Development and validation of a nomogram for predicting cognitive frailty in patients on maintenance haemodialysis.

AIMS: This study aimed to construct a nomogram for predicting the risk of cognitive frailty in patients on maintenance haemodialysis. DESIGN: An explorative cross-sectional design was adopted. METHODS: From April 2022 to July 2022, 496 participants were recruited from five haemodialysis centres in Qingdao, Shandong Province, China. Participants with cognitive frailty were screened by Frailty Phenotype scale and Mini-Mental State Examination. Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression were utilized to determine predictors. The predictive performance of the nomogram was validated by calibration and discrimination. Decision curve analysis was used to assess clinical utility. Internal validation was implemented using 1000 bootstrap samples to mitigate overfitting. RESULTS: The prevalence of cognitive frailty was 17.5% (n = 87). Six risk predictors, namely health empowerment, alexithymia, age, educational level, marital status and dialysis vintage, were screened and used to develop a nomogram model. The nomogram had satisfactory discrimination and calibration, and decision curve analysis revealed considerable clinical utility. CONCLUSIONS: A nomogram incorporated with the six risk predictors was developed, and it exhibited excellent prediction performance. The nomogram may strengthen the effective screening of patients at high risk of cognitive frailty. IMPACT: This study established a tool for healthcare staff to predict cognitive frailty probability and identify risk factors in patients on maintenance haemodialysis. The nomogram can meet the needs of personalized care and precision medicine simultaneously. PATIENT OR PUBLIC CONTRIBUTION: Data were collected from patients on maintenance haemodialysis by using questionnaire survey. REPORTING METHOD: STROBE checklist was used.

DCPNet: a dual-channel parallel deep neural network for high quality computer-generated holography.

Recent studies have demonstrated that a learning-based computer-generated hologram (CGH) has great potential for real-time, high-quality holographic displays. However, most existing algorithms treat the complex-valued wave field as a two-channel spatial domain image to facilitate mapping onto real-valued kernels, which does not fully consider the computational characteristics of complex amplitude. To address this issue, we proposed a dual-channel parallel neural network (DCPNet) for generating phase-only holograms (POHs), taking inspiration from the double phase amplitude encoding method. Instead of encoding the complex-valued wave field in the SLM plane as a two-channel image, we encode it into two real-valued phase elements. Then the two learned sub-POHs are sampled by the complementary 2D binary grating to synthesize the desired POH. Simulation and optical experiments are carried out to verify the feasibility and effectiveness of the proposed method. The simulation results indicate that the DCPNet is capable of generating high-fidelity 2k POHs in 36 ms. The optical experiments reveal that the DCPNet has excellent ability to preserve finer details, suppress speckle noise and improve uniformity in the reconstructed images.

High-Resolution Vessel Wall MRI in Assessing Postoperative Restenosis of Intracranial Atherosclerotic Disease Before Drug-Coated Balloon Treatment: An Outcome Prediction Study.

BACKGROUND: Postoperative restenosis frequently occurs in intracranial atherosclerotic disease (ICAD) patients after drug-coated balloon (DCB) treatment. However, high-risk plaques associated with postoperative restenosis remain to be explored. PURPOSE: To assess whether high-resolution vessel wall MRI (HR-VWI) contributes to the identification of high-risk plaques associated with postoperative restenosis before DCB treatment. STUDY TYPE: Retrospective. SUBJECTS: A total of 70 patients with ICAD who underwent DCB treatment. FIELD STRENGTH/SEQUENCE: 3.0 T; magnetic resonance angiography, HR-VWI. ASSESSMENT: All patients underwent HR-VWI examination prior to DCB treatment. Digital subtraction angiography (DSA) measurement was assessed 6 months (±1 month) after operation to determine the vessel restenosis, classifying patients into three groups of no stenosis, mild stenosis (<50%), and restenosis (>50%). Clinical factors and HR-VWI characteristics, including vessel and lumen area at maximal lumen narrowing (MLN), plaque area and length, degree of stenosis, plaque burden, remodeling index, and enhancement amplitude, were compared among three groups. Clinical factors and HR-VWI characteristics were separately evaluated for the association with postoperative restenosis. STATISTICAL TESTS: Kolmogorov-Smirnov test, intra-class correlation coefficient, Kruskal Wallis H test, Mann-Whitney U test, receiver operating characteristic (ROC) curve, multivariable linear regression analysis. P-values <0.05 was considered statistically significant. RESULTS: During the follow-up DSA measurement, 13 lesions (18.5%) showed restenosis. With HR-VWI, significant differences among three groups were observed in plaque length, lumen area of MLN, degree of stenosis, enhancement amplitude, and plaque burden. In ROC analysis, plaque length (area under the curve [AUC] = 0.809), and enhancement amplitude (AUC = 0.880) provided higher efficacy in identification of high-risk plaques associated with postoperative restenosis than degree of stenosis (AUC = 0.746) and plaque burden (AUC = 0.759). Multivariable linear regression analysis showed that plaque length and enhancement amplitude were independent prognostic factors of postoperative restenosis. DATA CONCLUSION: HR-VWI has the potential to identify high-risk plaques in ICAD patients before DCB treatment. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Leisure crafting and work engagement among Chinese ICU nurses: The multiple mediation effect of recovery experience and humanistic care ability.

AIMS: Based on the conservation of resources theory, this study explored the intermediary role of intensive care unit (ICU) nurses' recovery experience and humanistic care ability between leisure crafting and work engagement. BACKGROUND: As the ICU is an important life-saving department, the level of work engagement of nurses directly affect the quality of life and health outcomes of patients. Actively seeking countermeasures to improve the work engagement level of ICU nurses is of great significance to enhancing the nursing quality of the ICU. According to the theory of resource conservation, the resources owned by individuals are limited and must be replenished promptly and effectively to maintain relatively stable physical, mental, and working states. Therefore, determining ways for ICU nurses to supplement the consumed resources effectively and efficiently in a limited time to maintain a high level of work engagement is the main concern of this study. METHODS: In this cross-sectional study from January 2023 to March 2023, 478 ICU nurses were recruited by convenience sampling. The survey tools included the Leisure Crafting Scale, the Utrecht Work Engagement Scale-9, the Caring Ability Inventory, and the Recovery Experience Questionnaire. Descriptive data and Pearson correlation coefficients were analyzed via SPSS 26.0 (IBM Corp.). PROCESS v4.0 (by Andrew F. Hayes) Macro Model 6 was applied to analyze the serial multiple mediator models. We used the STROBE checklist to report the results. RESULTS: First, the results showed that leisure crafting, humanistic care ability, and recovery experience were positively correlated with work engagement. Second, recovery experience and humanistic care ability played a partially mediating role between leisure crafting and work engagement, respectively. Third, recovery experience and humanistic care ability also had a serial mediation effect between leisure crafting and work engagement. CONCLUSION: The findings of the study indicated that improving nurses' active control of leisure time may have particularly positive effects on ICU nurses' work engagement through increasing recovery experience and humanistic care ability. IMPLICATIONS FOR NURSING AND NURSING POLICY: Administrators can formulate intervention measures to improve the leisure crafting level of ICU nurses, promote work-life balance, which enhances recovery and supports engagement with patient-focused humanistic care, and have a positive impact on the work engagement of ICU nurses.

Magnetic resonance spectroscopy associations with clinicopathologic features of estrogen-dependent endometrial cancer.

BACKGROUND: We studied the magnetic resonance spectroscopy (MRS) associations with clinicopathologic features of estrogen-dependent endometrial cancer (type I EC). METHODS: Totally 45 patients with type I EC who underwent preoperative multi-voxel MRS at 3.0 T were enrolled. The mean ratio of the Cho peak integral to the unsuppressed water peak integral (Cho/water) of the tumor was calculated. The Cho/water and apparent diffusion coefficient (ADC) of type I EC with and without local invasion, as well as with different levels of Ki-67 staining index (SI) (≤ 40% and > 40%), were compared. Correlation test was used to examine the relationship of Cho/water, as well as mean ADC, with Ki-67 SI, tumor stage, and tumor grade. RESULTS: The mean Cho/water of EC with Ki-67 SI ≤ 40% (2.28 ± 0.93) × 10-3 was lower than that with Ki-67 SI > 40% (4.08 ± 1.00) × 10-3 (P < 0.001). The mean Cho/water of EC with deep and superficial myometrial invasion was (3.41 ± 1.26) × 10-3 and (2.43 ± 1.11) × 10-3, respectively (P = 0.011). There was no significant difference in Cho/water between type I EC with and without cervical invasioin ([2.68 ± 1.00] × 10-3 and [2.77 ± 1.28] × 10-3, P = 0.866). The mean Cho/water of type I EC with and without lymph node metastasis was (4.02 ± 1.90) × 10-3 and (2.60 ± 1.06) × 10-3, respectively (P = 0.014). The Cho/water was positively correlated with the Ki-67 SI (r = 0.701, P < 0.001). There were no significant differences in ADC among groups (all P > 0.05). CONCLUSION: MRS is helpful for preoperative assessment of clinicopathological features of type I EC.

Assessment of postpartum haemorrhage for placenta accreta: Is measurement of myometrium thickness and dark intraplacental bands using MRI helpful?

BACKGROUND: This study aimed to investigate the predictive values of magnetic resonance imaging (MRI) myometrial thickness grading and dark intraplacental band (DIB) volumetry for blood loss in patients with placenta accreta spectrum (PAS). METHODS: Images and clinical data were acquired from patients who underwent placenta MRI examinations and were diagnosed with PAS from March 2015 to January 2021. Two radiologists jointly diagnosed, processed, and analysed the MR images of each patient. The analysis included MRI-based determination of placental attachment, as well as myometrial thickness grading and DIB volumetry. The patients included in the study were divided into three groups according to the estimated blood loss volume: in the general blood loss (GBL) group, the estimated blood loss volume was < 1000 ml; in the massive blood loss (MBL) group, the estimated blood loss volume was ≥ 1000 ml and < 2000 ml; and in the extremely massive blood loss (ex-MBL) group, the estimated blood loss volume was ≥ 2000 ml. The categorical, normally distributed, and non-normally distributed data were respectively analysed by the Chi-square, single-factor analysis of variance, and Kruskal-Wallis tests, respectively. The verification of correlation was completed by Spearman correlation analysis. The evaluation capabilities of indicators were assessed using receiver operating characteristic curves. RESULTS: Among 75 patients, 25 were included in the GBL group, 26 in the MBL group, and 24 in the ex-MBL group. A significant negative correlation was observed between the grade of myometrial thickness and the estimated blood loss (P < 0.001, ρ = - 0.604). There was a significant positive correlation between the volume of the DIB and the estimated blood loss (P < 0.001, ρ = 0.653). The areas under the receiver operating characteristic curve of the two MRI features for predicting blood loss ≥ 2000 ml were 0.776 and 0.897, respectively. CONCLUSIONS: The grading and volumetric MRI features, myometrial thickness, and volume of DIB, can be used as good prediction indicators of the risk of postpartum haemorrhage in patients with PAS.

Social support and sleep quality in patients with stroke: The mediating roles of depression and anxiety symptoms.

BACKGROUND: Research has demonstrated that higher social support is associated with better psychological health, quality of life, cognition, activities of daily living and social participation, but the relationship between social support and sleep quality remains unknown. AIMS: This study aimed to assess the incidence of poor sleep quality, clarify the relationship between social support and sleep quality amongst stroke patients and determine whether anxiety and depression symptoms mediate this relationship. METHODS: We conducted a quantitative, cross-sectional study involving 238 patients with stroke (median age of 61 [range 29-87] years, 68.1% male) recruited from a comprehensive tertiary care hospital between September 2019 and January 2020. A self-administered, structured questionnaire was used for the survey. The mediating effect of anxiety and depression symptoms was assessed using the bootstrap method via Model 4 (parallel mediation) of the SPSS PROCESS macro. RESULTS: Results showed that the incidence of poor sleep quality amongst stroke patients was 65%. Mediation analysis showed that social support exerted significant direct effects on sleep quality, and anxiety and depression symptoms mediated the relationship between social support and sleep quality. CONCLUSION: Measures should be taken to enhance social support to improve the sleep quality of stroke patients.

Applications of System Dynamics Models in Chronic Disease Prevention: A Systematic Review.

INTRODUCTION: Chronic disease is a serious health problem worldwide. Given that health care resources are limited, a comprehensive, effective, and affordable way is needed to provide insights to prevent chronic diseases. System dynamics models provide a comprehensive and systematic method that can predict results over time. These models can simulate and predict appropriate prevention measures for chronic diseases to determine the best practice. METHODS: Two researchers (Y.W., B.H.) independently searched databases (PubMed, Web of Science, Scopus, and Embase) for full-text articles published from January 2000 through February 2021. A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) 2020-compliant search was carried out to review system dynamics models of chronic disease prevention. A total of 34 articles were included in our study. RESULTS: We divided the prevention measures of system dynamics models into 2 main categories: upstream prevention and downstream prevention. Upstream prevention measures include lifestyle (eg, tobacco control, balanced diet, mental health, moderate exercise), obesity prevention, and social factors. Downstream prevention measures include clinical treatment of chronic diseases. Results showed that effective upstream prevention measures could reduce the prevalence of chronic diseases, and downstream prevention measures could reduce the incidence of complications, improve quality of life, prolong life, save medical costs, and reduce mortality. CONCLUSION: To our knowledge, our systematic review is the first to evaluate the application of system dynamics models in preventing chronic diseases. Such models can provide effective simulations. Hence, we can use system dynamics models to design and implement effective prevention measures for people with chronic diseases.

Relationship between illness perception, fear of progression and quality of life in interstitial lung disease patients: A cross-sectional study.

AIMS AND OBJECTIVES: This study aimed to investigate whether fear of progression mediates the association between illness perception and quality of life among interstitial lung disease patients. BACKGROUND: So far, the physiological treatment of interstitial lung disease is limited. In addition to immunosuppressants such as glucocorticoids, two anti-fibrosis drugs (pirfenidone and nintedanib) have shown moderately beneficial effects on slowing the progression of interstitial lung disease fibrosis. However, none of these drugs has shown reliable or strong beneficial effects on improving quality of life. Psychological care and mental health support strategies focusing on improving patients' quality of life are particularly important. DESIGN: A cross-sectional study. METHODS: A convenience sample of patients suffering from interstitial lung disease were enrolled from August to December 2019. Data including sociodemographic and clinical characteristics, illness perception, fear of progression and quality of life were collected. The descriptive analysis and Pearson correlations were analysed by SPSS 26.0 (IBM Corp.). PROCESS v3.4 (by Andrew F. Hayes) macro was applied to analyse the mediating effects. We used the STROBE checklist to report the results. RESULTS: Both illness perception and fear of progression were correlated with quality of life. Fear of progression mediated the association between illness perception and quality of life. The indirect effect was 0.121, and the proportion of intermediary effect in the main effect was 26.36%. CONCLUSION: Interstitial lung disease patients experience relatively poor quality of life and fear of progression exerts a mediating role between illness perception and quality of life. RELEVANCE TO CLINICAL PRACTICE: This study alerts medical staff to pay attention to negative illness perception and excessive fear, which is helpful to formulate effective interventions to manage interstitial lung disease patients' quality of life.

Nurses' behaviours towards physical restraint use in the ICU: A descriptive qualitative study.

AIMS AND OBJECTIVES: The study aims to explore and describe nurses' behaviours towards physical restraint (PR) use in intensive care units (ICUs) and identify key characteristics of these experiences. BACKGROUND: Patients within the ICU are always vulnerable, which requires a thoughtful deliberation when employing PR in ethically laden situations. Considering that the qualitative study on nurses' behaviours towards PR use in ICUs is limited, a deep understanding of how nurses reason and restrict patients is necessary before developing a minimizing programme in hospitals. METHODS: A descriptive qualitative study was conducted in this paper. Data were collected by 24 semistructured, in-depth and individual interviews about PR, where 24 nurses were drawn from six ICUs of four hospital settings from a comprehensive tertiary care hospital in Qingdao. The QSR NVivo 11.0 software program was used to manage the interview data, and data analysis was guided by the Qualitative Analysis Guide of Leuven. The checklist of Consolidated Criteria for Reporting Qualitative Studies was followed as a guideline in reporting the study. RESULTS: Regarding PR, nurses' behaviours start with a hazard perception, followed by hesitation about whether to restrict the patient. They would usually decide to apply PR when they think that no other choice to control the situation is available. Then, they would reflect on and rationalize their behaviours. Nurses, intensivists, patients and their families participate in and affect this process directly or indirectly. CONCLUSIONS: Nurses' behaviours towards PR use comprise a series of complex processes centred on safety. Nurses' decision making should be performed with the participation of intensivists, patients and family caregivers.

Versatile Functionalization of Ferritin Nanoparticles by Intein-Mediated Trans-Splicing for Antigen/Adjuvant Co-delivery.

Self-assembling protein nanoparticles are extensively and increasingly engineered to integrate adjuvants with antigens to elicit potent and long-term immunity due to uniform architecture, inherent biocompatibility, and excellent plasticity. However, functionalization of nanoparticles by surface tailoring has two common problems: (1) disassembly caused by loaded cargoes; and (2) an adjuvant that is inconvenient to co-deliver with an antigen by genetic fusion. Here, we report an intein-mediated trans-splicing approach that overcomes the detrimental effects of loaded proteins on ferritin nanoparticle stability and allows concurrent display of antigen and adjuvant in a facile, efficient, and site-specific manner. An immunization study with an epitope-based model antigen reveals that antigen and adjuvant co-delivery nanoparticles induce a more potent protective immunity than other formulations do. Our results demonstrate that protein engineering represents an intriguing approach for antigen/adjuvant co-delivery to potentiate antigen-associated immune responses.

Structure, Immunogenicity, and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid.

Enterovirus 71 (EV71) is the major causative agent of severe hand, foot, and mouth disease, which affects millions of young children in the Asia-Pacific region annually. In this study, we engineered a novel EV71 virus-like particle (VLP) that lacks VP4 (therefore designated VLPΔVP4) and investigated its structure, antigenicity, and vaccine potential. The cryo-electron microscopy (cryo-EM) structure of VLPΔVP4 was reconstructed to 3.71-Å resolution. Results from structural and biochemical analyses revealed that VLPΔVP4 resembles the end product of the viral uncoating process, the 80S empty capsid. VLPΔVP4 is able to elicit high-titer neutralizing antibodies and to fully protect mice against lethal viral challenge. Mechanistic studies showed that, at the cellular level, the anti-VLPΔVP4 sera exert neutralization effects at both pre- and postattachment stages by inhibiting both virus attachment and internalization, and at the molecular level, the antisera can block multiple interactions between EV71 and its key receptors. Our study gives a better understanding of EV71 capsid assembly and provides important information for the design and development of new-generation vaccines for EV71, and perhaps for other enteroviruses, as well.IMPORTANCE Enterovirus 71 (EV71) infection may lead to severe hand, foot, and mouth disease, with significant morbidity and mortality. Knowledge regarding EV71 particle assembly remains limited. Here, we report the generation and characterization of a novel EV71 virus-like particle that lacks the VP4 capsid subunit protein. This particle, termed VLPΔVP4, structurally mimics the 80S empty capsid, which is the end stage of EV71 uncoating. We further show that VLPΔVP4 exhibits desirable immunogenicity and protective efficacy in proof-of-concept studies. In addition, the inhibitory mechanisms of the VLPΔVP4-induced antibodies are unraveled at both the cellular and molecular levels. Our work provides the first evidence of picornaviral particle assembly in the complete absence of VP4 and identifies VLPΔVP4 as an improved EV71 vaccine candidate with desirable traits. These findings not only enhance our understanding of particle assembly and uncoating of picornaviruses, but also provide important information for structure-guided vaccine design for EV71 and other enteroviruses.

Beta-Propiolactone Inactivation of Coxsackievirus A16 Induces Structural Alteration and Surface Modification of Viral Capsids.

Beta-propiolactone (BPL) is an inactivating agent that is widely used in the vaccine industry. However, its effects on vaccine protein antigens and its mechanisms of action remain poorly understood. Here we present cryo-electron microscopy (cryo-EM) structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids at resolutions of 3.9 Å and 6.5 Å, respectively. Notably, both particles were found to adopt an expanded conformation resembling the 135S-like uncoating intermediate, with characteristic features including an opened 2-fold channel, the externalization of the N terminus of VP1 capsid protein, and the absence of pocket factor. However, major neutralizing epitopes are very well preserved on these particles. Further biochemical analyses revealed that BPL treatment impairs the abilities of CVA16 particles to bind to the attachment receptor heparan sulfate and to a conformation-dependent monoclonal antibody in a BPL dose-dependent manner, indicating that BPL is able to modify surface-exposed amino acid residues. Taken together, our results demonstrate that BPL treatment may induce alteration of the overall structure and surface properties of a nonenveloped viral capsid, thus revealing a novel mode of action of BPL.IMPORTANCE Beta-propiolactone (BPL) is commonly used as an inactivating reagent to produce viral vaccines. It is recognized that BPL inactivates viral infectivity through modification of viral nucleic acids. However, its effect on viral proteins remains largely unknown. Here, we present high-resolution cryo-EM structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids, which reveals an expanded overall conformation and characteristic features that are typical for the 135S-like uncoating intermediate. We further show that the BPL concentration affects the binding of inactivated CVA16 particles to their receptor/antibody. Thus, BPL treatment can alter the overall structure and surface properties of viral capsids, which may lead to antigenic and immunogenic variations. Our findings provide important information for future development of BPL-inactivated vaccines.

Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody.

Enterovirus 71 (EV71) is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM) single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3) of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2), the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection.

Clinical value of peripheral blood microRNA detection in evaluation of SOX regimen as neoadjuvant chemotherapy for gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy has been widely applied in treating advanced gastric cancer (GC). However, little research has been conducted on evaluating the effect of neoadjuvant chemotherapy. Purpose of this study was to evaluate the effect of SOX regimen as neoadjuvant chemotherapy by detecting some microRNAs. METHODS: Total 120 GC patients who had received neoadjuvant chemotherapy (SOX regimen) were recruited with 100 healthy participants as control contemporarily. Age and gender have no significant difference in both groups (P > .05). The effect of chemotherapy was evaluated by the results of CT scan and surgery. Also, adverse effects of chemotherapy were documented. Peripheral blood of GC patients was collected twice: one day before chemotherapy and surgery, respectively, whereas healthy controls' peripheral blood was collected once. Quantitative real-time PCR (qPCR) was utilized to detect expression of miR-145, miR-185, miR-381, and miR-195 of peripheral blood in both groups. RESULTS: One hundred and twenty patients with advanced GC completed a total of 386 cycles of neoadjuvant chemotherapy with effective rate at 84.17% (101 of 120). Expression of miR-145, miR-185, and miR-381 of patients with GC was lower than that in the control group before chemotherapy commence (all P < .05), while the expressions of miR-145 and miR-185 elevated noticeably in CG patients after neoadjuvant chemotherapy (P < .05). The differences in the expression of miR-145 and miR-185 in advanced GC patients with different chemotherapy outcomes were detected. CONCLUSION: Patients with GC at advanced stages had aberrant miRs expressions. Detection of miR-145 and miR-185 expression may assist to predict effectiveness and adverse effects of SOX regimen as neoadjuvant chemotherapy.

An Energy-Balanced Clustering Protocol Based on an Improved CFSFDP Algorithm for Wireless Sensor Networks.

Clustering, as an essential part in an hierarchy protocol that can prolong the network lifetime, is influenced by the cluster head selection and clustering scheme. A new clustering algorithm called clustering by fast search and finding of density peaks (CFSFDP) based on local density and distance is implementable and efficient. In this paper, we combine this clustering algorithm with a hierarchy protocol in wireless sensor networks (WSNs). However, energy consumption in each round is unbalanced only considering these two variables during the clustering phase, which leads to the early death of the first node. In order to solve this problem, we take residual energy into consideration in our improved CFSFDP-E (energy) algorithm so as to ultimately balance the energy consumption of the network. We analyze different forms of energy and choose a dynamic threshold for each round in the CFSFDP-E algorithm. Simulation results demonstrate that the proposed approach can not only postpone the death of the first node by almost 50% compared to LEACH, but that it also outperforms several related protocols with respect to energy efficiency.

An Ebola Virus-Like Particle-Based Reporter System Enables Evaluation of Antiviral Drugs In Vivo under Non-Biosafety Level 4 Conditions.

UNLABELLED: Ebola virus (EBOV) is a highly contagious lethal pathogen. As a biosafety level 4 (BSL-4) agent, however, EBOV is restricted to costly BSL-4 laboratories for experimentation, thus significantly impeding the evaluation of EBOV vaccines and drugs. Here, we report an EBOV-like particle (EBOVLP)-based luciferase reporter system that enables the evaluation of anti-EBOV agents in vitro and in vivo outside BSL-4 facilities. Cotransfection of HEK293T cells with four plasmids encoding the proteins VP40, NP, and GP of EBOV and firefly luciferase (Fluc) resulted in the production of Fluc-containing filamentous particles that morphologically resemble authentic EBOV. The reporter EBOVLP was capable of delivering Fluc into various cultured cells in a GP-dependent manner and was recognized by a conformation-dependent anti-EBOV monoclonal antibody (MAb). Significantly, inoculation of mice with the reporter EBOVLP led to the delivery of Fluc protein into target cells and rapid generation of intense bioluminescence signals that could be blocked by the administration of EBOV neutralizing MAbs. This BSL-4-free reporter system should facilitate high-throughput screening for anti-EBOV drugs targeting viral entry and efficacy testing of candidate vaccines. IMPORTANCE: Ebola virus (EBOV) researches have been limited to costly biosafety level 4 (BSL-4) facilities due to the lack of animal models independent of BSL-4 laboratories. In this study, we reveal that a firefly luciferase-bearing EBOV-like particle (EBOVLP) with typical filamentous EBOV morphology is capable of delivering the reporter protein into murine target cells both in vitro and in vivo Moreover, we demonstrate that the reporter delivery can be inhibited both in vitro and in vivo by a known anti-EBOV protective monoclonal antibody, 13C6. Our work provides a BSL-4-free system that can facilitate the in vivo evaluation of anti-EBOV antibodies, drugs, and vaccines. The system may also be useful for mechanistic study of the viral entry process.

Upregulated Vav2 in gastric cancer tissues promotes tumor invasion and metastasis.

Several studies have proved that Vav2 gene is associated with the carcinogenesis of some tumors, but the relationship between Vav2 gene and gastric cancer remains unclear. Purpose of this study is to detect the expression of Vav2 protein in gastric cancer tissues and to evaluate the clinical value of Vav2. Furthermore, both effect of Vav2 gene on invasion and metastasis of gastric cancer cells and its mechanism are investigated in vitro. Results showed that positive rate of Vav2 protein was significantly higher in gastric cancer tissues than in adjacent tissues and notably higher in metastatic lymph nodes than in gastric cancer tissues. Results of western blot were consistent with immunohistochemistry. Expression of Vav2 protein in gastric cancer tissues was related to degree of tumor differentiation, lymph node metastasis, and clinical stages. Inhibition of endogenous Vav2 in BGC823 cells led to significantly decreased cell activity, migration, and invasion ability in vitro, and expression of Rac1, MMP-2, and MMP-9 decreased, whereas expression of TIMP-1 increased. We concluded that Vav2 might promote invasion and metastasis of gastric cancer by regulating some invasion and metastasis-related genes.

[Hypoxia-inducible factor-1α and CD133 predicts pathological complete response and survival for locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy].

Objective: To investigate the expression of hypoxia-inducible factor 1α (HIF-1α) and CD133 in predicting pathologic remission and survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy. Methods: One hundred and fourteen patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from January 2010 to December 2015 in Jinhua Municipal Central Hospital were enrolled in the study. RT-PCR and immunohistochemistry methods were used to detect the mRNA and protein expression of HIF-1α and CD133 before and after chemoradiotherapy. Spearman rank correlation was used to analyze the correlation between HIF-1α and CD133 mRNA expression. Univariate and logistic multivariate analyses were used to determine the factors related to pathological complete response (pCR). Logistic regression analysis and Cox's proportional hazard model were used to determine factors related to overall survival and recurrence-free survival. Results: The expression of HIF-1α and CD133 mRNA was correlated with pT, ypTNM, pCR, recurrence and metastasis of rectal cancer, while not correlated with sex, age and BMI of patients. HIF-1α mRNA expression was positively correlated with CD133 mRNA expression ( α=0.579, P=0.000). Immunohistochemistry analysis showed that residual cancer cells strongly expressing HIF-1α also expressed CD133 strongly. Univariate analysis showed that HIF-1α mRNA and CD133 mRNA were significantly correlated with pCR ( P=0.001, P=0.022, respectively). Multivariate analysis showed that HIF-1α and CD133 mRNA expression were independent prognostic factors of pCR ( P=0.012, P=0.047, respectively). Cox regression analysis showed that the expression of HIF-1α mRNA and CD133 mRNA were independent predictors of recurrence-free survival and overall survival ( P=0.025, P=0.033, respectively). Conclusion: The study indicates that HIF-1α and CD133 can predict pathological complete remission and survival of patients with locally advanced rectal cancer.

Single Neutralizing Monoclonal Antibodies Targeting the VP1 GH Loop of Enterovirus 71 Inhibit both Virus Attachment and Internalization during Viral Entry.

UNLABELLED: Antibodies play a critical role in immunity against enterovirus 71 (EV71). However, how EV71-specific antibodies neutralize infections remains poorly understood. Here we report the working mechanism for a group of three monoclonal antibodies (MAbs) that potently neutralize EV71. We found that these three MAbs (termed D5, H7, and C4, respectively) recognize the same conserved neutralizing epitope within the VP1 GH loop of EV71. Single MAbs in this group, exemplified by D5, could inhibit EV71 infection in cell cultures at both the pre- and postattachment stages in a cell type-independent manner. Specifically, MAb treatment resulted in the blockade of multiple steps of EV71 entry, including virus attachment, internalization, and subsequent uncoating and RNA release. Furthermore, we show that the D5 and C4 antibodies can interfere with EV71 binding to its key receptors, including heparan sulfate, SCARB2, and PSGL-1, thus providing a possible explanation for the observed multi-inhibitory function of the MAbs. Collectively, our study unravels the mechanism of neutralization by a unique group of anti-EV71 MAbs targeting the conserved VP1 GH loop. The findings should enhance our understanding of MAb-mediated immunity against enterovirus infections and accelerate the development of MAb-based anti-EV71 therapeutic drugs. IMPORTANCE: Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which has caused significant morbidities and mortalities in young children. Neither a vaccine nor an antiviral drug is available. Neutralizing antibodies are major protective components in EV71 immunity. Here, we unraveled an unusual mechanism of EV71 neutralization by a group of three neutralizing monoclonal antibodies (MAbs). All of these MAbs bound the same conserved epitope located at the VP1 GH loop of EV71. Interestingly, mechanistic studies showed that single antibodies in this MAb group could block EV71 attachment and internalization during the viral entry process and interfere with EV71 binding to heparan sulfate, SCARB2, and PSGL-1 molecules, which are key receptors involved in different steps of EV71 entry. Our findings greatly enhance the understanding of the interplays among EV71, neutralizing antibodies, and host receptors, which in turn should facilitate the development of an MAb-based anti-EV71 therapy.