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Abstract Background Ventricular-arterial coupling (VAC) has garnered increasing interest in critical care. The prognostic significance of left ventricular-arterial coupling (LVAC) in this context remains a topic of debate. Objective This study aimed to explore the association between LVAC and patient outcomes in sepsis. Methods Patients with sepsis or septic shock admitted to the intensive care unit (ICU) were included. LVAC was evaluated using the arterial elastance (Ea)/left ventricular end-systolic elastance (Ees) ratio. Prognostic indicators, including 30-day mortality, length of ICU stay, mechanical ventilation (MV), changes in delta lactate levels, and oxygen index were also collected. Results A total of 388 patients were enrolled in this study. A U-shaped relationship was observed between LVAC and 30-day mortality, with an optimal LVAC value of 1.19 identified. For LVAC values above 1.19, the odds ratio (OR) for 30-day mortality was 1.07 (95% confidence interval [CI] 1.01–1.14). Below this threshold, OR was 0.85 (95% CI 0.73, 0.99). Similarly, in the curve for ICU-free days, a β value of − 8.64 (95% CI − 16.53, − 0.76) was noted for LVAC values over 1.26. For ventilator-free time, the kink point was 1.24, with significant β values on both sides of this threshold [− 226.49 (95% CI − 411.59, − 41.38) and 147.67 (95% CI 12.40, 282.93), respectively]. Conclusions This study established U-shaped associations between LVAC and various clinical outcomes in septic patients. Optimizing LVAC could potentially enhance patient prognosis. Given the slight variations in optimal LVAC values across different patient populations, individualized LVAC titration may be beneficial in improving clinical outcomes.

Abstract Objective To investigate the relationship between central venous pressure (CVP) and acute right ventricular (RV) dysfunction in critically ill patients on mechanical ventilation. Methods This retrospective study enrolled mechanically ventilated critically ill who underwent transthoracic echocardiographic examination and CVP monitoring. Echocardiographic indices including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and tricuspid lateral annular systolic velocity wave (S’) were collected to assess RV function. Patients were then classified into three groups based on their RV function and presence of systemic venous congestion as assessed by inferior vena cava diameter (IVCD) and hepatic vein (HV) Doppler: normal RV function (TAPSE ≥ 17 mm, FAC ≥ 35% and S’ ≥9.5 cm/sec), isolated RV dysfunction (TAPSE 20 mm and HV S

Abstract Background Dementia is a leading cause of disability in people older than 65 years worldwide. However, diagnosing dementia in its earliest symptomatic stages remains challenging. This study combined specific questions from the AD8 scale with comprehensive health-related characteristics, and used machine learning (ML) to construct diagnostic models of cognitive impairment (CI). Methods The study was based on the Shenzhen Healthy Ageing Research (SHARE) project, and we recruited 823 participants aged 65 years and older, who completed a comprehensive health assessment and cognitive function assessments. Permutation importance was used to select features. Five ML models using BalanceCascade were applied to predict CI: a support vector machine (SVM), multilayer perceptron (MLP), AdaBoost, gradient boosting decision tree (GBDT), and logistic regression (LR). An AD8 score ≥ 2 was used to define CI as a baseline. SHapley Additive exPlanations (SHAP) values were used to interpret the results of ML models. Results The first and sixth items of AD8, platelets, waist circumference, body mass index, carcinoembryonic antigens, age, serum uric acid, white blood cells, abnormal electrocardiogram, heart rate, and sex were selected as predictive features. Compared to the baseline (AUC = 0.65), the MLP showed the highest performance (AUC: 0.83 ± 0.04), followed by AdaBoost (AUC: 0.80 ± 0.04), SVM (AUC: 0.78 ± 0.04), GBDT (0.76 ± 0.04). Furthermore, the accuracy, sensitivity and specificity of four ML models were higher than the baseline. SHAP summary plots based on MLP showed the most influential feature on model decision for positive CI prediction was female sex, followed by older age and lower waist circumference. Conclusions The diagnostic models of CI applying ML, especially the MLP, were substantially more effective than the traditional AD8 scale with a score of ≥ 2 points. Our findings may provide new ideas for community dementia screening and to promote such screening while minimizing medical and health resources.

Abstract Background Elevated central venous pressure (CVP) is deemed as a sign of right ventricular (RV) dysfunction. We aimed to characterize the echocardiographic features of RV in septic patients with elevated CVP, and quantify associations between RV function parameters and 30-day mortality. Methods We retrospectively reviewed a cohort of septic patients with CVP ≥ 8 mmHg in a tertiary hospital intensive care unit. General characteristics and echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), pulmonary vascular resistance (PVR) as well as prognostic data were collected. Associations between RV function parameters and 30-day mortality were assessed using Cox regression models. Results Echocardiography was performed in 244 septic patients with CVP ≥ 8 mmHg. Echocardiographic findings revealed that various types of abnormal RV function can occur individually or collectively. Prevalence of RV systolic dysfunction was 46%, prevalence of RV enlargement was 34%, and prevalence of PVR increase was 14%. In addition, we collected haemodynamic consequences and found that prevalence of systemic venous congestion was 16%, prevalence of RV-pulmonary artery decoupling was 34%, and prevalence of low cardiac index (CI) was 23%. The 30-day mortality of the enrolled population was 24.2%. In a Cox regression analysis, TAPSE (HR:0.542, 95% CI:0.302–0.972, p = 0.040) and PVR (HR:1.384, 95% CI:1.007–1.903, p = 0.045) were independently associated with 30-day mortality. Conclusions Echocardiographic findings demonstrated a high prevalence of RV-related abnormalities (RV enlargement, RV systolic dysfunction and PVR increase) in septic patients with elevated CVP. Among those echocardiographic parameters, TAPSE and PVR were independently associated with 30-day mortality in these patients.

The study reported a novel L12-strengthening NiCoCrAlTi high-entropy alloy (HEA) with an outstanding synergy of tensile strength and ductility at both ambient and high temperatures. The HEA was prepared by arc melting and cold-rolling, followed by isothermal aging at designed precipitation temperatures to achieve coexistence of recrystallized and non-recrystallized grains. Transmission electron microscopy (TEM) characterization revealed a high density of rod-like and spheroidal L12 precipitates distributing in the micro/nanograins and non-recrystallized regions in the annealed specimens. The yield stress, ultimate tensile stress, and ductility of the HEA were ∼1300 MPa, 1610 MPa, and 14 % at room temperature, respectively. Such excellent mechanical properties of ∼1060 MPa, 1271 MPa, and 25 % were maintained to 600 °C, which was superior to most reported HEAs and Co- and Ni-based superalloys to date. Systematic TEM analysis unveiled at low strain, the deformation mechanism was mainly controlled by dislocations and stacking faults (SFs). With the increase in strain, the deformation mode gradually transferred to dislocations, deformation twins (DTs), and SFs. Moreover, the complex interaction between SFs and L12 precipitates, including the shearing and blocking effects, was frequently observed, contributing to the high tensile strength. Thus, the extremely high tensile strength and sustained ductility at 600 °C mainly originate from the cooperation among interaction between L12 precipitation and dislocations and extensive SFs, DTs, immobile Lomer-Cottrell (L-C) locks formed from interactions between SFs and SFs/DTs, hierarchical SFs/DTs networks, as well as hetero-deformation-induced strengthening. Such a unique deformation mechanism breaks the strength-ductility trade-off of the HEA at high temperatures.

Background Circular RNAs (CircRNAs) have been shown to be involved in the development of chronic kidney disease (CKD). This study aimed to investigate the role of Circ1647 in renal fibrosis, which is a hallmark of CKD.Methods In this study, we established a unilateral ureteral obstruction (UUO) model and delivered Circ1647 RfxCas13d knockdown plasmid into renal parenchymal cells via retrograde injection through the ureter followed by electroporation. After that, the pathological changes were determined by Hematoxylin and Eosin. Meanwhile, Immunohistochemistry, qRT-PCR and Western blot were conducted to assess the degree of fibrosis. In addition, overexpressing of Circ1647 in renal tubular epithelial cells (TCMK1) was performed to investigate the underlying mechanisms of Circ1647.Results Our results displayed that electroporation-mediated knockdown of Circ1647 by RfxCas13d knockdown plasmid significantly inhibited renal fibrosis in UUO mice as evidenced by reduced expression of fibronectin and α-SMA (alpha-smooth muscle actin). Conversely, overexpression of Circ1647 in TCMK1 cells promoted the fibrosis. In terms of mechanism, Circ1647 may mediate the PI3K/AKT Signaling Pathway as demonstrated by the balance of the phosphorylation of PI3K and AKT in vivo and the aggravated phosphorylation of PI3K and AKT in vitro. These observations were corroborated by the effects of the PI3K inhibitor LY294002, which mitigated fibrosis post Circ1647 overexpression.Conclusion Our study suggests that Circ1647 plays a significant role in renal fibrosis by mediating the PI3K/AKT signaling pathway. RfxCas13d-mediated inhibition of Circ1647 may serve as a therapeutic target for renal fibrosis in CKD.

BackgroundAssessing volume status in septic shock patients is crucial for tailored fluid resuscitation. Estimated plasma volume status (ePVS) has emerged as a simple and effective tool for evaluating patient volume status. However, the prognostic value of ePVS in septic shock patients remains underexplored.MethodsThe study cohort consisted of septic shock patients admitted to the ICU, sourced from the MIMIC-IV database. Patients were categorized into two groups based on 28-day survival outcomes, and their baseline characteristics were compared. According to the ePVS (6.52 dL/g) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low ePVS groups. A multivariable Cox regression model was utilized to evaluate the association between ePVS and 28-day mortality rate. The Kaplan–Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test.ResultsA total of 7,607 septic shock patients were included in the study, among whom 2,144 (28.2%) died within 28 days. A J-shaped relationship was observed between ePVS at ICU admission and 28-day mortality, with an increase in mortality risk noted when ePVS exceeded 6.52 dL/g. The high ePVS group exhibited notably higher mortality rates compared to the low ePVS group (28-day mortality: 26.2% vs. 30.2%; 90-day mortality: 35% vs. 42.3%). After adjustment for confounding factors, ePVS greater than 6.52 dL/g independently correlated with an increased risk of 28-day mortality (HR: 1.20, 95% CI: 1.10–1.31, p

Abstract MicroRNAs (miRNAs) play a significant role in the pathogenesis of various diseases throughout biological processes, and the accurate detection of miRNA biomarkers holds great potential for early stage disease diagnosis and treatment. In this study, a novel method is developed to detect miRNA-21, a biomarker for drug-induced liver injury, by combining target sequence recycling with G-quadruplex-based signal production. This approach is highly sensitive and does not require the use of labels. The target sequence facilitates the cyclic exposure of G-rich regions in the detection probe by toehold-mediated strand displacement processes, with the aid of the catalytic chain. The G-quadruplex sequences that have been produced subsequently interact with thioflavin T (ThT), resulting in a significant increase in its fluorescence intensity. This enhanced fluorescence is utilized for the purpose of detecting miRNA-21, with a remarkably low detection limit of 4.4 fM. The suggested technique also allows for the very specific identification of the target miRNA-21. Due to its non-label format, excellent selectivity, and sensitivity, this technology presents a straightforward and versatile approach for detecting a wide range of biomarkers in the early phases of illness detection.

Abstract Precise control of the evaporation of multiple droplets on patterned surfaces is crucial in many technological applications, such as anti‐icing, coating, and high‐throughput assays. Yet, the complex evaporation process of multiple droplets on well‐defined patterned surfaces is still poorly understood. Herein, we develop a digital twin system for real‐time monitoring of key processes on a droplet microarray (DMA), which is essential for parallelization and automation of the operations for cell culture. Specifically, we investigate the evaporation of multiple nanoliter droplets under different conditions via experiments and numerical simulations. We demonstrate that the evaporation rate is not only affected by the environmental humidity and temperature but is also strongly linked to the droplet distribution on the patterned surfaces, being significantly reduced when the droplets are densely distributed. Furthermore, we propose a theoretical method to aid in the experimental detection of volumes and pH variation of evaporating droplets on patterned substrates. This versatile and practical strategy allows us to achieve active maneuvering of the collective evaporation of droplets on a DMA, which provides essential implications for a wide range of applications including cell culture, heat management, microreactors, biochips, and so on.

The aim of this study was to assess the risk of food poisoning caused by Listeria monocytogenes in Jinhua ham processed using modern processing techniques. The parameters affecting the growth of Listeria monocytogenes during the production and sale of Jinhua ham, such as pH, water activity, temperature, lactic acid bacteria quantity, were investigated. The initial contamination rate of Listeria monocytogenes in raw pork was also evaluated. Listeria monocytogenes growth model and deactivation model were used to evaluate the exposure levels to Listeria monocytogenes in Jinhua ham. The risk of listeriosis after consumption of ready-to-eat Jinhua ham slices in different populations was explored. The results showed that the contamination level of Jinhua ham in the market was −9.47~7.05 lg CFU/g (90% confidence interval). The probability of listeriosis from ready-to-eat Jinhua ham slices consumption per portion consumed in healthy adults and at-risk populations were estimated with average values of

Abstract Background This study aimed to investigate the prevalence of multimorbidity and its associated factors among the older population in China to propose policy recommendations for the management of chronic diseases in older adults. Methods This study was conducted based on the 2021 Shenzhen Healthy Ageing Research (SHARE), and involved analysis of 346,760 participants aged 65 or older. Multimorbidity is defined as the presence of two or more clinically diagnosed or non self-reported chronic diseases among the eight chronic diseases surveyed in an individual. The Logistic analysis was adopted to explore the potential associated factors of multimorbidity. Results The prevalences of obesity, hypertension, diabetes, anemia, chronic kidney disease, hyperuricemia, dyslipidemia and fatty liver disease were 10.41%, 62.09%, 24.21%, 12.78%, 6.14%, 20.52%, 44.32%, and 33.25%, respectively. The prevalence of multimorbidity was 63.46%. The mean count of chronic diseases per participant was 2.14. Logistic regression indicated that gender, age, marriage status, lifestyle (smoking status, drinking status, and physical activity), and socioeconomic status (household registration, education level, payment method of medical expenses) were the common predictors of multimorbidity for older adults, among which, being women, married, or engaged in physical activity was found to be a relative determinant as a protective factor for multimorbidity after the other covariates were controlled. Conclusion Multimorbidity is prevalent among older adults in Chinese. Guideline development, clinical management,and public intervention should target a group of diseases instead of a single condition.

Abstract Background This study aimed to explore whether the tricuspid annular systolic excursion (TAPSE)/mitral annular systolic excursion (MAPSE) ratio was associated with the occurrence of cardiogenic pulmonary edema (CPE) in critically ill patients. Materials and methods This was a prospective observational study conducted in a tertiary hospital. Adult patients admitted to the intensive care unit who were on mechanical ventilation or in need of oxygen therapy were prospectively screened for enrolment. The diagnosis of CPE was determined based on lung ultrasound and echocardiography findings. TAPSE ≥ 17 mm and MAPSE ≥ 11 mm were used as normal references. Results Among the 290 patients enrolled in this study, 86 had CPE. In the logistic regression analysis, the TASPE/MAPSE ratio was independently associated with the occurrence of CPE (odds ratio 4.855, 95% CI: 2.215–10.641, p

Abstract Background The occurrence of a diabetic foot ulcer (DFU) is a significant complication of diabetes that often precedes the need for amputation. Autologous platelet-rich plasma (Au-PRP), a substance abundant in various growth factors and cytokines, is increasingly being recognized as a promising method for promoting ulcer healing due to its potential similarities to the physiological wound healing process. Methods The databases Medline, EMBASE, PubMed, and the Cochrane Library were systematically accessed on January 26, 2023, without any consideration for the date of publication. The selection and assessment of research studies were conducted autonomously, based on predetermined criteria and methodological standards. Two researchers gathered data and evaluated the potential for bias separately. We utilize the Stata 17.0 software to conduct data analysis and generate relevant visual representations. Results The results of the meta-analysis indicate that autologous PRP has a significant positive effect on the healing rate (RR = 1.42, 95% CI 1.30–1.56, P 0.05) when compared to conventional therapy. Conclusions Au-PRP therapy has been shown to facilitate the process of wound healing and represents a viable and secure therapeutic alternative for individuals with DFU.

Abstract Aims We aim to investigate the prognostic value of a right ventricular (RV) injury score based on the concept of RV dilation, RV systolic dysfunction, and RV‐pulmonary arterial (PA) decoupling in septic patients and to explore whether the RV injury (RVI) score can be used to grade the severity of RV dysfunction in these patients. Methods and results Septic patients admitted to the ICU were prospectively included. We collected haemodynamic and echocardiographic parameters as well as prognostic information. RV dilation was defined as right and left ventricular end‐diastolic area ratio (R/LVEDA) > 2/3. RVSD was defined as tricuspid annular plane systolic excursion (TAPSE)

The multiple etiological characteristics of acute kidney injury (AKI) have brought great challenges to its clinical diagnosis and treatment. Renal injury in critically ill patients always indicates hemodynamic injury. The Critical Care UltraSound Guided (CCUSG)-A(KI)BCDE protocol developed by the Chinese Critical Ultrasound Study Group (CCUSG), respectively, includes A(KI) diagnosis and risk assessment and uses B-mode ultrasound, Color doppler ultrasound, spectral Doppler ultrasound, and contrast Enhanced ultrasound to obtain the hemodynamic characteristics of the kidney so that the pathophysiological mechanism of the occurrence and progression of AKI can be captured and the prognosis of AKI can be predicted combined with other clinical information; therefore, the corresponding intervention and treatment strategies can be formulated to achieve targeted, protocolized, and individualized therapy.

AbstractBackground Although a study found a significant increase in serum hedgehog interacting protein (HHIP) concentrations in impaired fasting blood glucose, impaired glucose tolerance and newly diagnosed T2DM patients, the variation in circulating HHIP levels in obese individuals remains unknown.Patients and methods Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for differentially expressed genes and signal pathways. The study is comprised of a total of 452 young women, including 248 obese individuals and 204 controls. Circulating HHIP and Adipoq levels were determined with ELISA kits. Euglycemic–hyperinsulinemic clamps (EHC) and oral glucose tolerance test (OGTT) were conducted in every subject. 32 women were given metformin and 49 were given liraglutide treatment for 6 weeks. The study was registered with www.chictr.org.cn (ChiCTR2000032878 and ChiCTR1800019776).Results Obesity was significantly associated with the cAMP signal pathway, and HHIP was a secreted protein related to cAMP signalling, as determined by KEGG analysis. In this population-based cohort study, we found that the level of circulating HHIP was significantly elevated in obese women, and positively correlated with body mass index and blood glucose, blood lipid, insulin, homeostasis model assessment of insulin resistance, dehydroepiandrostenedione sulphate, and luteinizing hormone, while negatively correlated with M-value and Adipoq. Insulin resistance (IR) and ove™rweight/obesity were associated with the higher HHIP concentration. OGTT and EHC tests revealed that the levels of circulating HHIP were regulated by blood glucose but to a less extent by insulin. After therapy with metformin and liraglutide, circulating HHIP levels were decreased, whereas Adipoq levels increased significantly.Conclusions Our findings support HHIP as a potential biomarker for predicting obesity and IR. In addition, drugs targeting HHIP may be a new strategy to treat obesity.

Abstract There are many variations in the form of multifunctional radar signals. At present, the problem associated with the highest concern in the field of electronic reconnaissance is the inversion of its working mode from the reconnaissance data. A method is proposed for waveform unit classification and model reconstruction using the non‐cooperatively extracted waveform units as input data based on the hierarchical structure of multifunctional radars. The method performs multiparametric matching on waveform units subject to the constraint of the match level to obtain the similarity measure between waveform units; it then recursively expands the waveform unit pairing score matrix to complete the classification of the waveform units. Further, based on similar waveform units, the matching state matrix of the waveform unit model can be reconstructed. The feasibility and performance of the proposed method are verified by setting up typical multitype simulation experiments. The experimental results show that the proposed method can complete the classification of waveform units in the small‐data content and extensive noise intensity cases and supports the reconstruction of waveform unit models with low errors.

Lake ice thickness (LIT) is one of the key climate variables in the lake ice domain, but there are currently large uncertainties in the retrieval of LIT. We present and validate a new LIT retrieval method that utilizes ICESat-2 data to assist CryoSat-2 echo peak selection, aiming to improve the accuracy of LIT retrieval and enable data acquisition without on-site measurements. The method involves screening out similar ICESat-2 and CryoSat-2 tracks based on time and space constraints. It also involves dynamically adjusting the range constraint window of CryoSat-2 waveforms based on the high-precision lake ice surface ellipsoid height obtained from ICESat-2/ATL06 data. Within this range constraint window, the peak selection strategy is used to determine the scattering interfaces between snow-ice and ice-water. By utilizing the distance between the scattering horizons, the thickness of the lake ice can be determined. We performed the ice thickness retrieval experiment for Baker Lake in winter and verified it against the on-site measurement data. The results showed that the accuracy was about 0.143 m. At the same time, we performed the ice thickness retrieval experiment for Great Bear Lake (GBL), which does not have on-site measurement data, and compared it with the climate change trend of GBL. The results showed that the retrieval results were consistent with the climate change trend of GBL, confirming the validity of the proposed method.

Objective This study aimed to investigate the potential value of serum hypoxia-inducible factor-1α (HIF-1α) concentrations as a biomarker in patients with sepsis. Methods The enrolled patients were divided into the following four groups: the intensive care unit (ICU) control group (n = 33), infection group (n = 29), septic nonshock group (n = 40), and septic shock group (n = 94). An enzyme-linked immunosorbent assay was used to measure serum HIF-1α concentrations on ICU admission. Clinical parameters and laboratory test results were also collected. Results Serum HIF-1α concentrations were significantly higher in the infection group, septic nonshock group, and septic shock group than in the ICU control group. Moreover, HIF-1α concentrations were associated with a better predictive ability for diagnosing sepsis than the Acute Physiology and Chronic Health Evaluation II score, procalcitonin concentrations, and lactate concentrations. Patients with sepsis and HIF-1α concentrations >161.14 pg/mL had a poor prognosis. Conclusions Serum HIF-1α concentrations are a useful biomarker for the diagnosis of sepsis and predicting the prognosis of patients.

Cas12g is an endonuclease belonging to the type V RNA-guided CRISPR-Cas family. It is known for its ability to cleave RNA substrates using a conserved endonuclease active site located in the RuvC domain. In this study, we determined the crystal structure of apo-Cas12g, the cryo-EM structure of the Cas12g-sgRNA binary complex and investigated conformational changes that occur during the transition from the apo state to the Cas12g-sgRNA binary complex. The conserved zinc finger motifs in Cas12g undergo an ordered-to-disordered transition from the apo to the sgRNA-bound state and their mutations negatively impact on target RNA cleavage. Moreover, we identified a lid motif in the RuvC domain that undergoes transformation from a helix to loop to regulate the access to the RuvC active site and subsequent cleavage of the RNA substrate. Overall, our study provides valuable insights into the mechanisms by which Cas12g recognizes sgRNA and the conformational changes it undergoes from sgRNA binding to the activation of the RNase active site, thereby laying a foundation for the potential repurposing of Cas12g as a tool for RNA-editing.

Abstract This study was conducted to investigate the relationship between serum endothelial dysfunction-related biomarker levels and organ dysfunction severity in septic patients and the predictive value of these levels during sepsis. In total, 105 patients admitted to the Department of Critical Care Medicine were enrolled between September 2020 and November 2021. Serum syndecan-1 and soluble thrombomodulin(sTM) levels were measured by enzyme-linked immunosorbent assay, and clinical and laboratory data were recorded. Enroll patients were divided into the infection (n = 28), septic nonshock (n = 31), and septic shock (n = 46) groups . Serum syndecan-1 (102.84 ± 16.53 vs. 55.38 ± 12.34 ng/ml), and sTM(6.60 ± 1.44 ng/ml vs. 5.23 ± 1.23 ng/ml, P

SARM1 is a key player in axon degeneration. Here, the authors generate a nanobody, which specifically recognizes the NMN-bound state of SARM1 and helps resolve the SARM1 structure in an intermediate state of activation.

Abstract Coherent integration of complex manoeuvering targets at high speed and acceleration causes range and Doppler frequency migration and lead to large computational burdens and parameter estimation error. To solve this, the geometric‐auxiliary location rotation transform (GLRT), fast parameter estimation method, and periodic, scaled generalised, high‐order ambiguity function (PSGHAF) were proposed for this study. The quadratic range migration was corrected using the second‐order keystone transform. The GLRT uses the geometrical relationship between the rotation angle and trajectory projection to estimate the velocity and initial range in different noise environments without searching for multidimensional parameters. Thereafter, the high‐acceleration and jerk estimations of the target signal are obtained using PSGHAF, which uses the periodicity of discrete Fourier transformation (DFT) to extend the estimation scope of acceleration. This avoids estimation errors without changing the radar system parameters. Compared with others, the proposed algorithm has a lower computational complexity and improved detection performance. Numerical simulations and real data from unmanned aerial vehicles demonstrate the efficacy of the proposed solution.

Emerging drug resistance is generating an urgent need for novel and effective antibiotics. A promising target that has not yet been addressed by approved antibiotics is the bacterial DNA gyrase subunit B (GyrB), and GyrB inhibitors could be effective against drug-resistant bacteria, such as methicillin-resistant S. aureus (MRSA). Here, we used the 4-hydroxy-2-quinolone fragment to search the Specs database of purchasable compounds for potential inhibitors of GyrB and identified AG-690/11765367, or f1, as a novel and potent inhibitor of the target protein (IC50: 1.21 µM). Structural modification was used to further identify two more potent GyrB inhibitors: f4 (IC50: 0.31 µM) and f14 (IC50: 0.28 µM). Additional experiments indicated that compound f1 is more potent than the others in terms of antibacterial activity against MRSA (MICs: 4–8 µg/mL), non-toxic to HUVEC and HepG2 (CC50: approximately 50 µM), and metabolically stable (t1/2: > 372.8 min for plasma; 24.5 min for liver microsomes). In summary, this study showed that the discovered N-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides are novel GyrB-targeted antibacterial agents; compound f1 is promising for further development.

Abstract Background To explore whether hepatic vein systolic filling fraction (SFF) is associated with central venous pressure (CVP) and right ventricular (RV) systolic function in critically ill patients. Methods Adult patients admitted to ICU with echocardiographic examination were retrospectively enrolled. Echocardiographic parameters including hepatic vein systolic velocity (S) and diastolic phase velocity (D) and haemodynamic information at the time of echo examination were collected. RV systolic dysfunction was defined as tricuspid annular plane systolic excursion (TAPSE)

Oxidative stress is caused by an imbalance in oxidant/antioxidant processes and is a critical process in pulmonary diseases. As no truly effective therapies exist for lung cancer, lung fibrosis and chronic obstructive pulmonary disease (COPD), at present, it is important to comprehensively study the relationship between oxidative stress and pulmonary diseases to identify truly effective therapeutics. Since there is no quantitative and qualitative bibliometric analysis of the literature in this area, this review provides an in-depth analysis of publications related to oxidative stress and pulmonary diseases over four periods, including from 1953 to 2007, 2008 to 2012, 2013 to 2017, and 2018 to 2022. Interest in many pulmonary diseases has increased, and the mechanisms and therapeutic drugs for pulmonary diseases have been well analyzed. Lung injury, lung cancer, asthma, COPD and pneumonia are the 5 most studied pulmonary diseases related to oxidative stress. Inflammation, apoptosis, nuclear factor erythroid 2 like 2 (NRF2), mitochondria, and nuclear factor-κB (NF-κB) are rapidly becoming the most commonly used top keywords. The top thirty medicines most studied for treating different pulmonary diseases were summarized. Antioxidants, especially those targeting reactive oxygen species (ROS) in specific organelles and certain diseases, may be a substantial and necessary choice in combined therapies rather than acting as a single “magic bullet” for the effective treatment of refractory pulmonary diseases.

PurposePrevious studies have revealed that elevated mean central venous pressure (CVP) was associated with poor prognosis in specific patient groups. But no study explored the impact of mean CVP on prognosis of patients who underwent coronary artery bypass grafting surgery (CABG). The purpose of this study was to investigate the impacts of elevated CVP and its time-course on clinical outcomes of patients who underwent CABG and potential mechanisms.MethodsA retrospective cohort study was performed based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. We first identified the CVP during specific period with the most predictive value. Patients were categorized into the low-CVP and high-CVP group on the basis of the cut-off value. A propensity score matching was used to adjust covariates. The primary outcome was a 28-day mortality. The secondary outcomes were 1-year mortality and in-hospital mortality, the length of intensive care unit (ICU) stay and hospitalization, acute kidney injury incidence, use of vasopressors, duration of ventilation and oxygen index, and lactate levels and clearance. Patients in the high-CVP group were categorized into the “second day CVP ≤ 13.46 mmHg” group and the “second day CVP > 13.46 mmHg” group, respectively, and the clinical outcomes were the same as before.ResultsA total of 6,255 patients who underwent CABG were picked from the MIMIC-IV database, of which 5,641 CABG patients were monitored by CVP measurement during the first 2 days after ICU admission and 206,016 CVP records were extracted from the database. The mean CVP during the first 24 h was the most correlative and statistically significant for the 28-day mortality. The risk of the 28-day mortality was increased in the high-CVP group [OR 3.45 (95% CI: 1.77–6.70; p

Critical illness is often accompanied by a hemodynamic imbalance between macrocirculation and microcirculation, as well as mitochondrial dysfunction. Microcirculatory disorders lead to abnormalities in the supply of oxygen to tissue cells, while mitochondrial dysfunction leads to abnormal energy metabolism and impaired tissue oxygen utilization, making these conditions important pathogenic factors of critical illness. At the same time, there is a close relationship between the microcirculation and mitochondria. We introduce here the concept of a “critical unit”, with two core components: microcirculation, which mainly comprises the microvascular network and endothelial cells, especially the endothelial glycocalyx; and mitochondria, which are mainly involved in energy metabolism but perform other non-negligible functions. This review also introduces several techniques and devices that can be utilized for the real-time synchronous monitoring of the microcirculation and mitochondria, and thus critical unit monitoring. Finally, we put forward the concepts and strategies of critical unit-guided treatment.

Sepsis-induced myocardial dysfunction is common. In addition to acute coronary syndrome, at least two types of left ventricular dysfunction can occur in septic patients: typical septic cardiomyopathy (SC) and sepsis-related takotsubo cardiomyopathy (ST). Although the definition of septic cardiomyopathy is based on left ventricular (LV) systolic dysfunction, both ventricles can be affected. In this context, it has been increasingly recognized that right ventricular (RV) systolic dysfunction is associated with long-term prognosis in septic patients. Unlike typical SC, ST patients usually displayed LV apical and circumferential mid-ventricular hypokinesia and basal hypercontractility. Timely and precise evaluation of heart dysfunction in sepsis patients is not easy but obviously mandatory. Further studies are still warranted regarding the mechanism, evaluation, and management of septic cardiomyopathy.

Abstract The purpose of this study is to determine whether the levels of serum Sirt3 correlate with disease severity and perfusion indicators in septic patients, as well as to assess the clinical value of Sirt3 as a potential novel marker for sepsis diagnosis and mortality prediction. A total of 79 patients in the ICU were included in the study, of which 28 were postoperatively noninfectious and the remaining 51 patients were all diagnosed with sepsis during the study period. The levels of Sirt3 were detected and dynamically monitored by enzyme-linked adsorption method, Pearson or Spearman coefficient for correlation analysis between Sirt3 and clinical indicators, ROC curve for evaluation of diagnosis and mortality prediction, Kaplan–Meier method for the significance of Sirt3 in 28-day survival. The serum levels of Sirt3 were lower in the sepsis patients on day 1 (P

Abstract Background Appropriate iodine intake for adults is essential to reduce the prevalence of thyroid diseases, but there is little research data on iodine requirement of Chinese population. This study aimed to explore the iodine requirement of young adults to maintain a healthy status based on ‘overflow theory’. Methods Iodine-balance experiment has been performed in this project. We conducted an 18-day study consisted of a 6-day acclimation period and 3 consecutive experimental stages in 37 Chinese healthy young adults (23 female and 14 male). Each stage was consumed for 4 days. Strictly-controlled low-iodine intake diets were provided for adults in the first period, an egg or 125mL milk was added in the second and third period, respectively. The dietary samples, 24-h urine specimens and faeces of volunteers were collected daily for assessment of iodine intake and excretion in volunteers. Results Mean values of iodine intake (22.7±3.6, 35.1±3.7, and 52.2±3.8μg/d), excretion (64.7±13.9, 62.3±12.6, and 94.3±14.5μg/d) and iodine balance (-35.2±19.5, -21.0±19.8, and -33.5±26.9μg/d) were significantly different among three periods for male (P

Biofilm formation of Vibrio parahaemolyticus enhanced its tolerance to the environment, but caused many serious problems to food safety and human health. In this paper, the effects of copper and carbenicillin (CARB) stress on the formation of the biofilms of V. parahaemolyticus organisms were studied, and RNA sequencing technology was used to compare the differences in transcriptome profiles of the biofilm-related genes of V. parahaemolyticus organisms under different sub-inhibitory stresses. The results proved that V. parahaemolyticus had a large growth difference under the two stresses, copper and CARB at 1/2 minimal inhibitory concentration (MIC), and it could form a stable biofilm under both stress conditions. The amount of biofilm formed under CARB stress was significantly higher than that of copper stress (p

Introduction The incidence and prevalence of disability and cognitive impairment, which are age-related, increase as China has become an ageing society. This study aims to establish the Shenzhen Ageing Cohort Study (SZ-ageing) to explore the epidemiological situation, risk factors and biomarkers of disability and cognitive impairment among Chinese elderly individuals.Methods About 3000 participants aged 65 years and older are to be recruited from communities in Shenzhen by using a multistage sampling method. They will receive a baseline investigation between 2022 and 2024. The comprehensive data on disability and cognitive impairment will be collected by using standardised questionnaires, standardised scale assessments, clinical measurements and clinical laboratory tests. Active follow-up surveys with the same content as the baseline investigation will be conducted every 3 years.Ethics and dissemination Ethics approval has been obtained from the ethics committee of the Shenzhen Center for Chronic Disease Control (SZCCC-2022-001-01-PJ; 21 February 2022). The research findings will be presented at professional conferences and submitted to peer-reviewed journals.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200060055).

In this study, a series of CuMgAl layered double oxides (CuMgAl-LDOs) were obtained via calcination of CuMgAl layered double hydroxides (CuMgAl-LDHs) synthesised via a co-precipitation method. The results show that CuMgAl-LDO can be prepared using an optimal Cu : Mg : Al molar ratio of 3 : 3 : 2, NaOH : Na2CO3 molar ratio of 2 : 1, and calcination temperature of 600 °C. CuMgAl-LDO is a characteristic of mesoporous material with a lamellar structure and large specific surface area. The removal efficiency of sulfameter (SMD) based on CuMgAl-LDO/persulfate (PS) can reach > 98% over a wide range of initial SMD concentrations (5–20 mg L−1). The best removal efficiency of 99.49% was achieved within 120 min using 10 mg L−1 SMD, 0.3 g L−1 CuMgAl-LDO, and 0.7 mmol L−1 PS. Kinetic analysis showed that the degradation of SMD was in accordance with a quasi-first-order kinetic model. The stability of the CuMgAl-LDO catalyst was verified by the high SMD removal efficiency (> 97% within 120 min) observed after five recycling tests and low copper ion leaching concentration (0.89 mg L−1), which is below drinking water quality standard of 1.3 mg L−1 permittable in the U.S. Radical scavenging experiments suggest that SO4·− is the primary active species participating in the CuMgAl-LDO/PS system. Moreover, our mechanistic investigations based on the radical scavenging tests and X-ray photoelectron spectroscopy (XPS) results indicate that Cu(II)–Cu(III)–Cu(II) circulation is responsible for activating PS in the degradation of SMD and the degradation pathway for SMD was deduced. Accordingly, the results presented in this work demonstrate that CuMgAl-LDO may be an efficient and stable catalyst for the activation of PS during the degradation of organic pollutants.

Abstract Upon vascular injury, vascular smooth muscle cells (VSMCs) change from a contractile phenotype to a synthetic phenotype, thereby leading to atherogenesis and arterial restenosis. Myocardin (MYOCD) is essential for maintaining the contractile phenotype of VSMCs. Deletion of MYOCD in VSMCs triggers autophagy. However, the molecular mechanism underlying the effect of MYOCD on autophagy is not clear. In this study, knockdown of MYOCD in human aortic VSMCs (HA-VSMCs) triggered autophagy and diminished the expression of SMC contractile proteins. Inhibition of autophagy in MYOCD-knockdown cells restored the expression of contractile proteins. MYOCD activated the transcription of miR-30a by binding to the CArG box present in its promoter, as confirmed by luciferase reporter and chromatin immune coprecipitation assays, while miR-30a decreased the expression of autophagy protein-6 (ATG6, also known as beclin1) by targeting its 3′UTR. Restoring the expression of miR-30a in MYOCD-knockdown cells upregulated the levels of contractile proteins. Treatment of VSMCs with platelet-derived growth factor type BB (PDGF-BB) resulted in the transformation of VSMCs to a proliferative phenotype. A low level of miR-30a was observed in PDGF-BB-treated HA-VSMCs, and re-expression of miR-30a led to a decrease in proliferative marker expression. Furthermore, using a wire injury mouse model, we found that miR-30a expression was significantly downregulated in the arterial tissues of mice and that restoration of miR-30a expression at the injured site abolished neointimal formation. Herein, MYOCD could inhibit autophagy by activating the transcription of miR-30a and that miR-30a-mediated autophagy defects could inhibit intimal hyperplasia in a carotid arterial injury model.

Abstract Apolipoproteins exert a key role on glucose metabolism; however, scarce data have examined the relationship between apolipoproteins and glycated haemoglobin (HbA1c) in Chinese adults. This study determined the cross-sectional and longitudinal associations of serum Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and the ApoB/A1 ratio with HbA1c in Chinese adults. A total of 1448 subjects (584 men and 864 women) aged 54.8 years were included in a baseline survey, and the concentrations of Apo and HbA1c were measured. A total of 826 participants were followed up approximately once after 3.94 ± 0.62 years. In cross-sectional analysis, serum ApoA1 was inversely associated with HbA1c, while ApoB and the ApoB/A1 ratio were positively associated with HbA1c. After further adjusting for the potential covariates, a higher ApoA1 was associated with lower HbA1c (Quartile 4 [Q4] vs. Q1 = 5.673% vs. 5.796%, P-trend = 0.014). In contrast, positive association of ApoB concentration and the ApoB/A1 ratio with HbA1c level were showed (Q4 vs. Q1 = 5.805% vs. 5.589% for ApoB; Q4 vs. Q1 = 5.841% vs. 5.582% for ApoB/A1 ratio). The longitudinal results showed no significant associations of ApoA1, ApoB levels and the ApoB/A1 ratio with HbA1c changes (all P-trends > 0.05). Path analysis suggested that body mass index did not have mediating effect on Apo-HbA1c association. Our findings revealed that higher ApoA1, lower ApoB concentrations and the ApoB/A1 ratio were associated with lower HbA1c level in Chinese adults.

In recent years, the large Low Earth Orbit (LEO) constellations have become a hot topic due to their great potential to improve the Global Navigation Satellite Systems (GNSS) positioning performance. One of the important focus is how to obtain the accurate and reliable orbits for these constellations with dozens of LEO satellites. The GNSS-based Precise Orbit Determination (POD) will be exclusively performed to achieve this goal, where the Integer Ambiguity Resolution (IAR) plays a key role in acquiring high-quality orbits. In this study, we present a comprehensive analysis of the benefit of the single-receiver IAR in LEO POD and discuss its implication for the future LEO constellations. We perform ambiguity-fixed LEO POD for four typical missions, including Gravity Recovery and Climate Experiment (GRACE) Follow-On (GRACE-FO), Swarm, Jason-3 and Sentinel-3, using the Uncalibrated Phase Delay (UPD) products generated by our GREAT (GNSS+ REsearch, Application and Teaching) software. The results show that the ambiguity fixing processing can significantly improve the accuracy of LEO orbits. There are negligible differences between our UPD-based ambiguity-fixed orbits and those based on the Observable Signal Bias (OSB) and Integer Recovery Clock (IRC) products, indicating the good-quality of UPD products we generated. Compared to the float solution, the fixed solution presents a better consistency with the external precise science orbits and the largest accuracy improvement of 5 mm is achieved for GRACE-FO satellites. Meanwhile, the benefit can be observed in laser ranging residuals as well, with a Standard Deviation (STD) reduction of 3–4 mm on average for the fixed solutions. Apart from the absolute orbits, the relative accuracy of the space baseline is also improved by 20–30% in the fixed solutions. The result demonstrates the superior performance of the ambiguity-fixed LEO POD, which appears as a particularly promising technique for POD of future LEO constellations.

Abstract. Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.

The gearbox is an important component of a wind turbine (WT). Once the gearbox is damaged, problems such as long-term maintenance and high maintenance costs will occur. Therefore, it is necessary to carry out on-line condition monitoring (CM) of WTs. Because a large amount of data is accumulated by the supervisory control and data acquisition (SCADA) system, CMs based on data-driven methods have been widely investigated. In this paper, a CM method that is based on the KNN regression method and bagging ensemble strategy is proposed. The proposed method is validated by SCADA data collected from a field WT. The results show that the ensemble model can achieve the desired estimation accuracy and improve the operation efficiency by approximately 30%.

Microporous carbon attracts attention as an electrode material for supercapacitors. However, a large number of deep and distorted mesoporous and macroporous structures are usually created by non-uniform etching, resulting in underutilized internal space. Homogeneous activation has been considered by researchers as a necessary condition for the formation of interconnected microporous structures in carbon materials. Herein, a simple strategy of hydrothermal introduction of defects followed by homogeneous activation for the preparation of microporous carbon was developed for the synthesis of electrode materials for high-performance supercapacitors. The optimized sample with defect-enriched microporous structure and large specific surface area has a specific capacity of 315 F g−1 (1 A g−1) in KOH solution, and the assembled symmetric supercapacitor achieves a high energy density of 7.3 Wh kg−1 at a power density of 250 W kg−1. This work is interesting because it not only demonstrates that rational design of electrode materials is important to boost the performance of supercapacitors, but also provides inspiration for the design of efficient supercapacitors in the future.

We present a novel fast synthetic aperture radar (SAR) image simulation method based on the echo matrix cell algorithm including multiple scattering. To improve the efficiency of SAR image simulation while ensuring the fidelity of the simulated results, we first discretized the target facets set in the SAR beams footprint into lattice targets using the range-Doppler (RD) imaging geometry model and provided the basis for simulating electromagnetic wave transmission. Based on the simulation of electromagnetic waves transmission, we used the ray tracing algorithm to calculate the multiple backscattering field including multi-polarimetric information and various material properties. Then, based on the echo matrix cell algorithm, we set the echo matrix cell as the subfield of the target backscattering field and designed the CUDA kernel function to implement a computation parallelization for SAR echo generation. All the echo matrix cells are traversed in parallel to obtain the total backscattering field of the target, reproducing the time-varying characteristic of the backscatter coefficient for each lattice target within the synthetic aperture time. The echo signal is processed using the RD imaging algorithm to obtain the simulated SAR image. Finally, we select some targets including aircraft carrier and airplane models for simulation tests. The computation efficiency is improved over 170-fold by comparing the computations of the proposed method and CPU single-thread. We also performed some qualitative and quantitative evaluations on the fidelity of the simulated SAR images. The experimental results verify the effectiveness of the proposed method.

DNA hydrogels have gained significant attention in recent years as one of the most promising functional polymer materials. To broaden their applications, it is critical to develop efficient methods for the preparation of bulk-scale DNA hydrogels with adjustable mechanical properties. Herein, we introduce a straightforward and efficient molecular design approach to producing physically pure DNA hydrogel and controlling its mechanical properties by adjusting the degree of hydrogen bonding in ultralong single-stranded DNA (ssDNA) precursors, which were generated using a dual rolling circle amplification (RCA)-based strategy. The effect of hydrogen bonding degree on the performance of DNA hydrogels was thoroughly investigated by analyzing the preparation process, morphology, rheology, microstructure, and entrapment efficiency of the hydrogels for Au nanoparticles (AuNPs)–BSA. Our results demonstrate that DNA hydrogels can be formed at 25 °C with simple vortex mixing in less than 10 s. The experimental results also indicate that a higher degree of hydrogen bonding in the precursor DNA resulted in stronger internal interaction forces, a more complex internal network of the hydrogel, a denser hydrogel, improved mechanical properties, and enhanced entrapment efficiency. This study intuitively demonstrates the effect of hydrogen bonding on the preparation and properties of DNA hydrogels. The method and results presented in this study are of great significance for improving the synthesis efficiency and economy of DNA hydrogels, enhancing and adjusting the overall quality and performance of the hydrogel, and expanding the application field of DNA hydrogels.

BackgroundEsophageal pressure (Pes) can be used as a reliable surrogate for pleural pressure, especially in critically ill patients requiring personalized mechanical ventilation strategies. How to choose the proper esophageal balloon filling volume and then find the optimal value of esophageal pressure remains a challenge. The study aimed to assess the feasibility of catheters for Pes monitoring in mechanically ventilated patients.Materials and methodsTwelve patients under pressure-controlled mechanical ventilation were included in this study. Raw esophageal pressure was recorded at different balloon filling volumes. Then, the P-V curves were determined. VWORK was the intermediate linear section on the end-expiratory P-V curve, and VBEST was the filling volume providing the maximum difference between Pes at end-inspiration and end-expiration. The raw value of Pes was recorded, and the calibrated values of Pes were calculated by calculating the esophageal wall pressure (Pew) and esophageal elastance (Ees).ResultsTwenty-four series of Pes measurements were performed. The mean VMIN and VMAX were 2.17 ± 0.49 ml (range, 1.0–3.0 ml) and 6.79 ± 0.83 ml (range, 5.0–9.0 ml), respectively, whereas VBEST was 4.69 ± 0.16 ml (range, 2.0–8.0 ml). Ees was 1.35 ± 0.51 cm H2O/ml (range, 0.26–2.38 cm H2O/ml). The estimated Pew at VBEST was 3.16 ± 2.19 cm H2O (range, 0–7.97 cm H2O). Patients with a body mass index (BMI) ≥ 25 kg/m2 had a significantly lower VMAX (5.88 [5.25–6] vs. 7.25 [7–8] ml, p = 0.006) and a significantly lower VBEST (3.69 [2.5–4.38] vs. 5.19 [4–6] ml, p = 0.036) than patients with a BMI < 25 kg/m2. Patients with positive end-expiratory pressure (PEEP) ≥ 10 cm H2O had a lower VMIN and VBEST than patients with PEEP < 10 cm H2O, P > 0.05. Patients in the supine position had a higher esophageal pressure than those in the prone position with the same balloon filling volume.ConclusionsCalibration of esophageal pressure to identify the best filling volume of esophageal balloon catheters is feasible. The esophageal pressure can be influenced by BMI, PEEP, and position. It is necessary to titrate the optimal inflation volume again when the PEEP values or the positions change.

ObjectiveGPHB5 has been found to be associated with glucose and lipid metabolism in animal studies. However, the association of GPHB5 with IR and metabolic disorders remains unknown, and there is a lack of research in humans. Our aim in this study was to investigate the relationship between circulating GPHB5 and metabolic disorders in humans.MethodsBioinformatics analysis was performed to understand the relationship between GPHB5 and metabolic disorders. GPHB5 mRNA expression in mice and rats was determined using RT-qPCR. Circulating GPHB5 concentrations were measured with an ELISA kit. EHC and OGTT were performed in humans.ResultsBioinformatics analysis shows that GPHB5 is associated with metabolic disorders and PCOS. GPHB5 mRNA expression levels in the metabolic-related tissues of HFD-fed mice, db/db and ob/ob mice, and PCOS rats were significantly higher than those of WT mice or rats. In human studies, we find that circulating GPHB5 levels were significantly higher in women with IR and PCOS. GPHB5 levels were positively correlated with age, BMI, WHR, BP, FBG, 2 h-BG, FIns, 2 h-Ins, TC, LDL-C, HbA1c, and FFA, but negatively correlated with adiponectin. Furthermore, GPHB5 was positively correlated with DHEAS and FAI, while negatively correlated with SHBG, FSH, SHBG and FSH. The increased GPHB5 concentration was related to IR and PCOS. After the treatment of metformin, GLP-1RA (Lira), and TZDs, circulating GPHB5 levels were decreased.ConclusionsOur results reveal that circulating GPHB5 could be a biomarker and potential therapeutic target for IR and PCOS in women.

Abstract Introduction Right ventricle (RV) dilation in combination with elevated central venous pressure (CVP), which is a state of RV congestion, is seen as a sign of RV failure (RVF). On the other hand, RV systolic function is usually assessed by tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). This study aimed to investigate the prevalence and prognostic value of RVF and RV systolic dysfunction (RVSD) in septic patients. Methods Mechanically ventilated sepsis and septic shock patients were included. We collected haemodynamic and echocardiographic parameters as well as prognostic information including mechanical ventilation duration, length of ICU stay and 30-day mortality. RVF was defined as a right and left ventricular end-diastolic area ratio ≥ 0.6 in combination with CVP ≥ 8 mmHg. RVSD was defined as TAPSE

BackgroundSepsis-induced cardiomyopathy significantly increased the mortality of patients with sepsis. The diagnostic criteria for septic cardiomyopathy has not been unified, which brings serious difficulties to clinical treatment. This study aimed to provide evidence for the early identification and intervention in patients with sepsis by clarifying the relationship between the ultrasound phenotype of septic cardiomyopathy and the prognosis of patients with sepsis.MethodsThis was a multicenter, prospective cohort study. The study population will consist of all eligible consecutive patients with sepsis or septic shock who meet the Sepsis 3.0 diagnostic criteria and were aged ≥18 years. Clinical data and echocardiographic measurements will be recorded within 2 h, at the 24th hour, at the 72nd hour, and on the 7th day after admission. The prevalence of each phenotype will be described as well, and their association with prognosis will be analyzed statistically.DiscussionTo achieve early recognition, prevent reinjury, achieve precise treatment, and reduce mortality in patients with sepsis, it is important to identify septic cardiac alterations and classify the phenotypes at all stages of sepsis. First, there is a lack of studies on the prevalence of each phenotype in Chinese populations. Second, each phenotype and its corresponding prognosis are not clear. In addition, the prognosis of patients with normal cardiac ultrasound phenotypes vs. those with suppressed or hyperdynamic cardiac phenotypes is unclear. Finally, this study was designed to collect data at four specific timing, then the timing of occurrence, duration, changes over time, impact to outcomes of each phenotype will probably be found. This study is expected to establish a standard and objective method to assess the ultrasound phenotype of septic cardiomyopathy due to its advantages of visualization, non-invasiveness and reproducibility, and to provide more precise information for the hemodynamic management of septic patients. In addition, this research will promote the clinical application of critical care ultrasound, which will play an important role in medical education and make ultrasound the best method to assess cardiac changes in sepsis.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05161104, identifier NCT05161104.