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Although Convolutional Neural Networks (CNNs) have significantly improved the development of image Super-Resolution (SR) technology in recent years, the existing SR methods for SAR image with large scale factors have rarely been studied due to technical difficulty. A more efficient method is to obtain comprehensive information to guide the SAR image reconstruction. Indeed, the co-registered High-Resolution (HR) optical image has been successfully applied to enhance the quality of SAR image due to its discriminative characteristics. Inspired by this, we propose a novel Optical-Guided Super-Resolution Network (OGSRN) for SAR image with large scale factors. Specifically, our proposed OGSRN consists of two sub-nets: a SAR image Super-Resolution U-Net (SRUN) and a SAR-to-Optical Residual Translation Network (SORTN). The whole process during training includes two stages. In stage-1, the SR SAR images are reconstructed by the SRUN. And an Enhanced Residual Attention Module (ERAM), which is comprised of the Channel Attention (CA) and Spatial Attention (SA) mechanisms, is constructed to boost the representation ability of the network. In stage-2, the output of the stage-1 and its corresponding HR SAR images are translated to optical images by the SORTN, respectively. And then the differences between SR images and HR images are computed in the optical space to obtain feedback information that can reduce the space of possible SR solution. After that, we can use the optimized SRUN to directly produce HR SAR image from Low-Resolution (LR) SAR image in the testing phase. The experimental results show that under the guidance of optical image, our OGSRN can achieve excellent performance in both quantitative assessment metrics and visual quality.

Background/Aim: Long noncoding RNA TARID (lncRNA TARID) can activate the tumor suppressor TCF21 in tumorigenesis by inducing promoter demethylation. However, the impact on lncRNA TARID and its variants of coronary artery disease (CAD) are poorly understood. Methods We performed a case-control study enrolling 949 case patients and 892 controls to assess genotype. Five variants were genotyped by TaqMan assay. 20 case patients and 20 controls were used to evaluate the expression of lncRNA TARID. The qRT-PCR and cell cycle analysis were applied to examined cell proliferation and cell distribution. Results This study indicated that rs2327433 GG genotype was associated with CAD risk adjusting for traditional risk factors (OR=2.74, 95%CI: 1.10-6.83, P=0.03). Our results analyses revealed that the genotype of rs2327433 was related to the proportion of CAD patients with left anterior descending artery disease and left circumflex artery disease (P=0.025 and P=0.025, respectively). The results showed that the minor allele frequency of rs2327433 was significantly correlated with the severity of the disease (P=0.029). The eQTL analysis showed that rs2327433 may affect the transcription factors TCF21 regulated by lncRNA TARID. We found that TARID silencing regulated the cell proliferation and altered cell cycle progression by induced upregulation of CDK1 and PCNA. Conclusions SNP rs2327433 in lncRNA TARID was associated with CAD risk and the severity of CAD in Chinese Han population. Furthermore, SNP rs2327433 may affect the expression of atherosclerosis-related transcription factor TCF21 regulated by lncRNA TARID. Finally, our study provided a new lncRNA-dictated regulatory mechanism participating in cell proliferation.

This study explores how two dimensions of employees’ knowledge-hiding behaviours, explicit knowledge hiding and tacit knowledge hiding, influence a firm’s innovation quality. Furthermore, knowledge flow within the firm is examined as a moderator in these relationships. We tested corresponding hypotheses based on a research sample of 791 respondents across different industries and regions of China. Empirical results reveal that both explicit and tacit knowledge-hiding behaviours have inverted U-shaped relationships with innovation quality, and knowledge flow within the firm positively moderates these curvilinear relationships. The theoretical contributions of the study are to provide a more advanced understanding of the link between knowledge-hiding behaviours and innovation quality, as well as the role of knowledge flow within the firm. It is therefore suggested that practitioners encourage effective knowledge flow that helps to reduce individual employees’ intentions of knowledge hiding and strengthen their innovation capability, which in turn promotes a firm’s innovation quality.

OBJECTIVE: MiRNAs are important regulators of inflammation and wound healing. However, the mechanisms through which miRNAs regulate wound healing under normal and diabetic conditions are poorly understood. We aimed to determine the effects of miR-146a on the pathogenesis of wound healing in normal and streptozotocin (STZ)-induced diabetic mice. APPROACH: Wild-type (WT) and miR-146a knockout (KO) mice were induced to develop diabetes with STZ. Next, skin and corneal wounds were produced and measured. Percent wound closure and histology were evaluated. Inflammation at wound sites was analyzed using flow cytometry, reverse-transcription PCR, and western blot. RESULTS: Healing of wounded skin was significantly delayed in miR-146a KO compared with WT mice. However, corneal epithelial wound healing did not differ significantly in the mice with normal blood glucose, whereas corneal and skin wound healing was significantly delayed in KO mice with diabetes. Neutrophil infiltration increased in skin wounds of KO compared with normal mice. The potential mechanisms were associated with dysregulated interleukin 1β, tumor necrosis factor alpha (TNF-α), IRAK1 (interleukin-1 receptor-associated kinase 1), TRAF6 (TNF receptor-associated factor 6), and nuclear factor kappa B (NF-κB) signaling induced by miR-146a KO. INNOVATION: Skin wound healing was delayed in miR-146a KO mice and enhanced inflammatory responses were mediated by the NF-κB signaling pathway. CONCLUSIONS: Deficiency in miR-146a delayed skin wound healing by enhancing inflammatory responses in normal and diabetic mice. Therefore, miR-146a may be a potential target for modulation to accelerate skin wound healing.

In this paper, a new type of Vivaldi antenna with heat dissipation enhancement is proposed and manufactured based on three-dimensional (3-D) printing and printed circuit board (PCB) technologies. A longitudinal slot on substrate integrated waveguide (SIW) is employed to feed Vivaldi radiation structure, which replaces the balun structure of traditional Vivaldi antennas. The measured 10-dB bandwidth of antenna element reaches up to 34.48% (21.77-30.39 GHz) and the in-band realized boresight gain is 6.5-8.8 dBi. The 1×4 Vivaldi antenna array with 28.72% (21.63-28.81 GHz) bandwidth and a gain range of 10.5-12.5 dBi is achieved. The fin-shaped structure of the antenna array further enhances the heat dissipation while increasing the gain up to the range of 13.4-15.5 dBi. The measured results are in good agreement with the simulated ones. The proposed antenna array has important application potential in 5G millimeter-wave systems.

PurposeThis paper aims to identify the key antecedences contributing consumer similarity perception toward store branded lookalikes (SBLs), testing to what extent each of the antecedences influences the overall similarity perception.Design/methodology/approachTwo empirical studies were conducted. Study 1 was an online experiment to test the relative importance of packaging features on similarity judgment of SBLs. Study 2 examined the impacts of consumer characteristics and store related elements on similarity perception through a Qualtrics web-based questionnaire covering seven product categories.FindingsThis research yields two key findings. First of all, it revealed that all three packaging attributes studied (i.e. size and shape, image and color) exert positive influence on similarity judgment of SBLs, among which color shows the most significant importance, followed by size and shape, and then color. Then, it showed that brand loyalty fully mediated the effect of brand familiarity on consumers' similarity perception, giving that no direct effect was found from brand familiarity to similarity perception but consumers' brand loyalty increased as they become more familiar with the NBs. As consumers become more loyal to the brands, they would perceive the SBLs to be less similar to imitated national brands.Practical implicationsThis research confirmed the significance of proper manipulation of packaging design, either to the SBLs or to the imitated NBs. It also reveals the critical role of gaining high familiarity and strong loyalty for the NB manufacturers. For retailers, the research highlights the need to maintain a better store image in order to take advantage of SBLs to help with marketing competition.Originality/valueThis research contributes new knowledge on the lookalike phenomenon by uncovering the prerequisites that cause similarity perception between two products.

Assessing activity intensity has its clinical importance to the treatment of diseases such as obesity. The metabolic equivalent of task (MET) is the objective numerical measure for assessing the intensity of general activities. Because daily activities vary, an activity cannot be easily mapped to a MET value, which makes intensity quantification of daily activities more challenging than monotonous activities. In this article, we use the data from wearable inertial measurement unit (IMU) sensors and a calorimetry machine to map the relationship between activity motions and intensities. In detail, we describe an end-to-end approach for predicting METs of preschoolers. Based on the collection of data from the two devices, we present a systematic approach to address the aforementioned challenges and to predict physical activity intensity of preschoolers. Specifically, a dynamic synchronization method is first proposed to deal with the displaced data series, which takes the dynamic time warping (DTW) as an evaluation criterion. Second, additional features are designed to reinforce the ability of intensity prediction. Third, proposed methods are tested on a two-layer bidirectional long short term memory (LSTM) network model to predict MET values. Our experimental results reveal the effectiveness of the end-to-end approach.

Accidents in chemical production usually result in fatal injuries, economic losses, and negative social impacts. To ensure personnel security in such cases, previous research has often used digital data, such as physical signals. However, the valuable textual information contained in chemical security texts, such as expert knowledge, has not yet been explored. Therefore, there is an increasing demand to mine useful information from these unstructured data. In this study, natural language processing (NLP) was applied to the hazard and operability (HAZOP) analysis reports. The classification model was trained to learn the classification of consequence severity levels in high-quality HAZOP analysis reports, which will not only ensure the consistency of the analysis results, but also help smaller chemical plants perform security analysis. In the classification model, we introduced Bidirectional Encoder Representation from Transformers (BERT), which, for word embedding, which is a powerful NLP pre-training model and significantly improved the effectiveness of the model. Through these application scenarios, the feasibility and possibility of applying NLP in chemical security text have been confirmed to a certain extent. In addition to digital data, future security managers will be able to monitor chemical production using natural language.

Chemical processes usually exhibit complex, high-dimensional, time-varying, and non-Gaussian characteristics, and the diagnosis of faults in chemical processes is particularly important. However, many current fault diagnosis methods do not consider the temporal correlation of process data, feature selection, and feature sequence arrangement. To solve this problem, this paper presents a fault diagnosis method using a dynamic convolutional neural network, based on a genetic algorithm (GA), for optimizing a feature sequence. First, the input data are transformed into a two-dimensional matrix by adding the dimension of time characteristics. Second, the GA is used to select the features, and the sequence of the selected features is optimized. Finally, the optimized feature sequence is input into the convolutional neural network (CNN) to obtain the final diagnosis results. The Tennessee Eastman chemical process is used for experimental analysis, and the proposed model is compared with the weighted cascade forest, deep belief network (DBN), optimized DBN, long short-term memory + CNN and feature selection using random forest models. The experimental results show that the proposed model has higher diagnostic accuracy. The average diagnosis rate of 20 faults is found to be 89.72%.

BACKGROUND Because of their cancer and treatment adverse effects, most pediatric oncology patients will experience 1 or more symptoms at one time that can seriously affect their quality of life. Because these children are attached to parents, their symptom burden directly influences the parental stress level and parental interpretations of their children's quality of life. OBJECTIVE The aim of this study was to examine the association between child-reported symptom burden and the pediatric quality of life reported by children with cancer and their parents, and whether parental perceived stress mediates these relationships. METHODS In a cross-sectional design, convenience sampling was used to recruit 80 parent-child dyads. Advanced statistical methods were adopted to analyze the mediating effects of parental stress between children's symptom burden and their quality of life. RESULTS The results revealed that parental stress was the mediator in the relationship between child-reported symptom burden and children's quality of life reported by parents. The results also showed that parental stress was not a mediator in the relationship between child-reported symptom burden and their quality of life. This underscored the differences in interpretations of quality of life reported by children and their parents. CONCLUSION Children's symptom burden is an important factor in predicting parental stress level and the quality of life reported by the children. Children's voice should be incorporated whenever possible. IMPLICATIONS FOR PRACTICE The knowledge gained from this study will facilitate intervention development to enhance parents' abilities in stress management and symptom management for their children with the support of the nursing profession.

Background Some pain, fatigue, and gastrointestinal adverse events were observed in potential association with injection of COVID-19 vaccines, while there was no preventive intervention for it. We aim to investigate the efficacy of auricular acupressure (AA) therapy in preventing and relieving AEFI after injection of COVID-19 vaccine. Methods The study design is a randomized, multicentre, three-arm controlled, single-blind trial. Participants meeting the inclusion criteria will be advertised and enrolled and assigned in the medical institutions randomly for post-injection observation. No less than 360 participants will be randomized into one of three groups: auricular acupressure group, sham auricular acupressure group, and wait-list group. Interventions will be performed immediately and will happen 4 to 5 times per day for 5 days. The primary clinical outcomes will be quality and quantity evaluation among participants who reported any AEFI and who reported local pain at injection site. Secondary outcomes will concern headache, muscle and (or) joint pain, fatigue, nausea, vomiting, diarrhoea, and other potential events. All the outcomes will be assessed at baseline and 1, 3, 5, 7, and 14 days after the injection. Both intention-to-treat and per-protocol analyses will be performed, with significance level determined as 5%. Discussion Results of this trial will help to clarify the value of auricular acupressure therapy in preventing and relieving overall and certain adverse events following immunization after injection of COVID-19 vaccine. Trial registration China Clinical Trial Registry (ChiCTR) (ChiCTR2100043210). Registered on 8 February, 2021.

Identification of cancer-predisposing germline variants in childhood cancer patients is important for therapeutic decisions, disease surveillance and risk assessment for patients, and potentially, also for family members. We investigated the spectrum and prevalence of pathogenic germline variants in selected childhood cancer patients with features suggestive of genetic predisposition to cancer. Germline DNA was subjected to exome sequencing to filter variants in 1048 genes of interest including 176 known cancer predisposition genes (CPGs). An enrichment burden analysis compared rare deleterious germline CPG variants in the patient cohort with those in a healthy aged control population. A subset of predicted deleterious variants in novel candidate CPGs was investigated further by examining matched tumor samples, and the functional impact of AXIN1 variants was analyzed in cultured cells. Twenty-two pathogenic/likely pathogenic (P/LP) germline variants detected in 13 CPGs were identified in 19 of 76 patients (25.0%). Unclear association with the diagnosed cancer types was observed in 11 of 19 patients carrying P/LP CPG variants. The burden of rare deleterious germline variants in autosomal dominant CPGs was significantly higher in study patients versus healthy aged controls. A novel AXIN1 frameshift variant (Ser321fs) may impact the regulation of β-catenin levels. Selection of childhood cancer patients for germline testing based on features suggestive of an underlying genetic predisposition could help to identify carriers of clinically relevant germline CPG variants, and streamline the integration of germline genomic testing in the pediatric oncology clinic.

This study aimed to explore the health-related quality of life (HRQoL) and associated variables in children with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitors (TKIs). A cross-sectional questionnaire was given to children with CML and their parents, who were

The incidence of posterior pilon variant fractures has been underestimated. The purpose was to study the characteristics of posteromedial (PM) and posterolateral (PL) fragments in CT imaging of posterior pilon variant fractures, and to provide help for clinical diagnosis and treatment. CT imaging data of 109 cases of posterior pilon variant fractures in our hospital from January 2013 to December 2020 were retrospectively analyzed. According to Mason and Molloy classification, PM fragments were further divided into pilon subtypes and avulsed subtypes. The largest actual area of fragments in axial and sagittal were selected as the study plane, and the maximum axial lengths of X, Y and Z, α angle, β angle, fragment area (S1–7) and fragment area ratio (FAR1-4), interfragmentary (IF) angle, and back of tibia (BT) angle were measured. A total of 109 cases were included in this study, 61 of whom were pilon subtypes [90.16% were supination-external rotation (SER) injuries]. 48 cases were avulsed subtypes [81.25% were pronation-external rotation (PER) injuries]. Pilon subtypes were larger than avulsed subtypes in X, Y, Z, α2 Angle, β2 Angle, fragment area and ratio, and IF and BT angle (P 0.05). The morphology of pilon subtype was larger than that of avulsion subtype. According to fragment size, morphology, and injury mechanism, two fragments of pilon subtype should be anatomic reduction and fixation. However, the PL fragment of avulsion subtype should to be fixed, while PM fragment may only need conservative treatment.

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease threatening the health of the elderly, but the available therapeutic and preventive drugs remain suboptimal. Loganin, an iridoid glycoside extracted from Cornus officinalis, is reported to have anti-inflammatory and memory-enhancing properties. This study is aimed to explore the influence of loganin on cognitive function in 3xTg-AD mice and the underlying mechanism associated with its neuroprotection. According to the results of behavioral tests, we found that administration of loganin could significantly alleviate anxiety behavior and improve memory deficits of 3xTg-AD mice. Furthermore, immunohistochemical analysis displayed that there were decreased Aβ deposition in the hippocampus and cortex of 3xTg-AD mice treated with loganin compared with the control mice. Importantly, the Aβ-related pathological change was mainly involved in altering APP expression and processing. And loganin was also found to reduce the levels of phosphorylated tau (i.e. pTauS396 and pTauS262) in 3xTg-AD mice. By performing 2D-DIGE combined with MALDI-TOF-MS/MS, we revealed 28 differentially expressed proteins in the 3xTg-AD mice treated with loganin compared with the control mice. Notably, 10 proteins largely involved in energy metabolism, synaptic proteins, inflammatory response, and ATP binding were simultaneously detected in 3xTg-AD mice compared to WT mice. The abnormal changes of energy metabolism (PAGM1 and ENO1), synaptic proteins (SYN2 and Cplx2), inflammatory response (1433Z) were verified by western blot. Overall, our study suggested that loganin could be used as a feasible candidate drug to ameliorate molecular deficits, pathologies and cognitive impairment for prevention and treatment of AD.

To improve the punching shear capacity and ductility of slab-column connections, a new type of slab-column connection embedded with a steel skeleton was proposed and studied. An experimental investigation was conducted by testing a total of nine simply supported slab-column connection specimens subjected to vertical loads. The influences of the type of the steel skeleton, reinforcement ratio, steel content and slab thickness on the punching shear behavior of the composite connections were investigated. The test results indicated that the embedded steel skeleton could effectively improve the punching shear capacity of the slab-column connections, and the structural ductility was increased by changing the failure mode from punching shear to bending-punching. In addition, finite element (FE) software was employed to conduct parametric studies. Simulation results showed that the effects of the reinforcement ratio and the length of I-shaped steel on punching shear behavior of the composite slab-column connections were proved to be significant. Based on experimental and numerical studies, an analytical model was developed to predict the punching shear capacity of the proposed composite connections, and the calculated values were well in agreement with the results of tests and simulations.

PurposeFinance is crucial to boosting agricultural development in developing countries. This paper aims to investigate the effects of rural formal and informal financial access on agricultural technical efficiency (TE) in China.Design/methodology/approachBased on the survey data of demonstrative family farms in Langxi county, Anhui province and Wuhan city, Hubei province in central China in 2017, this research assesses agricultural TE by using a three-stage DEA model. It adopts the tobit model to evaluate the effects of formal and informal financial access on TE, and to explore the heterogeneous effects by types, management states and scales. It uses the OLS regression and PSM method to check the robustness, and applies the IV-Tobit method to solve the endogeneity. The authors apply the mediation effect model to explore the channels through which financial access impacts TE.FindingsFamily farms' average TE reaches 13.9%, which shows much room for improvement under the given technical conditions and constant inputs. The research confirms the advantage of formal financial access in raising TE relative to informal financial access. The heterogeneous analysis documents more prominent effects of formal financial access on enhancing TE of aquaculture, hybrid, demonstration and large farms. The mediating effect model reveals that the enhancing TE effect of formal financial access derives from improved machinery investment and family labor division rather than land circulation.Originality/valueThe research clarifies finance into formal and informal finance. The results have considerable policy implications for rural financial policies in China.

In this work, the closing process of aerial self-locking nuts with different materials was simulated using static analysis in Abaqus/Standard. The effects of different closing amounts of self-locking nuts with different types on the locking performance of self-locking nuts were investigated. In order to analyze the locking performance of self-locking nuts, the method was measured by using the maximum equivalent stress on the root of the third thread. Finally, the equivalent stress range of self-locking nuts of different materials and the closing size range of self-locking nuts of different types were obtained. The equivalent stress ranges of TC4, GH2132 and GH4169 self-locking nuts were 1060–1090 MPa, 664–712 MPa and 860–920 MPa, respectively. At the same time, the corresponding closing amount of M5-M10 self-locking nuts is 0.22–0.46 mm, 0.37–0.64 mm and 0.43–0.75 mm, respectively. (The simulation results show that the equivalent stress of different types of self-locking nuts with the same material shows the characteristics of layered distribution. The equivalent stress of the same type of self-locking nut increases with the increase of the closing amount. When the closing amount is the same, the smaller the type of the nut, the greater the equivalent stress. For the same of the equivalent stress, the closing amount increases with the increase of the type of self-locking nuts.) The conclusions can provide a reasonable theoretical reference for the closing process of aerial self-locking nuts with different materials.

Background Patients undergoing cardiac operation are susceptible to anemia. Low hemoglobin concentration is a risk factor for composite adverse events and death after cardiac operation. Here we investigated the association of postoperative nadir hemoglobin with adverse outcomes in patients undergoing on-pump cardiac operation. Methods Adult patients in 2 medical centers were retrospectively analyzed. The primary outcome was postoperative composite adverse events. The secondary outcome was all-cause death in the hospital. Results Of the 8206 patients analyzed, 1628 (19.8%) experienced composite adverse events after operation and 109 (1.3%) died. Patients receiving on-pump cardiac operation with nadir hemoglobin of 9.0 to 9.9 g/L showed a low incidence of composite adverse events (175 of 1423 [12.3%]) and death (5 of 1423 [0.4%]). Compared with nadir hemoglobin at 9.0 to 9.9 g/dL, the relative risk (RR) of composite adverse events increased stepwise as nadir hemoglobin fell below 9.0 g/dL: adjusted RR was 1.44 (95% confidence interval [CI], 1.14-1.83) for 8.5 to 8.9 g/dL, 1.56 (95% CI, 1.23-1.99) for 8.0 to 8.4 g/dL, 1.66 (95% CI, 1.31-2.11) for 7.5 to 7.9 g/dL, 2.22 (95% CI, 1.75-2.83) for 7.0 to 7.4 g/dL, and 4.00 (95% CI, 3.18-5.04) for less than 7 .0 g/dL. Furthermore, the risk of death was significantly higher when nadir hemoglobin was below 7.0 g/dL than when it was 9.0 to 9.9 g/dL (RR, 5.36; 95% CI, 2.20-16.12). Conclusions Compared with the risks when nadir hemoglobin is 9.0 to 9.9 g/dL, the risk of composite adverse events increases when postoperative nadir hemoglobin is below 9.0 g/dL, whereas risk of death increases when nadir hemoglobin is below 7.0 g/dL.

AIM This study aims to explore the risk factors leading to poor wound healing after forceps delivery. METHOD In this retrospective study, 74 patients undergoing forceps delivery with poor wound healing were compared with contemporary randomly selected 74 patients undergoing forceps delivery but with normal wound healing. RESULTS Compared to the normal healing group, the poor healing group had larger birthweight (p = 0.01), longer labor length (805.9 ± 356.4 min vs. 572.9 ± 306.3 min, p

BACKGROUND Moebius syndrome (MBS) is a nonprogressive and rare congenital neuromuscular disorder involving the facial nerve and abductor nerve; it mainly manifests as facial paralysis and eye strabismus paralytic symptoms. Tissues in the oral cavity are also compromised, characterized by microstomia, micrognathia, tongue malformation, cleft lip, high arched palate or cleft palate, bifid uvula, and dental malocclusion. Therefore, dentistry plays a fundamental and crucial role in caring for these individuals. However, there is limited available data on MBS treatment, particularly regarding dental management. CASE SUMMARY This case report presents dental treatment of a 21-year-old man with MBS and discusses crucial interactions among oral complications of MBS. In this case, the patient was clinically characterized by congenital neuromuscular disorder, occlusal disorders, and tooth and gum problems. It is noteworthy that the patient presented early eruption of deciduous teeth 2 mo after birth, which has not been reported in other MBS cases and suggests a potentially new clinical manifestation of this syndrome. It is important to note that MBS cannot be cured, and oral manifestations of this syndrome can be managed by a multidisciplinary health care team that helps the patient maintain oral hygiene and dental health. After a series of oral treatments, no obvious poor oral hygiene, swollen gums, or abnormal imaging results were observed after 2 years of follow-up. CONCLUSION This case addressed the oral clinical manifestations of MBS and difficulties experienced during dental management, and suggested early tooth eruption as a potentially new clinical manifestation of this syndrome. Knowledge of the loop-mediated association among oral complications of this syndrome is essential to perfecting treatments.

Introduction Patients on maintenance hemodialysis (MHD) are highly predisposed to low bone mineral density (BMD). This study aims to assess the value of quantitative ultrasound (QUS), bioelectrical impedance analysis (BIA), and their combination in detecting high-risk patients for low BMD in MHD. Methods Patients’ BMD of the total hip, femoral neck, and lumbar spine were measured using dual-energy X-ray absorptiometry (DXA). Bone mineral content (BMC) was assessed using BIA. Calcaneal BMD was measured using QUS. Patients with a T-score of ≤-2.5 were recorded as ‘low BMD.’ Results Overall, 93 subjects (62.37% female; mean age, 60.8 ± 16.2 years) were included in this cross-sectional study; approximately 36.56% met the ‘low BMD’ criteria. QUS-T score predicted low BMD with an area under the curve (AUC) value of 0.738, sensitivity of 70.59%, and specificity of 76.27%. The AUC for low BMD diagnosis using the BMC index (BMCI) measured through BIA was 0.679 (sensitivity, 91.18%; specificity, 38.98%). On the other hand, the combination of QUS-T score and BMCI yielded a higher AUC value of 0.762 with an improved specificity of 88.14%. Compared with the QUS and BIA alone, the net reclassification improvement (NRI) of the combination model increased by 47.16% (p = 0.022) and 78.36% (p

Background Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode. Methods Flow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients. Results The in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events. Conclusion In sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.

BACKGROUND: A meta-analysis was conducted to evaluate the curative effect of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC). METHODS: Chinese and English databases were searched using free combinations of the terms “bladder cancer,” “radical cystectomy,” “muscle invasive bladder cancer,” and “bladder preservation.” Review Manager 5.3 software was used for the meta-analysis. RESULTS: A total of 12 articles were included in the meta-analysis, most of which had low-bias risk and were of medium and high quality. A funnel chart showed that the circles of some studies were basically symmetrical with the midline, suggesting that the research accuracy was high, the publications were not biased, and the final conclusions were credible. Twelve articles analyzed patients’ 5-year survival rate in randomized controlled trials (RCTs). In these RCTs, the experimental group (expt group) comprised 775 cases and the control group (ctrl group) comprised 766 cases. A heterogeneity test using the fixed-effects model (FEM) showed Chi(2) =2.19, df =11, I(2)=0%, P=1.00>0.1, Z =2.57, odds ratio (OR) =1.30, 95% confidence interval (CI): 1.06–1.59, and P=0.010.1, Z =1.42, OR =1.32, 95% CI: 0.90–1.94, and P=0.16>0.05. 6 articles analyzed 5-year distant metastasis rates (DMRs) in RCTs. The overall heterogeneity test showed Chi(2) =1.68, df =5, I(2)=0%, P=0.89>0.1, Z =1.70, OR =1.28, 95% CI: 0.96–1.71, and P=0.09>0.05). DISCUSSION: Our meta-analysis confirmed that radical cystectomy is effective in the treatment of MIBC and is worthy of clinical promotion.

With the development of transmission and distribution price reform in China, pumped storage power station can not continue to be included in the effective assets of the power grid, and its cost can not be dredged through the transmission and distribution price, so it is urgent to find a way to protect its own income through the market. This paper innovatively proposes a “three-stage” competitive optimization model for pumped-storage power stations, using a quadratic programming algorithm with two consecutive iterations to convert the discrete programming problem into a linear convex programming problem, reducing the difficulty of calculation and improving the calculation accuracy. Finally, the reinforcement learning algorithm is used to obtain the real-time bidding strategy of the pumped storage power station, and continuous feedback is provided. The calculation example analysis shows that compared with the traditional model, the “three-stage” model can bring better benefits to the pumped storage power station, and when the actual value of demand fluctuates within −8%, the pumped storage power station has the ability to resist risks higher than the market average. And when the proportion of renewable energy increases from the current 8%–30%, the revenue of pumped storage power plants will drop by 20%.

Presently, the Internet of Things (IoT) and big data analytics technology offer enormous opportunities to disaster risk management services. Recent disaster risk management patterns involve disaster risk reduction to avoid future disaster risks, minimize current disastrous risks, resilience building, and disaster loss reduction. The main challenges in disaster management are communication within a disaster zone which is being disrupted. In this paper, the Internet of Things assisted disaster risk management framework (IOTDRMF) has been proposed for technical resources to communicate the emergency time and better visibility into reliable and prompt decision-making through observing, evaluating, and forecasting natural disasters. This IOTDRMF utilizes big data analytics to analyze disaster risk management build a kind of spatial data communication network infrastructure, making it a priority to establish rules, protocols, and knowledge sharing. The experimental results show the IOTDRMF, and big data analytics compensate for a weak communication network infrastructure and better decision-making to handle disaster risk management.

Background Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli–caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables. Methods A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor. Results Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk ( 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer–Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P Conclusions Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality.

Selumetinib (ARRY-142886), an oral, potent and highly selective allosteric mitogen-activated protein kinase kinase 1/2 inhibitor, is approved by the US Food and Drug Administration for the treatment of pediatric patients aged ≥2 years with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. A physiologically based pharmacokinetic (PBPK) model was constructed to predict plasma concentration-time profiles of selumetinib, and to evaluate the impact of coadministering moderate cytochrome P450 (CYP) 3A4/2C19 inhibitors/inducers. The model was also used to extrapolate pharmacokinetic exposures from older children with different body surface area to guide dosing in younger children. This model was built based on physiochemical data and clinical in vivo drug-drug interaction (DDI) studies with itraconazole and fluconazole, and verified against data from an in vivo rifampicin DDI study and an absolute bioavailability study. The pediatric model was updated by changing system-specific input parameters using the Simcyp pediatric module. The model captured the observed selumetinib pharmacokinetic profiles and the interactions with CYP inhibitors/inducers. The predictions from the PBPK model showed a DDI effect of 30% to 40% increase or decrease in selumetinib exposure when coadministered with moderate CYP inhibitors or inducers, respectively, which was used to inform dose management and adjustments. The pediatric PBPK model was applied to simulate exposures in specific body surface area brackets that matched those achieved with a 25 mg/m2 dose in SPRINT clinical trials. The pediatric PBPK model was used to guide the dose for younger patients in a planned pediatric clinical study.

Based on its excellent visible light absorption and photoelectric response capabilities, SbSI has attracted significant research attention for a wide range of applications. Despite the fact that interesting physical properties can be induced from the sophisticated band structures of SbSI, that is, either with direct or indirect band gaps, its nonlinear optical (NLO) properties are not yet fully explored. In the present work, the NLO response of SbSI nanorods is investigated by the combination of open-aperture (OA) Z-scan, pump–probe, and spatial self-phase modulation (SSPM). It is found that the synthesized SbSI nanorods possess a relatively large nonlinear absorption coefficient and a small saturable optical intensity at a wavelength of 400 nm, compared to those of other materials. More importantly, the OA Z-scan experiments suggest that the direct band gap of SbSI plays a dominant role on the NLO effects, which is further verified by the SSPM experiments. The present work suggests that the SbSI nanorods may have great potentials for optical switches and saturable absorbers.

Purpose: Ongoing clinical trials show limited efficacy for Chimeric antigen receptor (CAR) T treatment for acute myeloid leukemia (AML). The aim of this study was to identify potential causes of the reported limited efficacy from CAR-T therapies against AML. Experimental Design: We generated CAR-T cells targeting Epithelial cell adhesion molecule (EpCAM) and evaluated their killing activity against AML cells. We examined the impacts of modulating mTORC1 and mTORC2 signaling in CAR-T cells in terms of CXCR4 levels. We examined the effects of a rapamycin pretreatment of EpCAM CAR-T cells (during ex vivo expansion) and assessed the in vivo antitumor efficacy of rapamycin-pretreated EpCAM CAR-T cells (including CXCR4 knockdown cells) and CD33 CAR-T cells in leukemia xenograft mouse models. Results: EpCAM CAR-T exhibited killing activity against AML cells but failed to eliminate AML cells in bone marrow. Subsequent investigations revealed that aberrantly activated mTORC1 signaling in CAR-T cells results in decreased bone marrow infiltration and decreased the levels of the rapamycin target CXCR4. Attenuating mTORC1 activity with the rapamycin pretreatment increased the capacity of CAR-T cells to infiltrate bone marrow and enhanced the extent of bone marrow AML cell elimination in leukemia xenograft mouse models. CXCR4 knockdown experiments showed that CXCR4 contributes to the enhanced bone marrow infiltration capacity of EpCAM CAR-T cells and the observed reduction in bone marrow AML cells. Conclusions: Our study reveals a potential cause for the limited efficacy of CAR-T reported from current AML clinical trials and illustrates an easy-to-implement pretreatment strategy, which enhances the anti-AML efficacy of CAR-T cells. See related commentary by Maiti and Daver, p. 5739

BackgroundBiochemical recurrence is defined as only rising CA-125 but no radiographic evidence of disease; noteworthily, it generally precedes the onset of clinical evidence. Now treatment strategies of biochemical recurrence ovarian cancer (OC) remain controversial. Apatinib as monotherapy or in combination with other chemotherapeutic agents has shown its effect in the treatment of some advanced malignancies. In our study, we focused on the efficacy of apatinib in recurrent OC, especially its clinical activity in biochemical-only recurrent OC patients.MethodsWe retrospectively analyzed clinical material of 41 recurrent patients who had received apatinib monotherapy or apatinib plus chemotherapy between June 2016 and August 2018. Apatinib was administered at a 500mg daily dose. Response was determined according to measurable disease or serum carbohydrate antigen (CA)-125 levels. Progression-free survival (PFS) was estimated by Kaplan–Meier method.ResultsAll patients were evaluable, 19 (46.34%) had biochemical relapse and 22 (53.66%) had clinical relapse. The objective response rate (ORR) and disease control rate (DCR) in the overall population were 31.71% and 78.05%, respectively. The median PFS was 7 months (95% confidence interval 5.43–8.57). And in patients with biochemical-only relapse, the median PFS was 6 months, with ORR of 26.32% and DCR of 89.47%.ConclusionsApatinib is a well-tolerated and effective agent to delay clinical progression of patients with biochemical-only recurrent OC. More important, our study shows the promising prospect for treating OC patients with asymptomatic biochemical relapse.

Background Previous clinical trials have demonstrated that entinostat in combination with exemestane had good tolerability and significant clinical efficacy in patients with advanced hormone receptor positive (HR+) and HER2 negative (HER2−) metastatic breast cancer (MBC) in the USA. However, no clinical trials have been conducted in Chinese populations. Objective To investigate the safety, pharmacokinetics, and pilot efficacy of entinostat with or without exemestane in Chinese postmenopausal patients with locally advanced or metastatic HR+ /HER2− MBC. Patients and methods Nineteen patients received entinostat for 4 weeks (dose-limiting toxicity (DLT) observation stage) at 3, 5, or 7 mg/week, with a “3+3” dose-escalation design and in combination with exemestane thereafter (extended treatment stage: entinostat, 3 or 5 mg/week; exemestane, 25 mg/day). An additional 21 patients were enrolled to assess the entinostat (5 mg) plus exemestane (25 mg) pharmacokinetic profile and potential efficacy. Results The peak entinostat serum concentration and area under the curve increased dose proportionally, without significant interaction between entinostat and exemestane. Entinostat was well tolerated at all doses. The most common grade 3/4 adverse effects (AEs) included neutropenia (31.6%) and thrombocytopenia (15.8%). In the DLT observation stage, grade 3/4 AEs accounted for 16.7% in the 5 mg group with one suspicious DLT (G3 ventricular tachycardia) and 33.3% in the 7 mg group. In the extended treatment stage, 2/16 patients achieved partial response and three patients experienced stable disease (> 12 weeks). The median progression-free survival was 9.41 months for the additional 21 patients, who experienced grade 3/4 AEs of neutropenia (38%), thrombocytopenia (9.5%), anemia (9.5%), and fatigue (9.5%). Conclusion Entinostat with exemestane showed reasonable safety, tolerability, and encouraging efficacy in Chinese patients with HR+/HER2− MBC. These results support further evaluation in a randomized, double-blind Phase III study with a weekly 5 mg entinostat dose in a Chinese population. Trial Registration NCT02833155.

A man in his 60s with hypertension and tobacco use presented to the outpatient clinic with 3-month progressive exertional dyspnoea. ECG showed sinus rhythm with poor R-wave progression in the precordial leads. Transthoracic echocardiography (TTE) revealed normal left ventricular (LV) size and function. Coronary angiography showed no significant stenosis. However, left ventriculography found a narrow neck, thin-walled outpouching at the apex with synchronous contraction (figure 1A, B and video 1). Subsequently, MRI confirmed a small LV outpouching on the apex measuring 17×12 mm, which contained myocardium (figure 1C, D and video 2). On late gadolinium enhancement images, the entire LV myocardium was nulled without evidence of scar. During the period of follow-up, the size and location of his LV outpouching remained unchanged over time. Open in a separate window Figure 1 Ventriculogram (right anterior oblique projection) showing the contrast-filled outpouching at the apex during systole (A) and diastole (B). MRI (long axial plane of the left ventricular view) showing a small outpouching on the apex during systole (C) and diastole (D).

To explore the differences in the clinical features, treatment responses, and outcomes among children, adolescents, and adults with chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib as first-line therapy. Data from children (0–8 years for girls and 0–10 years for boys), adolescents (9–19 years for girls and 11–19 years for boys), and adults (age ≥ 20 years) with newly diagnosed CML-CP receiving imatinib as first-line therapy between 2006 and 2019 were retrospectively reviewed. In total, 135 children (cohort 1), 189 adolescents (cohort 2), and 658 adults (cohort 3: age 20–39 years, n = 305; cohort 4: age 40–59 years, n = 270; and cohort 5: age 60–83 years, n = 83) were included in this study. When compared with children, adolescents showed a significantly higher white blood cell count (P = 0.033) and basophil percentage in peripheral blood (P = 0.002) and a significantly higher prevalence of splenomegaly (P = 0.004). Both children and adolescents presented with more aggressive clinical features than adults. During median follow-ups of 28 months (range, 3–161 months) in children, 33 months (range, 3–152 months) in adolescents, and 48 months (range, 3–157 months) in adults, multivariate analysis showed that children and adolescents had higher probabilities of achieving complete cytogenetic response, major molecular response, and molecular response4.5. Notably, compared with not only adults (cohort 3 vs. cohort 1: HR = 2.03 [1.03, 3.98], P = 0.040; cohort 4 vs. cohort 1: HR = 2.15 [1.07, 4.33], P = 0.033; cohort 5 vs. cohort 1: HR = 4.22 [1.94, 9.15], P

In terms of the traditional dynamic vibration absorber (DVA), the vibration damping effect improves with the mass ratio of DVA increasing, and the vibration level of target system is effectively controlled in the case that the mass ratio of DVA is large. This characteristic restricts the application of DVA to the track because of the limited available space. This study proposes one type of DVA with negative stiffness (NSDVA) applied to floating slab track to reduce the track vibration under the condition of small mass ratio and presents a design methodology of NSDVA attached on flexible system. Firstly, the mechanical model of floating slab with NSDVA is simplified to a two-degree-of-freedom system, and theoretical expressions of NSDVA’s optimal parameters, i.e., ratio of frequency, damping and stiffness are deduced according to the fixed-point expansion theory and stability condition. Secondly, with the combination of the multi-modal control theory and the finite element method, optimal parameters of NSDVA applied to a multi-degree of freedom (MDOF) system are calculated. 3-D finite element model of floating slab-NSDVA is built in ABAQUS software, and the modal analysis of floating slab is conducted to determine the target modal and equivalent mass. Compared with the traditional Voigt type DVA, the NSDVA adopted in this paper is proved to be more effective to reduce the both floating slab and rail vibration level. The design methodology of NSDVA attached to a MDOF system presented in this paper is feasible.

Objectives: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. Methods: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1–7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. Results: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. Conclusions: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.

Summary Plasmon-induced charge transfer has drawn considerable interests and spurred rapid developments of photovoltaics and photocatalysis. Various plasmonic metal/transition metal dichalcogenide (TMD) heterostructures have been developed to promote charge separation. For plasmon-induced catalysis, the transformation of TMDs is rare, and the erosion of TMDs has not yet been reported. Here, we report the etching of two-dimensional TMDs by planar surface plasmon polaritons (SPPs). We found that SPPs can etch various TMDs into desired layers and lateral size through controlling the light power and incident direction. In aqueous media, the strong plasmonic coupling at Au/MoS2 interface generates holes in the valence band of MoS2 that can weaken its interlayer interaction. As a synergistic effect, the plasmonic hot electrons produce oxidizing H2O2 to dissolve MoS2 from the top layers. Our results provide a new perspective for understanding the plasmonic coupling at metal-TMD interfaces and a reliable route toward fabricating well-defined TMDs.

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in patients with ARDS compared with healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control ( GGPPSfl/fl) and myeloid-selective knockout ( GGPPSfl/fl LysMcre) mice were then generated. Interestingly, using an LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency upregulated the production of LPS-induced IL-6, IL-1β, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.

BackgroundIn this study, we tested whether a combination of radiomic features extracted from baseline pre-immunotherapy computed tomography (CT) images and clinicopathological characteristics could be used as novel noninvasive biomarkers for predicting the clinical benefits of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).MethodsThe data from 92 consecutive patients with lung cancer who had been treated with ICIs were retrospectively analyzed. In total, 88 radiomic features were selected from the pretreatment CT images for the construction of a random forest model. Radiomics model 1 was constructed based on the Rad-score. Using multivariate logistic regression analysis, the Rad-score and significant predictors were integrated into a single predictive model (radiomics nomogram model 1) to predict the durable clinical benefit (DCB) of ICIs. Radiomics model 2 was developed based on the same Rad-score as radiomics model 1.Using multivariate Cox proportional hazards regression analysis, the Rad-score, and independent risk factors, radiomics nomogram model 2 was constructed to predict the progression-free survival (PFS).ResultsThe models successfully predicted the patients who would benefit from ICIs. For radiomics model 1, the area under the receiver operating characteristic curve values for the training and validation cohorts were 0.848 and 0.795, respectively, whereas for radiomics nomogram model 1, the values were 0.902 and 0.877, respectively. For the PFS prediction, the Harrell’s concordance indexes for the training and validation cohorts were 0.717 and 0.760, respectively, using radiomics model 2, whereas they were 0.749 and 0.791, respectively, using radiomics nomogram model 2.ConclusionsCT-based radiomic features and clinicopathological factors can be used prior to the initiation of immunotherapy for identifying NSCLC patients who are the most likely to benefit from the therapy. This could guide the individualized treatment strategy for advanced NSCLC.

Background Early detection and prognostic prediction are crucial in improving the survival of patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we provided potential molecular markers in this study for early diagnosis and prognosis of this cancer based on The Cancer Genome Atlas (TCGA) database analysis and experimental validations. Methods Differentially expressed genes (DEGs) between HNSCC tumor and normal samples were identified by TCGA database-based analyses. Univariate and multivariate Cox regression analyses were applied, respectively, to identify survival-related DEGs and independent prognostic factors in HNSCC. Further, RT-qPCR was employed to verify expression of DEGs in cancer and adjacent tissues from HNSCC patients recruited in our hospital, in which we also clarified the correlation between candidate genes and clinicopathological characteristics and prognosis of HNSCC patients. Results TCGA data analyses yielded 59 DEGs. Cox analyses identified 13 candidate genes closely related to prognosis of HNSCC patients and established a five-gene signature comprising AC103702.2, LINC00941, RPL29, FOXL2, and CCL11. This five-gene signature could classify patients into high- and low-risk groups. The survival rate of the high-risk group was significantly lower than that of the low-risk group. Clinical tissue experiments further confirmed that AC103702.2, LINC00941, CCL11, and RPL29P19 genes were inversely associated with the prognosis of HNSCC patients, while CCL11 gene was positively associated. We also found that high-risk HNSCC patients presented a higher incidence of lymph node metastasis. Conclusion Five prognostic marker genes (AC103702.2, LINC00941, CCL11, RPL29P19, and FOXL2) as a gene cluster may serve as prognostic marker genes in HNSCC.

Cheng Wang,1 Hong Wang,2 Luming Dai,1 Jianqing Zhang,1 Lizhou Fang,1 Ling Liu,1 Weiping Fu,1 Dang Tang3 1Second Department of Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 2Department of Burns Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 3First Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of ChinaCorrespondence: Dang Tang Email tangdangdemao@126.comBackground: Chronic obstructive pulmonary disease (COPD) is often combined with type 2 diabetes mellitus (T2DM) in clinical, and with poor prognosis. In recent years, research shows that inflammation is a common characteristic of COPD and T2DM. T-helper 17 cell (Th17)/regulatory T-cell (Treg) balance controls inflammation and may be important in the pathogenesis of COPD combined with T2DM patients. This study investigated the characteristics of Th17, Treg and related inflammatory factors in COPD combined with T2DM patients and the potential mechanism.Methods: Application of flow cytometry technology, real-time fluorescent quantitative PCR and ELISA to detect the changes in peripheral blood of Th17 and Treg number and the expression of key transcription factors and related cytokines in COPD combined T2DM patients were performed.Results: Patients with COPD combined with T2DM revealed significant increase in peripheral Th17, Th17 related cytokines (IL-17A, IL-17F, IL-21, IL-23, IL-6) and transcription factor (RORγt) levels and significant decrease in Treg, Treg-related cytokines (IL-10, TGFβ 1) and transcription factor (Foxp3) as compared with patients with COPD, T2DM and healthy controls.Conclusion: Th17/Treg functional imbalance exists in patients with COPD combined with T2DM, indicating a potential role of Th17/Treg imbalance in the formation and progression of COPD combined with T2DM.Keywords: COPD combined with T2DM, Th17/Treg, cytokine, transcription factor

Background Genetic aberrations in the cyclin-dependent kinase (CDK)4 pathway occur in 82% of patients with acral melanoma (AM), which is the predominant subtype of melanoma in China. We aimed to evaluate the anti-tumour activity of palbociclib, a selective CDK4/6 inhibitor, in patients with advanced AM with CDK4 pathway gene aberrations. Methods In this phase II trial, patients with advanced AM with CDK4 or/and CCND1 gain or/and CDKN2A loss were treated with oral palbociclib (125 mg) on days 1–21 of a 28-day cycle. The primary end-point was overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Whole-exome sequencing and multiplex immunohistochemistry of the available formalin-fixed, paraffin-embedded samples of nine patients were analysed to explore the predictive biomarkers of palbociclib response. Results Fifteen patients were enrolled. Three (20.0%) patients achieved tumour shrinkage at 8 weeks, including one with confirmed partial response. At data cut-off date, treatment was ongoing for one patient. The median PFS was 2.2 mo (range: 1.5–13.3 mo; 95% confidence interval [CI]: 1.9–2.5), and the median OS was 9.5 mo (range: 2.6–14.1 mo, 95% CI: 5.7–13.4). Eight patients died due to disease progression. The most common TRAEs were leukopenia (87%; Grade III/IV, 27%), neutropenia (80%; grade III/IV, 27%), and fatigue (53%; grade III/IV, 7%). Significant JAK2 deletions and SH2B3 amplifications were observed in patients who did not achieve any clinical benefit (CB) with palbociclib treatment. MCM7 amplification or protein expression level was found to be associated with CB. Conclusions Palbociclib monotherapy demonstrated preliminary efficacy and an acceptable safety profile in advanced AM patients with CDK4 pathway aberrations. Patients with amplification or high protein levels of MCM7 were more prone to benefit from palbociclib. The JAK-STAT pathway might play a role in the mechanism of action of palbociclib in AM. Trial registration number NCT03454919 . The date of registration March 6, 2018.

As part of their efforts to control water pollution, local governments in China introduced the river chief system, whereby a named individual undertakes responsibility for protecting a specified waterway. As one of the most prominent sources of water pollution, agricultural non-point-source (NPS) pollution is becoming increasingly serious. Determining whether the river chief system, an institutional reform in China's decentralized environmental regulation regime, is effective in alleviating NPS pollution is important for the realization of green development. The effect of the river chief system on reducing agricultural NPS pollution is explored in this study using panel data from 308 Chinese counties during the period from 2004 to 2015. The results reveal that the negative impact of manure output from animal breeding operations on surface water quality is reduced with the implementation of the river chief system. However, the river chief system is ineffective in dealing with the water pollution caused by fertilizer use. Furthermore, in the current system, cooperation among river chiefs only occurs within a province. Local governments should increase their efforts in reducing fertilizer source loads and preventing fertilizer loads from entering surface waters. In addition, the central government should improve cooperation among the river chiefs in upstream and downstream provinces.

Renal cell carcinoma (RCC) has the highest mortality rate among urological cancers and tumor angiogenesis that plays a critical role in RCC progress. Epidermal growth factor-like domain multiple 7 (EGFL7) has been recently identified as a regulator in RCC tumor angiogenesis and progression. Long noncoding RNA (LncRNA) HOTAIR has been considered as a pro-oncogene in multiple cancers, but its precise mechanism of tumor angiogenesis has rarely been reported. MicroRNA-126 (miR-126) functions as a tumor suppressor in RCC. However, the underlying tumor angiogenesis mechanism of HOTAIR/miR-126 axis in RCC has not been studied. The proliferation, migration, angiogenesis, and expression of EGFL7 and related proteins in extracellular signal-regulated kinase (ERK)/activators of transcription 3 (STAT3) signal pathway were determined to examine the effect and mechanism of HOTAIR and miR-126 on RCC progress. The regulatory relationship of HOTAIR and miR-126, as well as miR-126 and EGFL7 were tested using dual-luciferase reporter assay. Aenograft RCC mice model was used to examine the effect of HOTAIR on RCC tumor growth and metastasis in vivo. HOTAIR knockdown and miR-126 overexpression suppressed the proliferation, migration, and angiogenesis of RCC cells. HOTAIR regulated EGFL7 expression by competitively binding to miR-126. Knockdown of HOTAIR significantly suppressed the RCC tumor progression and lung metastasis in vivo. These findings suggest that lncRNA HOTAIR regulate RCC angiogenesis through miR-126/EGFL7 axis and provide a new perspective on the molecular pathways of angiogenesis in RCC development, which might be potential therapeutic targets for RCC treatment.

Selumetinib (ARRY-142886) is a potent, selective, MEK1/2 inhibitor approved in the US for the treatment of children (≥ 2 years) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). We characterized population pharmacokinetics (PK) of selumetinib and its active N‐desmethyl metabolite, evaluated exposure–safety/efficacy relationships, and assessed the proposed therapeutic dose of 25 mg/m2 bid based on body surface area (BSA) in this patient population. Population PK modeling and covariate analysis (demographics, formulation, liver enzymes, BSA, patients/healthy volunteers) were based on pooled PK data from adult healthy volunteers (n = 391), adult oncology patients (n = 83) and pediatric patients with NF1-PN (n = 68). Longitudinal selumetinib/metabolite exposures were predicted with the final model. Exposure–safety/efficacy analyses were applied to pediatric patients (dose levels: 20, 25, 30 mg/m2 bid). Selumetinib and metabolite concentration–time courses were modeled using a joint compartmental model. Typical selumetinib plasma clearance was 11.6 L/h (95% CI 11.0–12.2 L/ h). Only BSA had a clinically relevant (> 20%) impact on exposure, supporting BSA-based administration in children. Selumetinib and metabolite exposures in responders (≥ 20% PN volume decrease from baseline) and non-responders were largely overlapping, with medians numerically higher in responders. No clear relationships between exposure and safety events were established; exposure was not associated with key adverse events (AEs) including rash acneiform, diarrhea, vomiting, and nausea. Findings support continuous selumetinib 25 mg/m2 bid in pediatric patients. Importantly, the updated dosing nomogram ensures that patients will receive a clinically active, yet tolerable, dose regardless of differences in BSA and allows dose reductions, if necessary.

Background. Allergic rhinitis (AR) affects millions of people and is lack of effective treatment. CD40 is an important costimulatory molecule in immunity. However, few studies have focused on the role of CD40 in AR. Methods. In this study, we built mouse model of chronic AR. The mice were divided into the AR, control, intravenous CD40 siRNA, and nasal CD40 siRNA groups ( n = 6 each). We detected OVA-sIgE, IL-4, IL-5, IL-13, IL-10, IFN-γ, and TGF-β levels in serum and supernatant by ELISA, CD40+ splenic DCs, and Foxp3+ Tregs by flow cytometry and CD40 mRNA by RT2-PCR. We also used PAS and MT stains to assess tissue remodelling. Results. (1) The OVA-sIgE, IL-4, IL-5, and IL-13 levels in the serum or supernatant of nasal septal membrane of AR mice were significantly higher than control. After treated with CD40 siRNA, those indicators were significantly decreased. The IFN-γ, IL-10, and TGF-β levels in AR mice were significantly lower than that in control and were increased by administration of CD40 siRNA. (2) AR mice had significantly fewer Foxp3+ Tregs in the spleen than control mice. After treated with CD40 siRNA, AR mice had significantly more Foxp3+ Tregs. (3) AR mice exhibited a significantly higher CD40 mRNA levels than control. Administration of CD40 siRNA significantly reduced the CD40 mRNA level. (4) The AR mice showed significantly greater collagen deposition than the control in MT staining. Applications of CD40 siRNA significantly reduced the collagen deposition in AR mice. Conclusion. CD40 siRNA therapy shows promise for chronic AR as it significantly attenuated allergic symptoms and Th2-related inflammation and upregulated Foxp3+ Tregs. CD40 plays a role in tissue remodelling in AR, which can be inhibited by CD40 siRNA application.

Wearable medical devices rely on the human body to form a small LAN around the human body, called body area network (BAN). Users can use these devices to monitor the changes of various body indicators in real time. The physiological data involved in this process belongs to personal privacy. Therefore, the security requirements of BAN are relatively high, and its current research focus is on authentication mechanisms. To meet the requirements of security and resource consumption of BAN, this paper proposes a lightweight identity authentication mechanism that meets the characteristics of BAN resource constraints. Based on the characteristics of BAN, a simple and mature star topology structure is applied to establish the network model of BAN. For the human body in normal situations and emergencies, the corresponding authentication mechanism and encryption and decryption method of physiological data are designed by using the physical unclonable function (PUF) and cloud database, physiological data, and cross-correlation algorithm. Furthermore, the formal and informal security analysis of the designed authentication mechanism proves that the authentication mechanism designed in this paper has certain security, and the lightweight authentication mechanism is simulated and evaluated. The experimental results show that compared with the benchmarking mechanism, the authentication mechanism designed in this paper solves more security problems and has certain advantages in terms of calculation cost, communication cost, and energy cost.