiovascular health across the life course.

Background and Purpose: Quantitative electroencephalogram (QEEG) parameters have been previously utilized in prognosis following acute ischemic stroke (AIS). However, the use and interpretation of QEEG parameters remain scarce following endovascular treatment (EVT) of AIS.Methods: AIS patients were prospectively enrolled following EVT, and 24-hour EEG monitoring was conducted. Global delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DTABR), and relative band power were analyzed. Primary outcome was a poor outcome (modified Rankin Scale ≥4 at 90-day follow-up). Multivariate logistic regression and diagnostic analyses were performed.Results: Poor outcome was seen in 35.5% (11/31) of enrolled patients. Multivariable logistic regression identified that higher DAR (OR 1.10, 95% CI 1.02-1.18, p = 0.02) and higher DTABR (OR 1.13, 95% CI 1.01-1.27, p = 0.02) were associated with poor outcome. DAR ≥14.3 demonstrated high sensitivity (90.9%), specificity (90.0%) and accuracy (90.3%) for poor outcome.Conclusions: Early evidence of elevated DAR and DTABR on quantitative EEG was associated with poor outcome at 90 days following EVT for AIS.

Targeted observation is an appealing procedure for improving model predictions. However, studies on oceanic targeted observations have been largely based on modeling efforts, and there is a need for field validating operations. Here, we report the results of a field targeted observation that is designed based on the sensitive areas identified by the Conditional Nonlinear Optimal Perturbation approach to improve the 7th day thermal structure prediction in the Yellow Sea. By introducing the technique of cycle data assimilation and the new concept of time-varying sensitive areas, an observing strategy is designed and validated by a set of Observing System Simulation Experiments. Then, the impact of targeted observations was investigated by a choreographed field campaign in the summer of 2019. The results of the in-field Observing System Experiments show that, compared to conventional local data assimilation, conducting targeted observations in the sensitive areas can yield more benefit at the verification time. Furthermore, dynamic analysis demonstrates that the refinement of vertical thermal structures is mainly caused by the changes in the upstream horizontal temperature advection driven by the Yellow Sea Cold Water Mass circulation. This study highlights the effectiveness of targeted observations on reducing the forecast uncertainty in the ocean.

Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting dopamine receptors, Dopamine receptor agonists are a class of drugs similar in function and structure to dopamine and can directly act on dopamine receptors and activate it. Clinically, Dopamine receptor agonist drugs have achieved significant therapeutic effects on prolactinoma and Parkinson's Disease. In the study, we virtually screened a series of potential effective agonists of Dopamine receptor by computer techniques. Firstly, we used the Molecular Docking (LibDock) step to screen out some molecules that can dock well with the protein. Then, analysis of toxicity prediction and ADME (adsorption, distribution, metabolism and excretion) were carried out. More precise molecular docking (CDOCKER) and 3-Dimensional Quantitative Structure-Activity Relationship Modeling Study(3D-QSAR) pharmacophore generation were implemented to research and explore these compounds' binding mechanism with Dopamine receptor. Last but not least, to assess compound's binding stabilities, we carried out a molecular dynamic analysis. As the results show, two compounds (ZINC000008860530 and ZINC000004096987) from the small molecule database (ZINC database) were potential effective agonists of Dopamine receptor. These two compounds can combine with Dopamine receptor with higher affinity and proved to be no toxic. The cell experiment showed that two compounds could inhibit the proliferation and PRL secretion of MMQ cells (pituitary tumor cells). Thus, this study provided valuable information about Dopamine receptor agonist-based drug discovery. So, this study will benefit patients with prolactinoma and Parkinson’s disease a lot.

To identify novel prognostic and therapeutic targets for osteosarcoma patients, we compared the gene expression profiles of osteosarcoma and control tissues from the GSE42352 dataset in the Gene Expression Omnibus. Differentially expressed genes were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment and protein-protein interaction network analyses. Survival curve analyses indicated that osteosarcoma patients with lower mRNA levels of cyclin-dependent kinase 1 (CDK1) and topoisomerase II alpha had better prognoses. Various computer-aided techniques were used to identify potential CDK1 inhibitors for osteosarcoma patients, and PHA-793887 was predicted to be a safe drug with a high binding affinity for CDK1. In vitro, MTT and colony formation assays demonstrated that PHA-793887 reduced the viability and clonogenicity of osteosarcoma cells, while a scratch assay suggested that PHA-793887 impaired the migration of these cells. Flow cytometry experiments revealed that PHA-793887 dose-dependently induced apoptosis in osteosarcoma cells. Western blotting and enzyme-linked immunosorbent assays indicated that CDK1 expression in osteosarcoma cells declined with increasing PHA-793887 concentrations. These results suggest that PHA-793887 could be a promising new treatment for osteosarcoma.

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.

Chronic low back pain (CLBP), lasting >3 months, is the end result of multiple pathogenic factors. Unfortunately, little is known about CLBP pathogenesis, which limits its advancements in clinical therapy and disease management. This paper summarizes the known pathological axes of CLBP, involving both peripheral and central systems. In particular, this paper details injurious nerve stimulation, inflammation-induced peripheral pathway, and central sensitization. Lumbar components, such as intervertebral disc (IVD), facet joints, muscles, fascia, ligaments, and joint capsules, contain pain receptors called nociceptors. Degeneration of the aforementioned lumbar components activates inflammatory pathways, which can directly damage nerves, lower nociceptor threshold to fire action potentials (AP), and cause pain. Additionally, damaged lumbar IVDs and endplates can also lead to the pathologic invasion of nerve growth and innervation, followed by the compression of herniated IVDs on nerve roots, thereby causing traumatic neuropathic pain. The central mechanism of CLBP involves alteration of the sensory processing of the brain and malfunction of the descending pain modulatory system, which facilitates pain amplification in the center nervous system (CNS). Lastly, abnormalities in the brain biochemical metabolism, activation of glial cells, and subsequent inflammation also play important roles in CLBP development. Taken together, inflammation plays an important role in both peripheral and central sensitization of CLBP. Due to the heterogeneity of CLBP, its pathological mechanism remains complex and difficult to understand. Therefore, it is a worthy field for future research into the subcomponents of CLBP pathogenesis, in order to distinguish the specific form of the disease, identify its origins, and develop corresponding highly effective comprehensive therapy against CLBP.

The aim of the study is to interpret the effects of air-impingement jet drying (AIJD) on drying kinetics, color, polyphenols, and antioxidation ability of Boletus aereus slices. Page model was most suitable for expressing and predicting AIJD curves of B. aereus slices. The moisture-effective diffusion coefficient of AIJD ranged from 7.8876 × 10-10 to 2.1426 × 10-9 m2 /s, and AIJD also showed high efficiency due to its low activation energy (45.37 kJ/mol). AIJD is better for B. aereus slices than hot air drying (HAD) in accelerating the drying rate (DR) and shortening drying time, and maintaining color. p-hydroxybenzoic acid, protocatechuic acid, and rutin were identified in B. aereus slices by ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS). Total polyphenols, flavanone, phenolic acids, and antioxidant activities were significantly lower in dried B. aereus slices than those in fresh B. aereus slices. In AIJD, drying temperature had the greatest effect on the quality of B. aereus slices, and AIJD at 50 °C is the optimum drying condition for B. aereus slices. PRACTICAL APPLICATION: Boletus aereus occurs in many countries all over the world. In this paper, the effect of AIJD on color, polyphenols, and antioxidation ability in B. aereus slices and its drying kinetics were studied. AIJD is an efficient drying method for B. aereus by decreasing its drying time, increasing DR, and protecting the color of B. aereus. These findings have provided important reference basis for people to have a better understanding of AIJD method, which was used to dry B. aereus. This study also provides a new technique for drying B. aereus, which could improve dry efficiency and reduce drying cost.

Background and purposeCurrent randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs.MethodsA comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality.ResultsThe meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death.ConclusionsHaemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.

A novel delivery system for cisplatin was constructed based on electrostatics-mediated assemblies of gold nanoclusters and PEGylated cationic peptide (cisplatin@GC-pKs). Encapsulated cisplatin in the as-formed micelle like assemblies was observed to demonstrate improved cellar uptake and enhanced chemotherapeutic efficiency in the cisplatin-resistant lung cancer cells. In vivo assays further confirmed that cisplatin@GC-pKs had profound anti-tumor efficiency due to deep penetration and accumulation of nanoscale cisplatin@GC-pKs via the enhanced permeability and retention (EPR) effect at tumor tissues. The constructed cisplatin@GC-pKs in this work demonstrated enhanced anti-tumor activity for lung cancer therapy, as well as a potential treatment strategy for a variety of cisplatin-resistance related malignancies.

During the COVID-19 epidemic, the treatment of critically ill patients has been increasingly difficult and challenging. During the epidemic, some patients with neurological diseases also have COVID-19, which could be misdiagnosed and cause silent transmission and nosocomial infection. Such risk is high in a neurological intensive care unit (NCU). Therefore, prevention and control of epidemic in critically ill patients is of utmost importance. The principle of NCU care should include comprehensive screening and risk assessment, weighing risk against benefits and reducing the risk of COVID-19 transmission while treating patients as promptly as possible.

AimStroke is the leading cause of disability and death in China. Ischaemic stroke accounts for about 60%–80% of all strokes. It is of considerable significance to carry out multidimensional management of ischaemic cerebrovascular diseases. This evidence-based guideline aims to provide the latest detailed and comprehensive recommendations on the diagnosis, treatment and secondary prevention of ischaemic cerebrovascular diseases.MethodsWe had performed comprehensive searches of MEDLINE (via PubMed) (before 30 June 2019), and integrated the relevant information into charts and distributed to the writing group. Writing group members discussed and determined the recommendations through teleconference. We used the level of evidence grading algorithm of Chinese Stroke Association to grade each recommendation. The draft was reviewed by the Guideline Writing Committee of Chinese Stroke Association Stroke and finalised. This guideline is fully updated every 3 years.ResultsThis evidence-based guideline is based on the treatment, care and prevention of ischaemic cerebrovascular diseases, which emphasises on pathogenesis evaluation, intravenous thrombolysis, endovascular therapy, antiplatelet therapy, prevention and treatment of complications, and risk factor management.ConclusionsThis updated guideline presents a framework for the management of ischaemic cerebrovascular diseases. Timely first-aid measures, professional care in the acute stage, and proactive secondary prevention will be helpful to patients.

Retinol-binding protein-4 (RBP-4) along with the lipid profile plays crucial roles in Acute coronary syndrome (ACS). The study aimed to investigate the correlation of RBP-4, lipoprotein combine index (LCI), and RBP-4 + LCI with ACS. 163 ACS and 77 non-CAD in patients were consecutively enrolled in this study. The serum level of RBP-4 was measured via enzyme-linked immunosorbent assay. LCI was calculated using the formula: total cholesterol × triglyceride × low-density lipoprotein cholesterol/high-density lipoprotein cholesterol. RBP-4 ≥4 ng/ml, LCI ≥16 and LCI ≥16 + RBP-4 ≥4 ng/ml were new independent risk factors of ACS, and OR value of LCI ≥16 + RBP-4 ≥4 ng/ml was higher than that of RBP-4 and LCI combined (all p p p p

Background: Lymphocyte-to-monocyte ratio (LMR) is involved in all stages of coronary atherosclerosis and related to coronary artery disease (CAD). However, the correlation between LMR and the coronary plaque burden of CAD is not clearly elucidated. Therefore, this study aimed to investigate their correlation in patients with CAD. Methods: A total of 1953 consecutive eligible inpatients with suspected CAD were retrospectively included in this study. They were assigned into CAD (n = 564) and non-CAD groups (n = 1389). All patients underwent coronary computed tomographic angiography to evaluate coronary stenosis and coronary artery calcification (CAC). Spearman’s tests were used to analyze the correlation between CAC score and LMR. Multivariate logistic regression models were set up to assess the risk factors of CAD. Results: Patients with CAD had lower LMR value than patients without CAD (P = 0.001). LMR was negatively correlated with CAC score and was an independent risk factor of CAC score (P < 0.05). Multivariate logistic regression model showed that LMR ≤4.8 was a newly independent risk factor of CAD (all P < 0.05). Additionally, the new risk score model was compared with the Framingham model and showed that NRI was 4.9%, which proved that the new risk score model improved the prediction capability of CAD. Conclusion: LMR ≤4.8 is a new independent risk factor of CAD. LMR value was negatively correlated with CAC score and could be used as a new marker to evaluate the coronary plaque burden of CAD.

Supplemental Digital Content is available in the text., Background The aim of this study was to evaluate the diagnostic and risk predictive value of emerging proinflammatory and anti-inflammatory adipocytokines on coronary artery disease (CAD). Patients and methods The study involved 259 inpatients suspected acute coronary syndrome who underwent coronary angiography. Demographic, clinical characteristics, and coronary artery stenosis rated by Gensini score were collected by cardiovascular doctors. The levels of serum inflammatory adipocytokines were evaluated by ELISA. The correlations of the cytokines with clinical parameters were assessed. Receiver operating characteristic curves were constructed for the diagnosis of CAD. Results The 259 inpatients were assigned to the CAD (n = 180) and control groups (n = 79). Compared with the control group, the CAD group displayed significantly higher serum levels of retinol-binding protein-4 (RBP4), pentraxin 3 (PTX3), galectin-3 (GAL-3), and plasminogen activator inhibitor (PAI-1), and significantly lower levels of netrin-1 (NTN1), interleukin-37 (IL-37), and adiponectin (ADP) (all P < 0.05). PAI-1 was significantly upregulated, and IL-37 and ADP were significantly downregulated in the three-vessels CAD subgroup compared to the one- and two-vessels CAD subgroups (P < 0.05). The RBP4, PTX3, GAL-3, PAI-1, and IL-37 inflammatory cytokines were significantly positively correlated with Gensini score, and ADP was negatively correlated (all P < 0.001). IL-37 was a more accurate anti-inflammatory biomarker than NTN1 and ADP. Combining cytokines significantly increased the sensitivity and specificity. Conclusion The inflammatory adipocytokines GAL-3, RBP4, PTX3, NTN1, and IL-37 were more effective than the classical biomarkers PAI-1 and ADP in the diagnosis and risk assessment of CAD patients.

Bile duct injury is a common complication of hepatobiliary surgeries in clinical practice with poorly satisfactory treatment outcomes. Implanting a tissue-engineered tubular scaffold for supporting and replacing defected native bile duct is an important treatment option for bile duct injury. Here a dual-layer tubular scaffold with poly (lactic-co-glycolic acid) (PLGA) inner layer and gelatin methacrylate (GelMA)/poly (ethylene glycol) diacrylate (PEGDA) outer layer was fabricated using a two-stage molding method for bile duct regeneration. Further, induced mesenchymal stem cells (MSC)-derived cholangiocyte-like cells were embedded in the outer layer during fabrication. The inner layer of PLGA offered adequate mechanical strength for the scaffold, and the outer layer of GelMA/PEGDA provided excellent biocompatibility and conditions for the MSCs and their induced differentiation. Moreover, cholic acid and its derivates are believed to induce MSC-cholangiocyte differentiation in two-dimensional culture and could affect the MSCs transforming to cholangiocyte-like cells in the hydrogel. Induced-MSC-laden GelMA/PEGDA-PLGA dual-layer tubular scaffold and PLGA single-layer scaffold were transplanted into animal models for assessing the repair effect on bile duct injury. After 12 wk, induced-MSC-laden dual-layer tubular scaffold promoted bile duct repairing and enhanced more intact biliary epithelium regenerating compared to PLGA single-layer scaffold. Therefore, the induced-MSC-laden dual-layer tubular scaffold with superior biocompatibility and distinct function of inducing differentiation exerted a satisfactory effect on bile duct regeneration and could provide an ideal option for the clinical treatment of bile duct injury in the future.

Background Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Costimulatory molecules have been proven to be the foundation of immunotherapy. However, the potential roles of costimulatory molecule genes (CMGs) in HCC remain unclear. Our study is aimed to develop a costimulatory molecule-related gene signature that could evaluate the prognosis of HCC patients. Methods Based on The Cancer Gene Atlas (TCGA) database, univariate Cox regression analysis was applied in CMGs to identify prognosis-related CMGs. Consensus clustering analysis was performed to stratify HCC patients into different subtypes and compared them in OS. Subsequently, the LASSO Cox regression analysis was performed to construct the CMGs-related prognostic signature and Kaplan–Meier survival curves as well as ROC curve were used to validate the predictive capability. Then we explored the correlations of the risk signature with tumor-infiltrating immune cells, tumor mutation burden (TMB) and response to immunotherapy. The expression levels of prognosis-related CMGs were validated based on qRT-PCR and Human Protein Atlas (HPA) databases. Results All HCC patients were classified into two clusters based on 11 CMGs with prognosis values and cluster 2 correlated with a poorer prognosis. Next, a prognostic signature of six CMGs was constructed, which was an independent risk factor for HCC patients. Patients with low-risk score were associated with better prognosis. The correlation analysis showed that the risk signature could predict the infiltration of immune cells and immune status of the immune microenvironment in HCC. The qRT-PCR and immunohistochemical results indicated six CMGs with differential expression in HCC tissues and normal tissues. Conclusion In conclusion, our CMGs-related risk signature could be used as a prediction tool in survival assessment and immunotherapy for HCC patients.

Fowl adenoviruses (FAdVs), which are distributed worldwide, have caused considerable economic losses to poultry farms. Co-infection with FAdVs and other avian pathogens has been reported previously. However, the pathogenicity of different serotypes of FAdVs causing co-infection remains unclear. Herein, strain HN from FAdV species C serotype 4 (FAdV-4) and strain AH720 from species E serotype 8a (FAdV-8a) were used to assess the pathogenicity of their co-infection in specific-pathogen-free (SPF) chickens. Compared with chickens infected with FAdV-4 alone, those co-infected with FAdV-4 and FAdV-8a showed similar clinical symptoms, mortality rates and degree of tissue lesions, and notably decreased viral loads of HN. Conversely, the viral loads of AH720 increased markedly in the co-infection group compared with that in chickens infected with AH720 strain alone. Increased viral loads of AH720 in the liver were suspected to contribute to the pathogenicity of chickens co-infected with the HN and AH720 strains. This was further investigated by histopathology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining analyses. Collectively, these data indicated that co-infection with FAdV-4 and FAdV-8a suppresses the replication and proliferation of FAdV-4 but enhances the replication and proliferation of FAdV-8a in chicken liver. This study will provide valuable information for the further investigation of the interactions between FAdV-4 and FAdV-8a during co-infection.

Controlling soil erosion is beneficial to the conservation of soil resources and ecological restoration. Understanding the spatial distribution characteristics of soil erosion helps find the key areas for soil control projects and optimal scale for investing in a soil and water conservation project at the lowest cost. This study aims to answer the question of how the spatial distribution of soil erosion in Hubei Province changed between 2000 and 2020. Moreover, how do the effects of natural factors and human activities on soil erosion vary over the years? What are the differences in landscape pattern characteristics and the spatial cluster of soil erosion at multiple administrative scales? We simulated the spatial distribution of soil erosion in Hubei province from 2000 to 2020 by the Chinese Soil Loss Equation model at three administrative scales. We investigated the relationship between soil erosion and driving factors by Geodector. We explored the landscape pattern and hotspots of land at different levels of soil erosion by Fragstat and hotspot analysis. The results show that: (1) The average soil erosion rate decreased from 2000 to 2020. Soil erosion is severe in the mountainous areas of western Hubei province, while it is less severe in the central plains. (2) Land-cover type, precipitation, and normalized difference vegetation index are the most influencing factors of soil erosion in 2000–2010, 2015, and 2020, respectively. (3) The aggregation index values at the town scale are higher than those at the city and county scales, while the fractal dimension index values at the town scale are lower, which indicates that soil erosion projects are most efficient when the project unit is ‘town’. (4) At the town scale, if the hotspot area (6.84% of the total area) is treated as the protection target, it can reduce 50.42% of the total soil erosion of Hubei province. Hotspots of soil erosion overlap with high erosion zones, mainly in the northwestern, northeastern, and southwestern parts of Hubei province in 2000, while the hotspots in northwestern Hubei disappear in 2020. In conclusion, land managers in Hubei should optimize the land-use structure, soil and water conservation in slope land, and eco-engineering controls at the town scale.

PurposeTo accurately stratify nasopharyngeal carcinoma (NPC) patients who were benefit from induction chemotherapy (IC) followed by chemoradiotherapy (CCRT), we established residual volume of lymph nodes during chemoradiotherapy based nomogram to predict survival for NPC patients.MethodsCox regression analysis were used to evaluate predictive effects of tumor volume parameters. Multivariate Cox regression analysis was used to identify the prognostic factors, and nomogram models were developed to predict survival of NPC patients receiving IC followed by CCRT.ResultsCompared with other tumor volumetric parameters, midRT GTVnd was the best predictive factor for OS (HR: 1.043, 95%CI: 1.031-1.055), PFS (HR: 1.040, 95%CI: 1.030- 1.051), and DMFS (HR: 1.046, 95%CI: 1.034 – 1.059) according to the HR of Cox regression analysis. Based on multivariate analysis, three nomograms included midRT GTVnd were constructed to predict 4-year survival. The C-index of nomograms for each survival endpoints were as follow (training cohort vs. validation cohort): 0.746 vs. 0.731 for OS; 0.747 vs. 0.735 for PFS; 0.768 vs. 0.729 for DMFS, respectively. AUC showed a good discriminative ability. Calibration curves demonstrated a consistence between actual results and predictions. Decision curve analysis (DCA) showed that the nomograms had better clinical predictive effects than current TNM staging system.ConclusionWe identified the best volumetric indicator associated with prognosis was the residual volume of lymph nodes at the fourth week of chemoradiotherapy for patients receiving IC followed by CCRT. We developed and validated three nomograms to predict specific probability of 4-year OS, PFS and DMFS for NPC patient receiving IC followed by CCRT.

Fowl adenovirus serotype 4 (FAdV-4), the causative agent of hepatitis-hydropericardium syndrome (HHS), distributed widely in the poultry farms in China. Hexon is one of the major capsid proteins associated with viral species or serotypes. However, the epitopes of Hexon protein remain largely unknown. In this study, a monoclonal antibody (mAb) specific to Hexon protein of FAdV-4, designated as 3G8, was generated. Subsequently, the linear peptide recognized by 3G8 was mapped and identified as 213AYGAYVK219 using a series of overlapping peptides generated from Hexon protein. Amino acid sequence analysis revealed that the epitope recognized by 3G8 was highly conserved across all the FAdVs. The epitope was immunogenic and could be recognized by FAdV-4 positive chicken serum samples. These findings will enrich our knowledge regarding the epitope on Hexon and provide valuable information for further characterization of the antigenicity of Hexon protein.

The systemic immune-inflammatory index (SII) and derived neutrophil-lymphocyte ratio (dNLR) are novel indexes that simultaneously reflect the host inflammatory and immune status and have prognostic value in some cancers. SII was associated with major cardiovascular events in coronary artery disease patients who received percutaneous coronary intervention (PCI). However, dNLR correlations with clinical outcomes in acute coronary syndrome (ACS) patients undergoing PCI remain unclear. This study aimed to elucidate the predictive values of SII and dNLR on the long-term prognosis of patients with ACS undergoing PCI. In total, 1,553 ACS patients undergoing PCI were consecutively enrolled from January 2016 to December 2018. The subjects were divided into high and low SII and dNLR groups for comparison (high vs. low). The SII and dNLR cutoff values for predicting major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves, and Kaplan-Meier curves and Cox regression models were used for survival analyses. The endpoint was a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. The Kaplan-Meier curves showed that a higher SII or dNLR value was associated with a higher risk of MACE (all P < 0.001). Multivariate Cox regression models showed that SII (hazard ratio [HR]: 2.545; 95% confidence interval [CI]: 1.416-4.574; P = 0.002) and dNLR (HR: 2.610, 95% CI: 1.454-4.685, P = 0.001) were independent predictors for MACE. dNLR may be a suitable laboratory marker to identify high-risk ACS patients after PCI.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective therapeutic targets. Immunotherapy is considered as a novel treatment strategy for TNBC. However, only some patients could benefit from the treatment. Limited studies have comprehensively explored expression patterns and prognostic value of immune checkpoint genes (ICGs) in TNBC. In this study, we downloaded relevant ICGs expression profiles and clinical TNBC data from the Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was employed to develop a multi-gene signature for predicting the prognostic outcome. PDCD1, PDCD1LG2 and KIR3DL2 were identified as hub genes and incorporated into the model. This gene signature could stratify patients into two prognostic subgroups, and unfavorable clinical outcomes were observed in high-risk patients. The predictive performance was assessed by the receiver operating characteristic curves. Moreover, we also analyzed differences in immune status and therapeutic response between both groups. This novel gene signature may be served as a robust prognostic marker, but also an indicator reflecting immunotherapy response.

Objective This study aimed to investigate the predictive value of inflammatory cells in peripheral blood on the prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods Patients (n=1558) were consecutively enrolled and the median follow-up was 1142 days. Patients were divided into the major adverse cardiac events (MACE) 1 group (n=63) (all-cause mortality [n=58] and rehospitalization for severe heart failure [n=5], no MACE1 group (n=1495), MACE2 group (n=38) (cardiac mortality [n=33] and rehospitalization for severe heart failure [n=5]), and no MACE2 group (n=1520). The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were analyzed. Results The NLR, MLR, and PLR were higher in the MACE groups than in the no MACE groups. Different subsets of inflammatory cells had similar diagnostic values for MACE. Kaplan–Meier curves showed that the survival time gradually decreased with an increase in the degree of risk as determined by the NLR, MLR, and PLR. The risk of MACE was highest in the extremely high-risk group. Conclusion Peripheral blood inflammatory cell subsets can predict MACE in patients with ACS undergoing PCI. These cell subsets could be important laboratory markers for the prognosis and clinical treatment of these patients.

Intracranial atherosclerotic stenosis (ICAS) is one of most common causes of stroke; it has the highest rate of recurrence compared with other aetiologies.1 ICAS is especially more prevalent among the Asians.2 The results of the Chinese Intracranial Atherosclerosis Study indicated that the prevalence of symptomatic ICAS (sICAS) is as high as 46%.1 The 1-year stroke recurrence rate with sICAS is reported to be 12.2% and 15%.3 4 We understand, the following pathological reasons could account for the high recurrence rate in sICAS. First, patients with ICAS are prone to encounter hypoperfusion haemodynamics, especially under poor collateral conditions.5 Studies on the association of blood pressure (BP) control in the acute stage and clinical outcomes are contradictory, supporting this hypothesis.6 Second, plaques in stenotic arteries are usually highly vulnerable (due to large lipid cores, thin fibrous caps and intraplaque haemorrhage).7 These plaques are prone to rupture into downstream arteries, leading to embolic stroke in the territory of the responsible artery.5 Furthermore, these patients are often comorbid with heightened risk factors strongly correlated with stroke recurrence, including hypertension, metabolic disorders, dyslipidaemia.8 Therefore, there is an urgent need to standardise assessment and management of sICAS. The treatment of sICAS nowadays primarily focuses on secondary prevention to reduce stroke recurrence. Therapeutic methods include antiplatelet therapy, interventional therapy and control of risk factors.9 Two milestone trials, the Warfarin Aspirin Symptomatic Intracranial Disease (WASID)3 Trial and the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS)4 Trial aim to provide an updated strategy for clinical practice. The WASID Trial, with a double-blind, multicentre, randomised control clinical trial design, aimed to evaluate the efficacy and safety of warfarin over aspirin among patients with 50%–99% degree of ICAS. Aspirin proved to be equally efficient …

Glucosamine (GlcN) has been widely used to reduce joint pain and osteoarthritis progression, but the efficacy of GlcN remains controversial because of the low GlcN concentration reaching the articular cavity. The aim of this study is to provide an effective approach of GlcN delivery to a target site using photocrosslinkable methacrylated gelatin (GelMA)-based hydrogels, where GlcN could be gradually released during the degradation of the GelMA hydrogel. Herein, GlcN was acrylated as the acryloyl glucosamine (AGA) and covalently grafted to GelMA, and more than 87.7% of 15% (w/v) GelMA hydrogel was grafted with AGA. Moreover, in vitro outgrowth and apoptosis assay of bone marrow stem cells (BMSCs) demonstrated that the GelMA-AGA hydrogels had better biocompatibility, larger cell attachment, and higher cell viability than pure GlcN and AGA materials. Also, 15% (w/v) GelMA-AGA hydrogel was injected into the defect site for in vivo rabbit cartilage repair. Compared with oral administration of pure GlcN and injection of pure GelMA, the repaired cartilages using GelMA-AGA hydrogels had the smoothest surface of the defect site, filling more than 95% defect bulk. The similar content of glycosaminoglycans to the native tissue and the maximum amount of type II collagen was found in the repaired cartilage using GelMA-AGA hydrogels, indicating the outgrowth of hyaline cartilage.

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or CDK6 significantly overcomes the resistance of luminal breast cancer cells to AKT inhibitors in vitro and in vivo. Our study reports the involvement of BRD4/FOXO3a/CDK6 axis in AKTi resistance and provides potential therapeutic strategies for treating resistant breast cancer., The molecular mechanism underlying the resistance of AKT inhibitors in breast cancer is still elusive. Here, the authors demonstrate that BRD4/FOXO3a axis upregulates CDK6 promoter activity to promote resistance to AKT inhibition in breast cancer cells and that blocking the action of CDK6 re-sensitizes resistant cancer cells to growth inhibition.

Tumor microenvironment-induced ultrasmall nanodrug generation (TMIUSNG) is an unprecedented approach to overcome the drug penetration barriers across complex biological systems, poor circulation stability and limited drug loading efficiency (DLE). Herein, a novel strategy was designed to synthesize metal-organic nanodrug complexes (MONCs) through supramolecular coassembly of photosensitizer sinoporphyrin sodium, chemotherapeutic drug doxorubicin and ferric ions. Compared with the free photosensitizer, MONCs produced 3-fold more reactive oxygen species (ROS) through the energy transfer-mediated fluorescence quenching. Remarkably, the self-delivering supramolecular MONCs with high DLE acted as a potent ultrasmall-nanodrug generator in response to the mild acidic tumor microenvironment to release ultrasmall nanodrugs (5-10 nm in diameter) from larger parental nanoparticles (140 nm in diameter), which in turn enhanced the intratumor permeability and therapeutic efficacy. The key mechanism of MONC synthesis was proposed, and we, for the first time, validated the generation of supramolecular scaffold intermediates between MONCs' assembly/disassembly states, as well as their involvement in multidrug ligands interactions. This proof-of-concept TMIUSNG strategy provides a foundation for the rational design of analogous carrier-free nanotheranostics through the combination of multiple therapeutic agents and metal ions with imaging functions.

Background Single intrauterine death in twin pregnancy has become a relatively frequent complication of twin pregnancy. Preterm delivery is one of the complications with high incidence, and is closely related to the prognosis of the surviving fetus. However, studies about preterm delivery related to single intrauterine death are limited. The purpose of this paper is to analyze the factors associated with preterm birth in twins after single intrauterine death.Methods This was a case-control study of single intrauterine death in twins delivered at Shengjing Hospital over a 12-year period, from January 1, 2008, to November 30, 2020. We classified these cases into the preterm birth group and full-term birth group according to gestational age at birth. We selected age, gestational age at Single intrauterine death, and parity, etc, as related factors of the preterm birth group. Logistic regression analyses were performed to determine the relevance and importance of related factors and their association with preterm birth. We divided the preterm birth group into four smaller groups according to gestational age at single intrauterine death (14-19 weeks, 20-24 weeks, 25-30 weeks, and 31-36 weeks) and compared them. To exclude human intervention, we analyzed the spontaneous delivery cases as well.Results The analysis included 175 twins (mean [SD] gestational age at single intrauterine death, 27.0 [5.8] weeks; mean [SD] gestational age at birth, 33.8 [3.2] weeks ) with single intrauterine death. A total of 139 (79.4%) were cases of preterm birth. A significant risk factor associated with preterm birth was gestational age at single intrauterine death (odds ratio [OR], 2.89; 95% CI, 1.90-4.39). We found that the 14- to 19-week age group had the oldest gestational age at birth (37.25 [1.29]weeks ). The length of gestation in 14-19 weeks group, 20-24 weeks group, 25-30 weeks group and 31-36 weeks group were 20.5 weeks, 11.0 weeks, 4.77 weeks and 1.12 weeks respectivelyConclusion The fetus’ gestational age at single intrauterine death was a risk factor for preterm birth in their twin. The length of gestation was inversely proportional to increasing gestational age at single intrauterine death.

Background and Purpose: The morbidity and mortality of subarachnoid hemorrhage in China have improved due to clear diagnosis, active treatment, and better management of accompanying complications. Considering these improvements, it is not clear if the previously identified independent predictors of negative outcomes have changed. The aim of this study was to identify the independent predictors of being discharged home from hospital in subarachnoid hemorrhage patients. Methods: Data from subarachnoid hemorrhage patients who were admitted to participating hospitals in the Chinese Stroke Center Alliance between June 2015 and November 2017 were analyzed. Univariate and multivariate logistic regression models were generated to identify independent predictors of patient discharged home from hospital. Results: A total of 10763 patients (median age 60 yrs, female 59.1%) were analyzed. In-hospital mortality was observed in 327 (3%) patients. At discharge, 7652 (73.3%) patients returned home from hospital. The independent predictors of being discharged home were systolic blood pressure (odds ratio [OR], 0.996; 95% confidence interval [CI], 0.994-0.998; P P P P= 0.0476), need for cerebrospinal fluid diversion (OR, 0.039; 95% CI, 0.014-0.109; P Conclusions: These data suggest that endovascular and joint intervention are associated with favorable outcomes, whereas potentially modifiable risk factors of poorly controlled blood pressure, glucose level, seizure, and pulmonary complications are associated with unfavorable outcomes. Understanding the reasons why patients requiring cerebrospinal fluid diversion have 25.781-fold higher adjusted odds of poor outcome at discharge may be beneficial.

BackgroundEvidence from prevailing studies show that hepatocellular carcinoma (HCC) is among the top cancers with high mortality globally. Gene regulation at post-transcriptional level orchestrated by RNA-binding proteins (RBPs) is an important mechanism that modifies various biological behaviors of HCC. Currently, it is not fully understood how RBPs affects the prognosis of HCC. In this study, we aimed to construct and validate an RBP-related model to predict the prognosis of HCC patients.MethodsDifferently expressed RBPs were identified in HCC patients based on the GSE54236 dataset from the Gene Expression Omnibus (GEO) database. Integrative bioinformatics analyses were performed to select hub genes. Gene expression patterns were validated in The Cancer Genome Atlas (TCGA) database, after which univariate and multivariate Cox regression analyses, as well as Kaplan-Meier analysis were performed to develop a prognostic model. Then, the performance of the prognostic model was assessed using receiver operating characteristic (ROC) curves and clinicopathological correlation analysis. Moreover, data from the International Cancer Genome Consortium (ICGC) database were used for external validation. Finally, a nomogram combining clinicopathological parameters and prognostic model was established for the individual prediction of survival probability.ResultsThe prognostic risk model was finally constructed based on two RBPs (BOP1 and EZH2), facilitating risk-stratification of HCC patients. Survival was markedly higher in the low-risk group relative to the high-risk group. Moreover, higher risk score was associated with advanced pathological grade and late clinical stage. Besides, the risk score was found to be an independent prognosis factor based on multivariate analysis. Nomogram including the risk score and clinical stage proved to perform better in predicting patient prognosis.ConclusionsThe RBP-related prognostic model established in this study may function as a prognostic indicator for HCC, which could provide evidence for clinical decision making.

Objectives: This study aims to investigate whether the machine learning algorithms could provide an optimal early mortality prediction method compared with other scoring systems for patients with cerebral hemorrhage in intensive care units in clinical practice.Methods: Between 2008 and 2012, from Intensive Care III (MIMIC-III) database, all cerebral hemorrhage patients monitored with the MetaVision system and admitted to intensive care units were enrolled in this study. The calibration, discrimination, and risk classification of predicted hospital mortality based on machine learning algorithms were assessed. The primary outcome was hospital mortality. Model performance was assessed with accuracy and receiver operating characteristic curve analysis.Results: Of 760 cerebral hemorrhage patients enrolled from MIMIC database [mean age, 68.2 years (SD, ±15.5)], 383 (50.4%) patients died in hospital, and 377 (49.6%) patients survived. The area under the receiver operating characteristic curve (AUC) of six machine learning algorithms was 0.600 (nearest neighbors), 0.617 (decision tree), 0.655 (neural net), 0.671(AdaBoost), 0.819 (random forest), and 0.725 (gcForest). The AUC was 0.423 for Acute Physiology and Chronic Health Evaluation II score. The random forest had the highest specificity and accuracy, as well as the greatest AUC, showing the best ability to predict in-hospital mortality.Conclusions: Compared with conventional scoring system and the other five machine learning algorithms in this study, random forest algorithm had better performance in predicting in-hospital mortality for cerebral hemorrhage patients in intensive care units, and thus further research should be conducted on random forest algorithm.

There has been increasing concern about the health effects of air pollution in China, and many measures have been implemented to control air pollution. To investigate the impacts of air quality improvement on mortality from non-accidental causes (NAD), cardiovascular disease (CD), and respiratory disease (RD), a longitudinal comparative study was conducted in Beijing. This study investigated the effects of air pollutants on outcomes across five periods (stages 1–5). Health effect data from stage1–5 (1990–2013) were obtained through a systematic literature search of studies published before 2021. Daily atmospheric pollutant, meteorological, and cause-specific death data were collected to determine the effects in stage 5 (2015–2017). Poisson generalized additive models were used to analyze the associations between short-term exposure to air pollutants and mortality. Random-effects meta-analysis models were used to estimate the pooled effects at each stage. The effects of changes in air quality were analyzed through a difference-in-differences approach. Our results indicate that the absolute change of concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter with aerodynamic diameter≤ 10 μm (PM10) and≤ 2.5 μm (PM2.5) decreased by up to 42%, 10%, 33%, and 15% (stage 5), respectively. The effects of SO2 on deaths from CD and RD decreased by up to 2.76% and 1.43% (stage 3). The effects of NO2 on mortality from NAD, CD, and RD decreased by up to 0.39%, 0.74%, and 0.37% (stage 5). The effects of PM10 on death decreased by up to 0.11% (stage 3). The effects of PM2.5 on deaths from CD and RD decreased by up to 0.33% and 0.13% (stage 5). The results indicate that continued improvements in air quality have reduced the acute impact of air pollutants on population health.

Background: The atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, and monocyte-to-lymphocyte ratio (MLR) are strongly associated with atherogenesis of the coronary artery. This study aimed to investigate the association of the AIP, TyG index, and MLR with subclinical coronary artery disease (CAD) and evaluate their ability to predict subclinical CAD.Methods: A total of 697 asymptomatic patients were enrolled in this study and assigned to the subclinical CAD group (n=332) and control group (n=365). The clinical data, coronary artery calcification score, and calculated AIP, TyG index, and MLR were collected by graduate students in the cardiology division. Multivariate logistic regression models were set up to assess the risk factors for subclinical CAD.Results: The AIP, TyG index and MLR values were higher in the subclinical CAD group than in the control group (all PConclusions: The AIP, TyG index and MLR are independent risk factors for subclinical CAD, which can be useful for improving the diagnosis and prevention of CAD.

Keywords: phenolic acids, antimicrobial, antioxidant