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Abstract Background Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. Objective To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. Methods The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. Results The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P

It has been reported in observation studies that psychiatric traits increase the risk of urolithiasis, but the causal association between them remains to be systematically reveal. Thus, this study aims to estimate the causal effect of psychiatric traits on urinary stones, utilizing Mendelian randomization (MR) analyses. In the study, we collected data of eight psychiatric traits from summary-level genome-wide association studies (GWAS), including attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder (MDD), schizophrenia, insomnia, mood swing, anxiety and neuroticism. FinnGen consortium and BioBank Japan provided the GWAS data of urolithiasis. Three MR methodswere used in the study, in which inverse variance-weighted was employed as the primary analytic tool of causal reference. Furthermore, a meta-analysis combining the results from FinnGen and BioBank Japan was performed. In FinnGen, inverse variance-weighted analysis revealed that mood swing (p = 0.023, odds ratio (OR): 2.272, 95% confidence interval (CI): 1.122–4.600), neuroticism (p = 0.032, OR: 1.086, 95% CI: 1.007–1.171) and MDD (p = 0.014, OR: 1.259, 95% CI: 1.047–1.515) significantly increased the risk of urolithiasis, while schizophrenia (p = 0.026, OR: 0.944, 95% CI: 0.897–0.993) negatively associated with urolithiasis. In BioBank Japan, mood swing (p = 0.015, OR: 3.397, 95% CI: 1.273–9.062), neuroticism (p = 0.041, OR: 1.111, 95% CI: 1.004–1.228) and MDD (p = 0.006, OR: 1.435, 95% CI: 1.107–1.861) were found to have significant causality with urolithiasis. Combining meta-analysis revealed that mood swing (p = 0.001, OR: 2.606, 95% CI: 1.470–4.620), neuroticism (p = 0.003, OR: 1.095, 95% CI: 1.031–1.163) and MDD (p = 0.0003, OR: 1.316, 95% CI: 1.132–1.530) significantly increase the risk of urinary calculus, while schizophrenia (p = 0.04, OR: 0.959, 95% CI: 0.922–0.997) decrease the risk of urinary stones formation to our surprise.

Abstract Background High clinical value national reimbursement anticancer medications (NRAMs) are pivotal treatments for patients with cancer. However, the availability of NRAMs in medical institutions is unknown. This study aimed to assess the availability of NRAMs in national and provincial medical institutions. Methods This cross-sectional study utilized national health insurance data to access the availability of NRAMs in national and provincial medical institutions. Further statistical analyses and visualizations were conducted in terms of medical institution level and daily cost. Using the Spearman’s rank correlation test (α = 0.05), we calculated the correlation between the availability rates of NRAMs and their negotiation access time, daily cost, per capita disposable income, provincial gross product, and number of policy releases. Results Overall, 81 NRAMs, with an average availability rate of approximately 1.01% nationwide, were included. There were significant differences between provinces for each drug, and the availability of NRAMs gradually decreased in tertiary (13.41%), secondary (1.58%), and primary medical institutions (

Abstract Background The diagnosis of ICU-acquired weakness (ICUAW) may be delayed due to the complexity of critically ill patients. This study aimed to investigate the value of ultrasound measurements of rectus femoris cross-sectional area (RFCSA) in predicting ICUAW in patients undergoing invasive mechanical ventilation. Methods This was a prospective cohort study of patients undergoing mechanical ventilation for at least 48 h. RFCSA was measured using ultrasound in patients upon ICU admission and followed until discharge. Using the Medical Research Council score as the gold standard, we evaluated the diagnostic value of ultrasound measurements in predicting ICUAW. Kaplan–Meier curves were constructed to evaluate and compare the length of ICU stay and duration of invasive mechanical ventilation between patients with and without ICUAW. Results Among the 76 patients, 34 (44.7%) were diagnosed with ICUAW using the Medical Research Council score as the gold standard. The RFCSA atrophy rate between day 1 and day 3 was significantly higher in the ICUAW group (7.9 ± 2.8% vs. 4.3 ± 2.1%, p

In this study, the effects of surface treatment namely electro-pulsing followed by laser shock peening (EP-LSP) on wear resistance properties of Ti–6Al–4V alloy are investigated. It was compared with samples treated solely with laser shock peening (LSP) and electro-pulsing treatment (EP) to investigate the effects of different processes on the friction and wear properties of Ti–6Al–4V alloy. In addition, the friction coefficient, wear rate, wear morphology were also investigated. Finally, the wear mechanism was described in detail. The results demonstrated a significant reduction in grain size for the samples after EP-1-LSP treatments. Furthermore, compared with the as-received samples, the maximum hardness of EP-1, LSP and EP-1-LSP treated samples increased by 6.5%, 5.9%, and 19.6%, respectively, and the compressive residual stress on the surface increased by 2.4%, 15.0%, and 37.2%, respectively. Under the same friction conditions, the depth of wear scar of the samples after EP-1, LSP, and EP-1-LSP treatments decreased by 7.2%, 10.6%, and 18.5% than that of the as-received sample. The as-received samples mainly exhibited severe oxidative and adhesive wear, and the LSP and EP-1 treated samples showed slight adhesive and oxidative wear. The EP-1-LSP treated samples predominantly showed signs of abrasive wear.

Honey is rich in nutrients and has a wide range of biological activities. However, due to the different botanical origins, geographical origins, entomological origins, and maturity, honey shows significant differences in their endogenous compositions and nutritional values. Volatile organic compounds (VOCs) are closely related to the characteristic properties of honey, and can be used to characterize the differences between honey. Gas chromatography-ion mobility spectroscopy (GC-IMS) is a new technology which combines gas chromatography with ion mobility spectroscopy for the determination of VOCs. In recent years, GC-IMS has been gradually applied to entomological origins identification, geographical origin tracing, botanical origin differentiation, adulteration identification and maturity evaluation of honey, and has achieved good results, showing great application potential in honey quality evaluation. In this paper, the application research progress of GC-IMS for honey quality evaluation is summarized. It is suggested that future research should be carried out from the aspects of establishing honey GC-IMS database, developing GC-IMS equipment with fusion quantitative function, developing the technical standard of quality evaluation based on GC-IMS, and using GC-IMS in combination with other detection technologies，in order to provide reference for the application of GC-IMS for honey quality control, flavor research and product development.

Abstract Background Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co‐differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. Methods Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real‐time polymerase chain reaction, Cell Counting Kit‐8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. Results PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA‐432‐5p (miR‐432‐5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR‐433‐3p in PMECs, and upregulate zinc finger AN1‐type containing 5 (ZFAND5) expression by targeting miR‐3613‐5p in PCs. Conclusions Our results suggest that circPMS1 promotes cell proliferation through the miR‐432‐5p/DEPDC1 or miR‐432‐5p/POL2D axis in PASMCs, through the miR‐433‐3p/MXI1 axis in PMECs, and through the miR‐3613‐5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

ObjectiveEpidemics are sudden and rapidly spreading. Hospitals in underdeveloped areas are particularly vulnerable in case of an outbreak. This paper aims to assess the epidemic risk state and its change trend of hospitals in different epidemic stages, identify the key factors affecting hospital epidemic risk change, provide priority reference for hospital epidemic risk control, and enhance the hospital's ability to respond to sudden epidemics.MethodsBased on Grounded theory, the epidemic risk indicators that affect hospital safety are summarized. The concept of epidemic risk state and its random state space is proposed according to Markov chain theory. The impact of each indicator on the random risk state and its change is comprehensively assessed from two aspects: risk occurrence probability and risk loss. Finally, the assessment of the hospital epidemic risk state and its change at different stages is achieved.ResultsThe stable risk states of public hospitals in underdeveloped areas in non-epidemic stage t0, early epidemic stage t1, and outbreak stage t2 are P^t0(Sn)={0.142,0.546,0.220,0.093}, P^t1(Sn)={0.025,0.364,0.254,0.357}, and P^t2(Sn)={0.020,0.241,0.191,0.548}, respectively. In non-epidemic stage, the key factor in improving the hospital epidemic risk state is emergency funding. In early epidemic stage, the key factors in improving the hospital epidemic risk state are the training of medical staff in epidemic prevention skills and the management of public health. In outbreak state, the key factor in improving the hospital epidemic risk state is the training of medical staff in epidemic prevention skills and psychological awareness.ConclusionThis paper proposes the concept of epidemic risk state, providing an effective assessment method for the epidemic risk state and its change trend in public hospitals. According to the assessment, public hospitals in underdeveloped areas in different epidemic stages should adopt different risk control strategies to improve their current risk state. Blind risk control is inefficient and may even cause the epidemic risk to transition toward a more dangerous state.

Objective Defining the distribution of sweet spots in tight reservoirs is the focus of tight oil and gas exploration. Methods Using core observation, thin section identification, X-ray diffraction, homogenization temperature measurements of inclusions, and conventional physical property analysis, the sedimentary characteristics, reservoir characteristics, and diagenesis of Upper Palaeozoic tight sandstones in the Binchang area, southern Ordos Basin were studied in detail.The main controlling factors of reservoir formation were identified and the development model of high-quality reservoirs was established. Results The results show that sedimentary facies are the basis of reservoir formation, and the core beach microfacies of the braided river delta plain have coarse grain sizes, small pore-medium-fine throat pore structures, and relatively good reservoir physical properties. The underwater distributary channel and estuary bar in front of the meandering river delta have fine grain sizes and pore throat structures of micropore-microat throat pore structure, and the reservoir's physical properties are relatively poor. Diagenesis plays an important role in controlling the development and distribution of high-quality reservoirs. Intermittent volcanic tuff is transformed into kaolinite in acidic strata and altered into chlorite sheaths in alkaline strata, which inhibits quartz overgrowth and calcite cementation and protects the reservoir space. The secondary enlargement of quartz is mainly caused by the leaching of SiO2 from mudstone to sandstone.The main reasons for the cementation of calcite roof and floor are the filling of feldspar and the dissolution of cuttings in the middle and late stages of calcite. The microfractures formed by late tectonic transformation have no calcite cementation, which improves the physical properties of the reservoir and plays an adjusting role in the gas reservoir. There are two solution pore development zones near burial depths of 3 750 m and 3 900 m in the Binchang area. The optimal reservoir is the medium-coarse-grained sandstone rich in chlorite mantle formed by the transformation of volcanic tuffaceous matter in the dissolution pore development zone. The sub-optimal reservoir is mainly distributed in the middle and lower parts of the sand body with a greater single-body thickness, cyclicity and no mudstone interval in the dissolution pore development zone.This zone is composed mainly of medium-coarse-grained sandstone lacking chlorite film, calcite cementation and secondary enlargement of quartz are the lowest. Conclusion These research results further increase the understanding of the genesis of the development of high-quality tight sandstone reservoirs in the Upper Palaeozoic, providing important guidance for natural gas exploration and development in this area.

Abstract Background The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta‐analysis. Methods Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO‐FC), six‐minute walk distance (6MWD), N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2), were included. Results Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20 m, 95% CI: 10.74–37.67), NT‐proBNP (SMD: −0.41, 95% CI: −0.79–0.04), CI (MD: 0.47 L/min/m2, 95% CI: 0.17–0.77) and WHO‐FC (OR: 0.564, 95% CI: 0.457–0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30 L/min/m2, 95% CI: 0.15–0.46) and WHO‐FC (OR: 0.589, 95% CI: 0.376–0.922). Within 6 months of treatment, only the WHO‐FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380–0.993; MD: 0.30 L/min/m2, 95% CI: 0.16–0.45, respectively). More than 6 months of treatment significantly improved the 6MWD, WHO‐FC and NT‐proBNP (MD: 40.87 m, 95% CI: 10.97–70.77; OR: 0.557, 95% CI: 0.440–0.705; SMD: −0.61, 95% CI: −1.17–0.05, respectively). Conclusions Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6 months, selexipag exerted obvious effects, even in the low‐dosage group. This finding is important for guiding individualized treatments.

In high-speed cigarette manufacturing industries, occasional minor cosmetic cigarette defects and a scarcity of samples significantly hinder the rapid and accurate detection of defects. To tackle this challenge, we propose an enhanced single-shot multibox detector (SSD) model that uses variational Bayesian inference for improved detection of tiny defects given sporadic occurrences and limited samples. The enhanced SSD model incorporates a bounded intersection over union (BIoU) loss function to reduce sensitivity to minor deviations and uses exponential linear unit (ELU) and leaky rectified linear unit (ReLU) activation functions to mitigate vanishing gradients and neuron death in deep neural networks. Empirical results show that the enhanced SSD300 and SSD512 models increase the model's detection accuracy mean average precision (mAP) by up to 1.2% for small defects. Ablation studies further reveal that the model's mAP increases by 1.5%, which reduces the computational requirements by 5.92 GFLOPs. The model also shows improved inference in scenarios with limited samples, thus highlighting its effectiveness and applicability in high-speed, precision-oriented cigarette manufacturing industries.

This study aims to explore the application of deep learning models in multi-track music generation to enhance the efficiency and quality of music production. Considering the limited capability of traditional methods in extracting and representing audio features, a multi-track music generation model based on the Bidirectional Encoder Representations from Transformers (BERT) Transformer network is proposed. This model first utilizes the BERT model to encode and represent music data, capturing semantic and emotional information within the music data. Subsequently, the encoded music features are inputted into the Transformer network to learn the temporal relationships and structural patterns among music sequences, thereby generating new multi-track music compositions. The performance of this model is evaluated, revealing that compared to other algorithms, the proposed model achieves an accuracy of 95.98% in music generation prediction, with an improvement in precision by 4.77%. Particularly, the model demonstrates significant advantages in predicting pitch of music tracks. Hence, the multi-track music generation model proposed in this study exhibits excellent performance in accuracy and pitch prediction, offering valuable experimental reference for research and practice in the field of multi-track music generation.

Abstract Realization of stable and industrial-level H2O2 electroproduction still faces great challenge due large partly to the easy decomposition of H2O2. Herein, a two-dimensional dithiine-linked phthalocyaninato cobalt (CoPc)-based covalent organic framework (COF), CoPc-S-COF, was afforded from the reaction of hexadecafluorophthalocyaninato cobalt (II) with 1,2,4,5-benzenetetrathiol. Introduction of the sulfur atoms with large atomic radius and two lone-pairs of electrons in the C-S-C linking unit leads to an undulated layered structure and an increased electron density of the Co center for CoPc-S-COF according to a series of experiments in combination with theoretical calculations. The former structural effect allows the exposition of more Co sites to enhance the COF catalytic performance, while the latter electronic effect activates the 2e− oxygen reduction reaction (2e− ORR) but deactivates the H2O2 decomposition capability of the same Co center, as a total result enabling CoPc-S-COF to display good electrocatalytic H2O2 production performance with a remarkable H2O2 selectivity of >95% and a stable H2O2 production with a concentration of 0.48 wt% under a high current density of 125 mA cm−2 at an applied potential of ca. 0.67 V versus RHE for 20 h in a flow cell, representing the thus far reported best H2O2 synthesis COFs electrocatalysts.

Introduction: Pulmonary adenoid cystic carcinoma (PACC) is a rare, low-grade malignant salivary gland-type tumor characterized by a dormant onset and slow progression, often leading to misdiagnosis. Due to its rarity, limited cases have been reported in the literature. This report aimed to enhance clinicians’ understanding of this infrequent disease. Case Presentation: We present the case of a 41-year-old female patient diagnosed with PACC. Our report provides a comprehensive analysis of the patient’s imaging, pathology, and treatment, with a particular focus on immunohistochemical results. Importantly, we emphasize the significance of considering foreign bodies and tumors in the bronchus when encountering asthma-like symptoms unresponsive to conventional treatments. Due to the uncertain etiology and pathophysiology of PACC, there are currently no established guidelines for chemotherapy and radiotherapy. Conclusion: PACC predominantly manifests as bronchial lesions without significant clinical heterogeneity. Therefore, it is crucial to consider foreign bodies and tumors in the bronchus when dealing with asthma-like symptoms, especially in patients without chronic lung disease who do not respond to anti-infective, antispasmodic, and antiasthmatic treatments. Additionally, meticulous examination of lesions is essential for timely diagnosis and intervention, ultimately improving patient survival rates.

Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1β induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis.

Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes, in which the Indian hedgehog (IHH) and parathyroid hormone-related protein-parathyroid hormone-1 receptor (PTHrP-PTH1R) feedback loop is crucial. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) branch of the unfolded protein response (UPR) is essential for normal cartilage development. However, the precise role of ER stress effector IRE1α, encoded by endoplasmic reticulum to nucleus signaling 1 (ERN1), in skeletal development remains unknown. Herein, we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone growth. ERN1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth plates. Its deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and differentiation. XBP1s, produced by p-IRE1α-mediated splicing, binds and up-regulates PTH1R and IHH, which coordinate cartilage development. Meanwhile, ER stress cannot be activated normally in ERN1-deficient chondrocytes. In conclusion, ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER stress. ERN1 may have a potential role as a new target for cartilage growth and maturation.

BackgroundThis study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).MethodsPre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters.ResultsSignificantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05).ConclusionSerum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

Key Clinical Message We reported a novel variant in Kallmann syndrome. It not only determines the clinical importance of whole exome sequencing for identification of genetic pathogenic variants, but also enriches the ANOS1 genetic spectrum of CHH patients in Chinese population.

Currently, for years, unmanned aerial vehicles have been widely applied in a comprehensive realm. By enhancing computer photography and artificial intelligence, it can automatically discriminate against environmental objectives and detect events that occur in the real scene. The application of collaborative unmanned aerial vehicles will offer diverse interpretations which support a multiperspective view of the scene. Due to diverse interpretations of unmanned aerial vehicles usually deviates, thus, unmanned aerial vehicles require a consensus interpretation for the scenario. To previous purposes, this study presents an original consensus-based method to pilot multi-unmanned aerial vehicle systems for achieving consensus on their observation as well as constructing a group situation-based depiction of the scenario. Further, a fuzzy neural network generalized prediction control system known as a recurrent self-evolving fuzzy neural network is mainly used to ensure stability through the use of a descending gradient online learning rule. At the same time, users can think along the lines of evolutionary biological design. Unmanned aerial vehicles can be modeled as system experts for solving group problems that require the definition of conditions that best describe the scene. First, this method allows each unmanned aerial vehicle to set high-level conditions for detection events by aggregating events based on fuzzy information. These aggregated events are modeled by a fuzzy system ontology, which allows each unmanned aerial vehicle to report its preferences in conditions. Therefore, the interpretation of each drone is compressed to achieve a collective interpretation of the state. The final polls, consent and affinity polls confirmed the final decision group’s reliability ratings. The rated consensus indicates how well the collective interpretation of the scene matches each drone’s point of view.

The rapid development of the Hospital Information System has significantly enhanced the convenience of medical research and the management of medical information. However, the internal misuse and privacy leakage of medical big data are critical issues that need to be addressed in the process of medical research and information management. Access control serves as a method to prevent data misuse and privacy leakage. Nevertheless, traditional access control methods, limited by their single usage scenario and susceptibility to single point failures, fail to adapt to the polymorphic, real-time, and sensitive characteristics of medical big data scenarios. This paper proposes a smart contracts and risk-based access control model (SCR-BAC). This model integrates smart contracts with traditional risk-based access control and deploys risk-based access control policies in the form of smart contracts into the blockchain, thereby ensuring the protection of medical data. The model categorizes risk into historical and current risk, quantifies the historical risk based on the time decay factor and the doctor’s historical behavior, and updates the doctor’s composite risk value in real time. The access control policy, based on the comprehensive risk, is deployed into the blockchain in the form of a smart contract. The distributed nature of the blockchain is utilized to automatically enforce access control, thereby resolving the issue of single point failures. Simulation experiments demonstrate that the access control model proposed in this paper effectively curbs the access behavior of malicious doctors to a certain extent and imposes a limiting effect on the internal abuse and privacy leakage of medical big data.

Background Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. Methods and Results Deep RNA sequencing and quantitative real‐time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P

BackgroundThe construction of medical consortiums not only promotes active cooperation among hospitals, but also further intensifies active competition among them. The shared use of electronic health records (EHR) breaks the original pattern of benefit distribution among hospitals.ObjectiveThe purpose of this paper is to establish an incentive mechanism for the shared use EHR, and to reveal the incentive effect and mechanism of key factors, and to put forward management suggestions for solving the real conflicts.MethodsWe constructed a basic incentive model and an incentive model that introduces performance evaluation as a supervisory signal, based on analyzing the hospital cost function, the hospital benefit function, and the incentive contract function. Finally, the incentive effects of key factors before and after the introduction of performance evaluation were verified and compared using MATLAB simulation method.ResultsThe profit level and incentive coefficient of hospitals sharing EHR are independent of the amount of one-time government subsidies. Regardless of whether a performance evaluation supervisory signal is introduced or not, the incentive coefficients are increasing functions with respect to ρ, τ, but decreasing functions with respect to β, δ, γ. After the inclusion of supervisory signal of performance evaluation in the model, the ability of hospitals to use EHR has a higher impact effectiveness on improving both incentive effects and benefit levels. The impact of the value-added coefficient on the level of earnings is consistently greater than it would have been without the inclusion of the performance evaluation supervisory signal.ConclusionsEnhancing the capacity of hospitals to use EHR and tapping and expanding the value-added space of EHR are 2 key paths to promote sustainable shared use of EHR. Substantive performance evaluation plays an important role in stabilizing incentive effects.

Progranulin (PGRN) is a multifunctional growth factor involved in many physiological processes and disease states. The apparent protective role of PGRN and the importance of chondrocyte autophagic function in the progression of osteoarthritis (OA) led us to investigate the role of PGRN in the regulation of chondrocyte autophagy. PGRN knockout chondrocytes exhibited a deficient autophagic response with limited induction following rapamycin, serum starvation, and IL-1β-induced autophagy. PGRN-mediated anabolism and suppression of IL-1β-induced catabolism were largely abrogated in the presence of the BafA1 autophagy inhibitor. Mechanistically, during the process of OA, PGRN and the ATG5–ATG12 conjugate form a protein complex; PGRN regulates autophagy in chondrocytes and OA through, at least partially, the interactions between PGRN and the ATG5–ATG12 conjugate. Furthermore, the ATG5–ATG12 conjugate is critical for cell proliferation and apoptosis. Knockdown or knockout of ATG5 reduces the expression of ATG5–ATG12 conjugate and inhibits the chondroprotective effect of PGRN on anabolism and catabolism. Overexpression of PGRN partially reversed this effect. In brief, the PGRN-mediated regulation of chondrocyte autophagy plays a key role in the chondroprotective role of PGRN in OA. Such studies provide new insights into the pathogenesis of OA and PGRN-associated autophagy in chondrocyte homeostasis.

Soil-based irrigation and the partial substitution of chemical fertilizers with manure are promising practices to improve water and nitrogen (N) use efficiency. We hypothesize that their combination would simultaneously benefit potato production, tuber quality and profitability. A two-year experiment was conducted in semiarid northern China to investigate the combined effects of three water treatments [rainfed (W0), soil-based irrigation (W1), conventional irrigation (W2)] and three N treatments [no N (N0), chemical N (N1), 25% manure substitution (N2)] on these indicators, and to perform a comprehensive evaluation and correlation analysis. The results showed that water and N treatments separately affected all indicators except vitamin C content. Compared to W2, W1 significantly increased water productivity by 12% and irrigation water use efficiency (IWUE) by 30% due to 10% lower evapotranspiration and 21% lower water use. However, W1 and W2 negatively affected crude protein content. Conversely, this was compensated by the combination with N1 and N2. There were slight differences between N1 and N2 for all indicators on average across water treatments, while under W1, N2 significantly increased leaf area index (LAI) and N recovery efficiency (REN) by 18% and 29.4%, respectively, over N1. Also, comprehensive evaluations showed that W1N2 performed best, with the highest tuber yield, profit and acceptable quality. This can be explained by the increase in LAI, IWUE and REN due to the positive correlations with tuber yield and net return. Consequently, soil-based irrigation combined with 25% manure substitution had complementary effects on tuber quality and synergistic effects on potato productivity and profitability.

Abstract The rapid development of healthcare big data has brought certain convenience to medical research and health management, but privacy protection of healthcare big data is an issue that must be considered in the process of data application. Access control is one of the methods for privacy protection, but traditional access control models cannot adapt to the dynamic, continuous, and real-time characteristics of healthcare big data scenarios. In this paper, we propose an access control model based on risk quantification and usage control (RQ-UCON). The model adds a risk quantification module to the traditional UCON model to achieve privacy protection of medical data. This module classifies risks into direct and indirect risks and quantifies them based on the physician's visit history. The model stores the quantified risk values as subject attributes. The RQ-UCON model uses an improved Exponentially Weighted Moving Average (EWMA) and penalty factors to predict risk value and to update the risk values of the subject attributes in real-time. The RQ-UCON model uses agglomerative hierarchical clustering to cluster the risk values of physicians within the department, resulting in risk intervals for each physician's operational behavior. Each risk interval is stored as a condition in the RQ-UCON model. Finally, according to the model whether the subject attributes meet the model conditions to determine whether the subject has the corresponding access rights, and according to the risk interval to grant the subject the corresponding access rights. Through the final experiment, it can be seen that the access control model proposed in this paper has a certain control on the excessive access behavior of doctors and has a certain limitation on the privacy leakage of healthcare big data.

Abstract In cancer, extrachromosomal circular DNA (ecDNA), or megabase-pair amplified circular DNA, plays an essential role in intercellular heterogeneity and tumor cell revolution because of its non-Mendelian inheritance. We developed circlehunter ( https://github.com/suda-huanglab/circlehunter ), a tool for identifying ecDNA from ATAC-Seq data using the enhanced chromatin accessibility of ecDNA. Using simulated data, we showed that circlehunter has an F1 score of 0.93 at 30× local depth and read lengths as short as 35 bp. Based on 1312 ecDNAs predicted from 94 publicly available datasets of ATAC-Seq assays, we found 37 oncogenes contained in these ecDNAs with amplification characteristics. In small cell lung cancer cell lines, ecDNA containing MYC leads to amplification of MYC and cis-regulates the expression of NEUROD1, resulting in an expression pattern consistent with the NEUROD1 high expression subtype and sensitive to Aurora kinase inhibitors. This showcases that circlehunter could serve as a valuable pipeline for the investigation of tumorigenesis.

MicroRNAs (miRNAs) are versatile regulators of pulmonary arterial remodeling in idiopathic pulmonary arterial hypertension (IPAH). We herein aimed to characterize miRNAs in peripheral blood mononuclear cell (PBMC) and plasma exosomes, and investigate specific miRNA expression in pulmonary artery cells and lung tissues in IPAH. A co-dysregulated miRNA was identified from the miRNA expression profiles of PBMC and plasma exosomes in IPAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the potential function of differentially expressed miRNAs. Real-time quantitative reverse transcription polymerase chain reaction was used to validate the expression of specific miRNAs in hypoxia-induced pulmonary microvascular endothelial cells (PMECs), pulmonary artery smooth muscle cells (PASMCs), pericyte cells (PCs), and lung tissues of patients with IPAH and rats. Finally, the miRNA-mRNA mechanisms of miR-122-5p were predicted. MiR-122-5p was the only co-upregulated miRNA in PBMC and plasma exosomes in patients with IPAH. Functional analysis of differentially expressed miRNAs revealed associations with the GO terms “transcription, DNA-templated,” “cytoplasm,” and “metal ion binding” in both PBMC and plasma exosomes, KEGG pathway MAPK signaling in PBMC, and KEGG-pathway human papillomavirus infection in plasma exosomes. Hypoxic PMECs and PCs, lung tissue of patients with IPAH, and rats showed increased expression of miR-122-5p, but hypoxic PASMCs showed decreased expression. And miR-122-5p mimics and inhibitor affected cell proliferation. Finally, miR-122-5p was found to potentially target DLAT (in lung tissue) and RIMS1 (in PMECs) in IPAH. According to the dual-luciferase assay, miR-122-5p bound to DLAT or RIMS1. In studies, DLAT imbalance was associated with cell proliferation and migration, RIMS1 is differentially expressed in cancer and correlated with cancer prognosis. Our findings suggest that the miR-122-5p is involved in various biological functions in the adjacent vascular wall cells in IPAH.

BackgroundAs an application of inclusive finance in health insurance, inclusive commercial health insurance (ICHI) is a new public-private partnership-based health insurance scheme and has been vigorously promoted by the Chinese government in recent years to develop China Multi-level Health Insurance System, a system that aims to seek a mix of public and private sources to provide more affordable financial protection to all levels of society in line with their needs. However, the overall enrolment of ICHI scheme is still at a low level, and little is known about what influences residents' enrolment intentions. The aim of this study was to examine the multidimensional factors influencing residents' behavioral intentions and to develop a multivariate conceptual model to explore the psychographic process in the formation of enrolment intention.MethodsThe empirical data used for model validation were obtained from a cross-sectional study conducted in Nanjing, China, a representative pilot city of ICHI scheme in 2022. Exploratory factor analysis, ANOVA, standard multiple regression, and hierarchical multiple regression were mainly employed for hypothesis testing.ResultsThe findings revealed that involvement, perceived benefit, and perceived sacrifice are all crucial psychographic process factors in the formation of residents' enrolment intentions. Government participation positively moderates the influence path of “perceived benefit—enrolment intention” but negatively moderates the path of “perceived sacrifice—enrolment intention”. Moreover, it was discovered that perceived benefit mediates the effect of involvement on enrolment intention, while perceived sacrifice does not.ConclusionsImproving residents' perceived benefit and involvement degree of the product, as well as reducing their perceived sacrifice, are both key to increasing their enrolment intentions. This study also points out that one of the main dilemmas in the current development of ICHI scheme is the low level of involvement among residents, and that optimizing the product design to make it more relevant to residents' lives is a more beneficial strategy to increase overall involvement.

This paper studies the inference problem of index coefficient in single-index models under massive dataset. Analysis of massive dataset is challenging owing to formidable computational costs or memory requirements. A natural method is the averaging divide-and-conquer approach, which splits data into several blocks, obtains the estimators for each block and then aggregates the estimators via averaging. However, there is a restriction on the number of blocks. To overcome this limitation, this paper proposed a computationally efficient method, which only requires an initial estimator and then successively refines the estimator via multiple rounds of aggregations. The proposed estimator achieves the optimal convergence rate without any restriction on the number of blocks. We present both theoretical analysis and experiments to explore the property of the proposed method.

Extrachromosomal circular DNA (eccDNA) is a class of circular DNA molecules that originate from genomic DNA but are separate from chromosomes. They are common in various organisms, with sizes ranging from a few hundred to millions of base pairs. A special type of large extrachromosomal DNA (ecDNA) is prevalent in cancer cells. Research on ecDNA has significantly contributed to our comprehension of cancer development, progression, evolution, and drug resistance. The use of next-generation (NGS) and third-generation sequencing (TGS) techniques to identify eccDNAs throughout the genome has become a trend in current research. Here, we briefly review current advances in the biological mechanisms and applications of two distinct types of eccDNAs: microDNA and ecDNA. In addition to presenting available identification tools based on sequencing data, we summarize the most recent efforts to integrate ecDNA with single-cell analysis and put forth suggestions to promote the process.

Abstract Background Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients. Methods A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73–0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan–Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE. Results A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P

The coastal environment is characterized by high, multi-scale dynamics and the corresponding observations from a single remote sensing sensor are still facing challenges in achieving both high temporal and spatial resolution. This study proposed a spatiotemporal fusion model for coastal environments, which could fully enhance the efficiency of remote sensing data use and overcome the shortcomings of traditional spatiotemporal models that are insensitive to small-scale disturbances. The Enhanced Deep Super-Resolution Network (EDSR) was used to reconstruct spatial features in the lower spatial resolution GOCI-II data. The spatial features obtained instead of GOCI-II data were fed into the spatiotemporal fusion model, which enabled the fusion data to achieve an hour-by-hour observation of the water color and morphology information changes at 30 m resolution, including the changes in the spatial and temporal distributions of suspended particulate matter (SPM), the characterization of the vortex street caused by the bridge piers, the inundation process of the tidal flats, and coastline changes. In addition, this study analyzed the various factors affecting fusion accuracy, including spectral difference, errors in both temporal difference and location distance, and the structure of the EDSR model on the fusion accuracy. It is demonstrated that the location distance error and the spectral difference have the most significant impact on the fusion data, which may lead to the introduction of some ambiguous or erroneous spatial features.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein–protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes (ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.

The slow loris is a group of endangered small arboreal primates. In recent decades, illegal hunting and habitat degradation have led to a sharp decline in wild populations. The individuals are challenging to be identified both in captive and natural environments due to their cryptic nocturnal behavior. Computer vision has emerged as a new approach to face recognition for domestic and wild animals. We used a YOLOv5 +U-Net+VGG framework to realize the face identification of Bengal slow lorises (Nycticebus bengalensis) based on 1480 images of 30 individuals housed in Dehong Wildlife Rescue Center, China. This is the first human-annotated face image dataset of Lorisidae primates. The accuracy rate of this deep learning model set for face recognition reached 96.27 %. The results indicated that computer vision and deep learning technology could be used in individual identification of slow lorises, contributing to further study and conservation of this endangered taxa.

Due to the feasibility of the gray model for predicting time series with small samples, the gray theory is well investigated since it is presented and is currently evolved in an important manner for forecasting small samples. This study proposes a new gray prediction criterion based on the neural ordinary differential equation, which is named the neural ordinary differential gray mode. This neural ordinary differential gray mode permits the forecasting model to be learned by a training process which contains a new whitening equation. It is needed to prepare the structure and time series, compared with other models, according to the regularity of actual specimens in advance, therefore this model of neural ordinary differential gray mode can provide comprehensive applications as well as learning the properties of distinct data specimens. To acquire a better model which has highly predictive efficiency, afterward, this study trains the model by neural ordinary differential gray mode using the Runge–Kutta method to obtain the prediction sequence and solve the model. The controller establishes an advantageous theoretical foundation in adapting to novel wheels and comprehensively spreads the utilize extent of mechanical elastic vehicle wheel.

Understanding the spatial-temporal dynamics of crop nitrogen (N) use efficiency (NUE) and the relationship with explanatory environmental variables can support land-use management and policymaking. Nevertheless, the application of statistical models for evaluating the explanatory variables of space-time variation in crop NUE is still under-researched. In this study, stepwise multiple linear regression (SMLR) and Random Forest (RF) were used to evaluate the spatial and temporal variation of NUE indicators (i.e., partial factor productivity of N (PFPN); partial nutrient balance of N (PNBN)) at county scale in Northeast China (Heilongjiang, Liaoning and Jilin provinces) from 1990 to 2015. Explanatory variables included agricultural management practices, topography, climate, economy, soil and crop types. Results revealed that the PFPN was higher in the northern parts and lower in the center of the Northeast China and PNBN increased from southern to northern parts during the 1990–2015 period. The NUE indicators decreased with time in most counties during the study period. The model efficiency coefficients of the SMLR and RF models were 0.44 and 0.84 for PFPN, and 0.67 and 0.89 for PNBN, respectively. The RF model had higher relative importance of soil and climatic covariates and lower relative importance of crop covariates compared to the SMLR model. The planting area index of vegetables and beans, soil clay content, saturated water content, enhanced vegetation index in November & December, soil bulk density, and annual minimum temperature were the main explanatory variables for both NUE indicators. This is the first study to show the quantitative relative importance of explanatory variables for NUE at a county level in Northeast China using RF and SMLR. This novel study gives reference measurements to improve crop NUE which is one of the most effective means of managing N for sustainable development, ensuring food security, alleviating environmental degradation and increasing farmer's profitability.

This paper discusses how to improve the accuracy of doctors' diagnosis and how to protect the security of patients' information. First, UPHFPR (Uncertain Probability Hesitant Fuzzy Preference Relationship) is applied to select more accurate target for doctors. The framework involved an information entropy to quantify the access request risks and privacy risks when doctors access clinical data. Based on the bounded rationality hypothesis, we build a multi-player evolutionary game model of risk access control, and analyze the participants' dynamic selection strategy and evolutionary stability. The simulation experiments suggest that UPPHFPR can help doctors choose the correct work objectives by integrating doctors' diagnostic opinions; we also incorporate the risk of doctor's access behavior into the evolutionary game's profit function, which can realize risk-adaptive access control. This model avoids the disclosure of clinical data and effectively protects the patients’ privacy.

Abstract Background Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH). Methods Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP. Results Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats. Conclusion Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH.

Abstract The association between blood eosinophil (EOS) counts and arterial/venous thrombosis is unclear. We aim to explore whether EOS count is a risk factor for thrombosis. We searched several databases and preprint platforms using core terms ‘eosinophil’, ‘myocardial infarction’, ‘ischemic stroke’, and ‘venous thromboembolism’ (VTE), among others. Studies comparing the odds ratios (ORs) or risk ratios (RRs) of EOSs with the abovementioned diseases were eligible. Overall, 22 studies were included. A high EOS count was associated with acute coronary artery thrombosis events (OR: 1.23, 95% CI: 1.15–1.32), short‐term cerebral infarction and mortality (RR: 2.87, 95% CI: 1.49–5.51). The short‐term risk of VTE was more common in patients with EOS‐related diseases (RR: 6.52, 95% CI: 2.42–17.54). For coronary artery disease, a high EOS count was a protective factor against 6‐month to 1‐year mortality (RR: 0.56, 95% CI: 0.45–0.69) but was associated with long‐term mortality (RR: 1.64, 95% CI: 1.25–2.14). Therefore, we conclude that for coronary artery thrombosis, EOS count is not associated with AMI events in general population. It may be associated with NSTEMI and STEMI in CAD patients, but more studies are needed to confirm this. In addition, EOS count is associated with an increased risk of both short‐ and long‐term mortality but is not predictive of the composite endpoints. For cerebral artery thrombosis, EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short‐term prognosis. For VTEs, EOS count was a risk factor for some patients, especially those with acute‐phase EOS‐related diseases.

Abstract Hematopoietic stem cells show biological manifestations of aging, diminished hematopoietic function and abnormal differentiation, which can lead to leukemia. It is therefore important to explore the mechanism underlying hematopoietic stem cell aging to develop strategies for delaying the process. Our evaluations revealed that the number of bone marrow hematopoietic cells (BMHCs) started to decrease significantly after 45 years of age, and the number of senescent BMHCs, as determined by senescence-associated beta-galactosidase staining, gradually increased with age. In addition, BMHCs from individuals over 45 years of age presented with notably reduced proliferative capacity, increased G1-phase cell cycle arrest, and significantly decreased generation of mixed colony forming units, which suggests that BMHCs enter senescence during middle age. Furthermore, we observed significantly lower antioxidant capacity and a significant increase in oxidative damage products, a gradual increase in the expression of senescence-associated proteins and genes, and a gradual decrease in the expression of cell cycle related proteins in BMHCs after middle age. Taken together, these findings offer both a theoretical and experimental basis for better understanding of the senescence progression of BMHCs and the optimal timing for anti-senescence drug interventions in clinical practice.

Abstract Background Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). Methods CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. Results Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR

Objective We aimed to provide insight into differences in drug review decisions made by the US Food and Drug Administration’s (FDA) accelerated approval (AA) pathway and the European Medicines Agency’s (EMA) conditional marketing authorisation (CMA) pathway, and to add to the current knowledge base of drug approval processes.Design, setting, participants This cross-sectional study thoroughly examines novel oncology drugs with dual approval through FDA AA and EMA CMA between 2006 and 2021. Statistical analysis was performed from June to July 2022.Primary and secondary outcome measures The study examined the regulatory differences between regions for dually approved novel oncology drugs, including approval decisions, pivotal efficacy clinical trials, speed of review and postmarketing obligations.Results During this time period, there was a difference in the use of the FDA AA and the EMA CMA (FDA: EMA: 41.2%: 70.0%, p

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.

BackgroundDementia is more prevalent in women than in men across the world, and sex differences are reflected in the burden of dementia borne by women and men. However, a few studies have specifically analyzed the disease burden of dementia in Chinese women.ObjectiveThis article aims to raise awareness of Chinese females with dementia (CFWD), outline an effective response to future trends in China from a female perspective, and provide a reference for the scientific formulation of dementia prevention and treatment policies in China.MethodsIn this article, epidemiological data on dementia in Chinese women were obtained from the Global Burden of Disease Study 2019, and three risk factors, namely, smoking, a high body mass index, and a high fasting plasma glucose, were selected for the analysis. This article also predicted the burden of dementia in Chinese women in the next 25 years.ResultsThe prevalence of dementia, mortality, and disability-adjusted life year rates increased with age in CFWD in 2019. All three risk factors provided by the Global Burden of Disease Study 2019 showed positive correlations for the effect of disability-adjusted life years (DALYs) rates on CFWD. Among them, a high body mass index had the greatest effect (8%) and smoking had the smallest effect (6.4%). Over the next 25 years, the number of CFWD and its prevalence are expected to be on the rise, while mortality is expected to remain relatively stable and decline slightly, but deaths from dementia will continue to increase.ConclusionsThe situation arising due to the spread of dementia among Chinese women in the future is going to become a serious issue. To reduce the burden of dementia, the Chinese government should prioritize its prevention and treatment. A multi-dimensional, long-term care system involving families, community, and hospitals should also be established and supported.

Abstract Background Spinal cord injury (SCI) is a traumatic central nervous system disorder that leads to irreversible neurological dysfunction. Emerging evidence has shown that differentially expressed circular RNAs (circRNAs) after SCI is closely associated with the pathophysiological process. Herein, the potential function of circRNA spermine oxidase (circSmox) in functional recovery after SCI was investigated. Methods Differentiated PC12 cells stimulated with lipopolysaccharide (LPS) were employed as an in vitro model for neurotoxicity research. Levels of genes and proteins were detected by quantitative real‐time PCR and Western blot analysis. Cell viability and apoptosis were determined by CCK‐8 assay and flow cytometry. Western blot analysis was used to detect the protein level of apoptosis‐related markers. The levels of interleukin (IL)‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF)‐α. Dual‐luciferase reporter, RIP, and pull‐down assays were used to confirm the target relationship between miR‐340‐5p and circSmox or Smurf1 (SMAD Specific E3 Ubiquitin Protein Ligase 1). Results LPS elevated the levels of circSmox and Smurf1, but decreased the levels of miR‐340‐5p in PC12 cells in a dose‐dependent manner. Functionally, circSmox silencing alleviated LPS‐induced apoptosis and inflammation in PC12 cells in vitro. Mechanistically, circSmox directly sponged miR‐340‐5p, which targeted Smurf1. Rescue experiments showed that miR‐340‐5p inhibition attenuated the neuroprotective effect of circSmox siRNA in PC12 cells. Moreover, miR‐340‐5p suppressed LPS‐triggered neurotoxicity in PC12 cells, which was reversed by Smurf1 overexpression. Conclusion CircSmox enhances LPS‐induced apoptosis and inflammation via miR‐340‐5p/Smurf1 axis, providing an exciting view of the potential involvement of circSmox in SCI pathogenesis.

In the construction of underground engineering, the determination of surrounding rock stresses has important theoretical significance for the design of tunnel structure reliability. In this paper, the nonlinear criterion is introduced to modify and improve the friction resistance in the calculation formula of Bierbaumer’s loose surrounding rock stresses, and the improved application is carried out in view of the situation of composite formation. Due to the variability and discreteness of geotechnical parameters, combined with engineering examples, Monte Carlo random sampling is carried out for various geotechnical parameters in engineering, and the characteristics of loose surrounding rock stresses are analyzed from the perspective of statistical reliability by using the improved shallow tunnel formula. By using the standard regression coefficient, the weight influence of the parameters in various shallow surrounding rock stress formulas is analyzed, and the confidence degree of the calculated results of various formulas is analyzed from a statistical point of view, which verifies the rationality of the improved formula in the statistical sense.

Abstract Background Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH. Methods Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E2) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA. Results Many circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E2 strongly regulated it. E2 decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E2 reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E2 and miR‐21‐5p antagonist. Conclusions miR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E2 on MCT‐PH through ERβ.

Compared with incremental innovation, breakthrough innovation is essential to sustaining competitive advantage, but breakthrough innovation has the characteristics of high standards and strict requirements. As the main body and foundation of enterprises, the attitude and behavior of employees play a vital role in enterprise innovation. Based on the positive organizational behavior theory and knowledge management theory, the purpose of this paper is to investigate the relationship between psychological capital and breakthrough innovation, and we also integrate tacit knowledge sharing and task interdependence into the research framework, so as to further explore the influence mechanism of employees’ psychological capital on breakthrough innovation. Utilizing a quantitative method, this study takes employees of Yunnan coffee enterprises as investigation objects, the data was analyzed using regression analysis through SPSS 24.0, and the existence of mediation was further verified by Bootstrap test. The results showed that the psychological capital of employees have a positive impact on breakthrough innovation; tacit knowledge sharing partially mediates the relationship between psychological capital and breakthrough innovation; and task interdependence plays a moderating role, that is, the stronger the task interdependence, the stronger the influence of employee psychological capital on breakthrough innovation. This study enriches the research on the influencing factors of breakthrough innovation of Yunnan coffee industry, expands the application scenarios of the related theory, emphasizes that the importance of psychological capital and the breakthrough innovation is the result of the interaction and value-added linkage of various internal and external resources.