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Abstract Purpose To develop and validate a nomogram for predicting the overall survival (OS) of ovarian cancer patients with liver metastases (OCLM). Methods This study identified 821 patients in the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly divided in a ratio of 7:3 into a training cohort (n = 574) and a validation cohort (n = 247). Clinical factors associated with OS were assessed using univariate and multivariate Cox regression analyses, and backward stepwise regression was applied using the Akaike information criterion (AIC) to select the optimal predictor variables. The nomogram for predicting the OS of the OCLM patients was constructed based on the identified prognostic factors. Their prediction ability was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curves analysis (DCA) in both the training and validation cohorts. Results We identified factors that predict OS for OCLM patients and constructed a nomogram based on the data. The ROC, C-index, and calibration analyses indicated that the nomogram performed well over the 1, 2, and 3-year OS in both the training and validation cohorts. Additionally, in contrast to the External model from multiple perspectives, our model shows higher stability and accuracy in predictive power. DCA curves, NRI, and IDI index demonstrated that the nomogram was clinically valuable and superior to the External model. Conclusion We established and validated a nomogram to predict 1,2- and 3-year OS of OCLM patients, and our results may also be helpful in clinical decision-making.

Abstract Background Monitoring symptoms is crucial for the early detection of disease progression and timely intervention, which is essential for reducing severe cases and mortality rates in rapidly spreading pandemics, such as COVID-19. Therefore, during infectious disease pandemics, the rapid development of real-time symptom monitoring platforms is essential. This study aimed to explore the urgent development process of an electronic system for patient-reported outcome monitoring in emergency situations. Methods The development of the electronic patient-reported outcome COVID-19 symptom monitoring platform (ePRO-CoV-SM) included the following steps: (1) modifying an electronic patient-reported outcome symptom-reporting platform to assess patients with COVID-19 and validating its feasibility and sensitivity for longitudinal symptom measurement; (2) updating the system to accommodate the newly emerged severe acute respiratory syndrome coronavirus 2 BA.2.2 variant; and (3) applying it in real-world settings. Literature review, expert consultation, and subject-group discussions were used to develop symptom items. Response rate and missing item rate were used as validation indicators for ePRO-CoV-SM. Results The ePRO-CoV-SM (2.0) consists of a core set of symptom items, a WeChat mini program, an online project design backend, a management and communication front, and a database. During the 2020 verification, the response rate of ePRO symptom monitoring reached 89.47% and the item missing rate was 0.33%, the monitoring revealed that a considerable number of asymptomatic patients were experiencing undesirable symptoms during the isolation period. In its real-world application in 2022, the response rate was 85.93% and the item missing rate was 4.84%, the monitoring found the symptom burden was higher in the younger group (18–40 years old) than in the older group (40–67 years old), and over 30% of patients reported symptoms such as cough (36.08%), dry mouth (35.67%), sleep disorders (32.27%), appetite loss (32.17%), and sputum (30.79%) during the isolation period. Conclusions Electronic patient-reported outcome measurement was demonstrated to be sensitive and feasible for monitoring symptoms in patients with COVID-19. By integrating smartphone-based data collection with real-time online data transmission and secure data storage using Secure Sockets Layer encryption, an electronic platform for monitoring critical symptoms can be rapidly established in emergency situations.

BackgroundReproductive tract infections (RTIs) represent a critical public health concern impacting women’s health, particularly pronounced in developing countries. We aim to investigates the prevalence of self-reported RTI symptoms in women aged 18 to 65 and the factors influencing gynecological examination behavior and associated risks are explored.MethodsFrom May 6, 2022, to September 20, 2022, a comprehensive survey engaged 20,864 women aged 18 to 65 in 19 townships in Lueyang, Shaanxi. Each survey team, comprising a gynecologist, two female health center staff, and a master’s student, conducted face-to-face questionnaire surveys in villages and households. The questionnaire featured three sections: prevalence of self-reported RTI symptoms, gynecological examination history, and factors influencing examination behavior.ResultsThe high response rate of 98.69% yielded 20,590 valid questionnaires. Among surveyed women, 42.04% reported RTI symptoms, with a higher prevalence in those aged 30 and above, peaking at 44.88% in the 50–59 age group. Vulvar itching (24.73%), abnormal vaginal discharge (17.41%), and urinary tract irritation signs (11.73%) were most common. Older adult women (≥60) reported higher frequency and longer duration of symptoms. Only 9.88% of symptomatic women underwent gynecological examinations in 2022. Examination likelihood decreased with age, presenting a critical gap in healthcare utilization among older women. Reasons for checkups included routine checkups (47.02%), symptom concerns (41.29%), and the availability of free medical checkup programs (9.82%). Barriers included perceived lack of serious symptoms (23.7%), lack of necessity (4.41%) and lack of time (3.98%). Among those examined, 40.58% had a diagnosis of gynecological disorders, including pelvic inflammatory disease, human papilloma virus infection and cervical cancer.ConclusionWidespread RTI symptoms, particularly in perimenopausal and older women, underscore the need for enhanced healthcare. Barriers to gynecological examinations include awareness, education, and accessibility issues. Strategies must prioritize health education, routine examinations, and improved healthcare infrastructure in underdeveloped regions.

Autoimmune encephalitis (AE) is an inflammatory disease of the central nervous system characterized by the production of various autoimmune antibodies targeting neuronal proteins. The pathogenesis of AE remains elusive. Accumulating evidence suggests that lymphocytes, particularly B and T lymphocytes, play an integral role in the development of AE. In the last two decades, autoimmune neural antibodies have taken center stage in diagnosing AE. Recently, increasing evidence has highlighted the importance of T lymphocytes in the onset of AE. CD4+ T cells are thought to influence disease progression by secreting associated cytokines, whereas CD8+ T cells exert a cytotoxic role, causing irreversible damage to neurons mainly in patients with paraneoplastic AE. Conventionally, the first-line treatments for AE include intravenous steroids, intravenous immunoglobulin, and plasma exchange to remove pathogenic autoantibodies. However, a minority of patients are insensitive to conventional first-line treatment protocols and suffer from disease relapse, a condition referred to as refractory AE. In recent years, new treatments, such as rituximab or CAAR-T, which target pathogenic lymphocytes in patients with AE, have offered new therapeutic options for refractory AE. This review aims to describe the current knowledge about the function of B and T lymphocytes in the pathophysiology of AE and to summarize and update the immunotherapy options for treating this disease.

Abstract Due to the lack of direct assessment metrics, existing studies on the intensity of agricultural policies often utilize indicators such as Gross Domestic Product (GDP) of agriculture or the quantity of agricultural policies as measures. Optimizing methods for analyzing the intensity of agricultural policies will significantly impact parameter selection in agricultural policy research and the evaluation of policy effectiveness. In this study, we constructed a Chinese Agricultural Policy Corpus using agricultural policies released by various governmental agencies at the national level in China from 1982 to April 2023. We quantified the values of agricultural domain terms in the corpus and evaluated the intensity of each agricultural policy document. The validation results of this study indicate a strong correlation between the intensity of agricultural policies and agricultural GDP. The trend in agricultural GDP changes lags behind policy intensity by 2.5 years (at a 95% confidence level), thus validating the rationality of our constructed corpus, agricultural policy scoring dataset, and methodology.

Abstract Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/β-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.

Heterologous sensitization of adenylyl cyclase (AC) results in elevated cAMP signaling transduction that contributes to drug dependence. Inhibiting cullin3-RING ligases by blocking the neddylation of cullin3 abolishes heterologous sensitization, however, the modulating mechanism remains uncharted. Here, we report an essential role of the potassium channel tetramerization domain (KCTD) protein 2, 5, and 17, especially the dominant isoform KCTD5 in regulating heterologous sensitization of AC1 and morphine dependence via working with cullin3 and the cullin-associated and neddylation-dissociated 1 (CAND1) protein. In cellular models, we observed enhanced association of KCTD5 with Gβ and cullin3, along with elevated dissociation of Gβ from AC1 as well as of CAND1 from cullin3 in heterologous sensitization of AC1. Given binding of CAND1 inhibits the neddylation of cullin3, we further elucidated that the enhanced interaction of KCTD5 with both Gβ and cullin3 promoted the dissociation of CAND1 from cullin3, attenuated the inhibitory effect of CAND1 on cullin3 neddylation, ultimately resulted in heterologous sensitization of AC1. The paraventricular thalamic nucleus (PVT) plays an important role in mediating morphine dependence. Through pharmacological and biochemical approaches, we then demonstrated that KCTD5/cullin3 regulates morphine dependence via modulating heterologous sensitization of AC, likely AC1 in PVT in mice. In summary, the present study revealed the underlying mechanism of heterologous sensitization of AC1 mediated by cullin3 and discovered the role of KCTD proteins in regulating morphine dependence in mice.

Abstract In this report, we described a new technique of gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices in a porcine model. As a result, the gynecological procedures were successfully completed. The total operative time was 110 min, while the docking time was 10 min. The estimated blood loss was estimated to be 10 mL with no intraoperative complications. It revealed that gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices appeared to be feasible and safe in the porcine model and has the potential for clinical use in human beings.

Objective: This study aimed to translate and evaluate the psychometric properties of the Perinatal Missed Care Survey in China. Methods: The Perinatal Missed Care Survey was translated according to the guidelines of the cross-cultural debugging scale recommended by the American Academy of Orthopaedic Surgeons Evidence-Based Medicine Committee, including forward translation, back translation, cultural adaption, and content validation, and its Chinese version was used in a cross-sectional study conducted from February to April in 2023. A total of 491 midwives from 14 different level hospitals in southwest China were recruited through a convenience sampling method. The discrimination ability of the items was tested through item analysis, and construct validity was assessed through exploratory factory and confirmatory factor analyses. The content validity index and Cronbach’s α coefficients evaluated content validity and reliability, respectively. Results: The Chinese version’s item–total correlation coefficients ranged from 0.641 to 0.866 in part A and from 0.644 to 0.819 in part B (P

The identification of plant leaf diseases is crucial in precision agriculture, playing a pivotal role in advancing the modernization of agriculture. Timely detection and diagnosis of leaf diseases for preventive measures significantly contribute to enhancing both the quantity and quality of agricultural products, thereby fostering the in-depth development of precision agriculture. However, despite the rapid development of research on plant leaf disease identification, it still faces challenges such as insufficient agricultural datasets and the problem of deep learning-based disease identification models having numerous training parameters and insufficient accuracy. This paper proposes a plant leaf disease identification method based on improved SinGAN and improved ResNet34 to address the aforementioned issues. Firstly, an improved SinGAN called Reconstruction-Based Single Image Generation Network (ReSinGN) is proposed for image enhancement. This network accelerates model training speed by using an autoencoder to replace the GAN in the SinGAN and incorporates a Convolutional Block Attention Module (CBAM) into the autoencoder to more accurately capture important features and structural information in the images. Random pixel Shuffling are introduced in ReSinGN to enable the model to learn richer data representations, further enhancing the quality of generated images. Secondly, an improved ResNet34 is proposed for plant leaf disease identification. This involves adding CBAM modules to the ResNet34 to alleviate the limitations of parameter sharing, replacing the ReLU activation function with LeakyReLU activation function to address the problem of neuron death, and utilizing transfer learning-based training methods to accelerate network training speed. This paper takes tomato leaf diseases as the experimental subject, and the experimental results demonstrate that: (1) ReSinGN generates high-quality images at least 44.6 times faster in training speed compared to SinGAN. (2) The Tenengrad score of images generated by the ReSinGN model is 67.3, which is improved by 30.2 compared to the SinGAN, resulting in clearer images. (3) ReSinGN model with random pixel Shuffling outperforms SinGAN in both image clarity and distortion, achieving the optimal balance between image clarity and distortion. (4) The improved ResNet34 achieved an average recognition accuracy, recognition precision, recognition accuracy (redundant as it’s similar to precision), recall, and F1 score of 98.57, 96.57, 98.68, 97.7, and 98.17%, respectively, for tomato leaf disease identification. Compared to the original ResNet34, this represents enhancements of 3.65, 4.66, 0.88, 4.1, and 2.47%, respectively.

Abstract Background Literature regarding the advantages of gasless vNOTES is insufficient. The aim of our study is to compare gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. We hypothesize that compared with those in the traditional vNOTES group, hemodynamic profiles will be changed less during gasless vNOTES, while safety can be promised. Methods This is a single-center, prospective, single-blind, randomized controlled clinical trial, which has been approved by the Institutional Review Board of Chengdu Women’s and Children’s Hospital on September 27, 2022. One hundred and twenty patients will be recruited and randomly assigned to either the traditional vNOTES group or the gasless vNOTES group in a 1:1 ratio. For patients allocated to the traditional vNOTES group, after insertion of one port through the vagina, CO2 gas is infused with a pressure of 12–14 mmHg; while for those allocated to the gasless vNOTES group, a special device is used as an abdominal wall-lifting device to facilitate gasless surgery. CO2 pneumoperitoneum will not be used during the whole gasless vNOTES procedure. The primary outcome is vital signs at different time points. The secondary outcomes include surgical conversion rate, duration of surgery and anesthesia, anesthetic consumption, intraoperative estimated blood loss, VAS and PONV scores at postoperative 2 h and 24 h, administration of vasopressor drugs from the beginning of general anesthesia induction to 15 min after endotracheal intubation, including times, dosage, and type, intraoperative and postoperative complications, time of first getting out of bed after surgery, and time of first eating after surgery, including light drink. Discussion This is the first randomized controlled trial to compare the impacts of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. If a favorable effect and safety of gasless vNOTES for hemodynamic profiles and outcomes in patients are shown, gasless vNOTES would be an optimal treatment option for patients with benign gynecological disease. Trial registration The trial was registered at https://www.chictr.org.cn/showproj.html?proj=182441 with registration No. ChiCTR2200064779 on Oct 17, 2022.

Abstract Background Diabetic encephalopathy (DE) is a complication of diabetes that leads to cognitive and behavioral decline. Utilizing safe and effective complementary and alternative medications for its management is a wise choice. Previous studies have shown that GuanXinNing Tablet (GXNT), an oral preparation primarily derived from two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., exerts a beneficial neuroprotective effect. In this study, we explored the protective effects of GXNT on DE in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet, aiming to ascertain its significance and potential mechanisms. Methods ZDF rats were induced to develop type 2 diabetes (T2DM) with DE by a high-fat diet and treated with GXNT for 8 weeks until they were 20 weeks old. Throughout the experiment, the animals’ vital parameters, such as body weight, were continuously monitored. Cognitive function was evaluated using the Y maze test. Biochemical kits were employed to analyze blood glucose, lipids, and vascular endothelial-related factors. Cerebrovascular lesions were assessed using magnetic resonance angiography (MRA) imaging. Brain lesions were evaluated using hematoxylin and eosin (H&E) staining and ultrastructure observation. IgG and albumin (ALB) leakage were detected using immunofluorescence. Results GXNT demonstrated an enhancement in the overall well-being of the animals. It notably improved cognitive and behavioral abilities, as demonstrated by extended retention time in the novel heterogeneous arm during the Y-maze test. GXNT effectively regulated glucose and lipid metabolism, reducing fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), and total cholesterol (TC) levels. Additionally, it exhibited a protective effect on the vascular endothelium by reducing the serum TXB2/PGI2 ratio while elevating NO and PGI2 levels. Moreover, GXNT ameliorated stenosis and occlusion in cerebral vessel branches, increased the number of microvessels and neurons around the hippocampus, and improved microvascular occlusion in the cerebral cortex, along with addressing perivascular cell abnormalities. Immunofluorescence staining showed a decrease in the fluorescence intensity of IgG and ALB in the cerebral cortex. Conclusions GXNT demonstrated a highly satisfactory protective effect on DE in ZDF rats. Its mechanism of action could be based on the regulation of glucolipid metabolism and its protective effect on the vascular endothelium.

ObjectiveTo explore the medical significance of methylated septin9 (mSEPT9) in monitoring recurrence and prognostic assessment in individuals with surgically treated colorectal cancer (CRC).MethodsTo investigate the role of Septin9 in colorectal cancer, we utilized the TIMER2.0 database to analyze its differential expression between tumor tissues and adjacent normal tissues. Colorectal cancer RNA-seq data from the TCGA database was downloaded and curated. The clinical relevance of mSEPT9 in colorectal cancer was explored by examining the correlation between Septin9 methylation levels and clinical characteristics using UALCAN and MethSurv software. Peripheral blood samples were obtained from 130 CRC subjects who underwent surgery for the detection of mSEPT9 and carcinoembryonic antigen (CEA) expression, along with collection of clinicopathological data such as age, gender, tumor site, TNM stage, and tumor differentiation. Patients were followed up for at least 3 years post-surgery until the death or final follow-up dates (31/12/2022). Additionally, peripheral blood samples were collected from 30 colorectal cancer surgery patients for mSEPT9 detection before and 7 days after surgery.ResultsThrough bioinformatic database analysis, we identified higher expression levels of SEPT9 mRNA in most tumor tissues compared to normal tissues. Similarly, both paired and unpaired CRC tissues exhibited elevated expression of Septin9 when compared to normal tissues. Following GO and KEGG analysis of Septin9 target genes, we discovered their significant associations with ncRNA metabolic processes, ribonucleoprotein complex biogenesis, spliceosomes, and viral carcinogenesis. Furthermore, the overexpression of mSeptin9 was observed in CRC tissues, and it demonstrated a correlation with colon cancer staging and histologic classification. In our clinical sample study, The positive rate of mSEPT9 in CRC patients 7 days after surgery was 43.44% lower than that of preoperative. The differences in TNM stage, tumor differentiation degree, and preoperative CEA expression level between the preoperative mSEPT9 positive and negative groups of CRC were statistically significant (P < 0.05). Recurrence free survival (RFS) and overall survival (OS) were shorter in the preoperative mSEPT9-positive group, meaning preoperative mSEPT9 status was a risk factor for CRC recurrence and prognosis (P < 0.05). The sensitivity, specificity, and AUC value of preoperative mSEPT9 and CEA levels for predicting postoperative recurrence in CRC patients were 88% vs. 72%, 56.19% vs. 55.24%, and 0.721 vs. 0.636 respectively, well the AUC value of the combined prediction of postoperative recurrence was 0.758.ConclusionThe detection of mSEPT9 combined with CEA in preoperative plasma helps predict recurrence in colorectal cancer patients.

This paper evaluates the carbon dioxide sequestration potential in the saline aquifers of the South Qiongdongnan–Yinggehai Basin. By using a hierarchical evaluation method, the assessment is divided into five stages: the basin level, the zone level, the target level, the site level, and the injection level. The study primarily focuses on evaluating the sequestration potential of and identifying favorable zones of saline aquifers at the basin and zone levels. The optimized volumetric method is adopted, based on the integration of multi-source data such as regional geological maps, seismic data, core porosity, and permeability. The results show that the estimated potential of the Yinggehai Basin is 60.6 billion tons at the basin level and 54.6 billion tons at the zone level. Additionally, the estimated potential of the South Qiongdongnan Basin is 261.5 billion tons at the basin level and 234.8 billion tons at the zone level. The suitability evaluation indicates that the Yinggehai Basin is moderately suitable overall, the northern depression of the South Qiongdongnan Basin is suitable, the central uplift is moderately suitable, and the central depression is not suitable. This study provides a scientific foundation for carbon dioxide sequestration in marine basins and introduces novel ideas and methods for future similar research. This is highly significant for subsequent engineering applications and decision-making processes.

Background: Evidence-based venous thromboembolism prevention and management is a priority for global health services. Low adoption of venous thromboembolism guidelines can result in compromised patient outcomes. Understanding clinicians' and patients' perceptions of barriers to and facilitators for guideline implementation and mapping identified barriers and facilitators to the Consolidated Framework for Implementation Research may inform theoretical interventions to improve guideline adoption rates. Objective: To synthesize quantitative and qualitative evidence on both 1) perceptions and experiences of hospital clinicians and patients regarding venous thromboembolism practices and 2) barriers to and facilitators for guideline implementation. Data source: English-language studies from MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane published between 2012 and 2023. Methods: The included studies primarily focused on two aspects: firstly, elucidating the perceptions and experiences of healthcare providers and patients concerning venous thromboembolism management practices, and secondly, identifying the barriers and facilitators that influence the implementation of venous thromboembolism guidelines. The Mixed Methods Appraisal Tool was used for critical appraisal. Quantitative data were transformed into qualitized data and then thematically synthesized with qualitative data to compare the perspectives of clinicians and patients. Barriers and facilitators related to each topic were mapped to the Consolidated Framework for Implementation Research, and the barriers were entered into its implementation strategy matching tool to obtain implementation strategies. Results: Of 8262 studies of varying quality, 26 (20 quantitative, five qualitative, and one mixed-methods) met the inclusion criteria. Four themes represented factors influencing guideline implementation: 1) healthcare-led multidisciplinary prevention and management, 2) feasibility of guideline implementation, 3) patient involvement in prevention and management, and 4) government and hospital environments and related systems. The majority of barriers identified by healthcare providers were related to the second and fourth themes, while for patients, there were multiple barriers under the third theme. Barriers were mainly mapped into four domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. Most facilitators mentioned by healthcare providers and patients were related to themes 1, 3, and 4 and mapped to three domains: outer setting, inner setting, and characteristics of individuals. Seven optimal implementation strategies were obtained through the Consolidated Framework for Implementation Research-Expert Recommendations for Implementing Change matching tool. Conclusions: We highlighted the most influential factors associated with implementing venous thromboembolism guidelines from the perspectives of both clinicians and patients, and mapping these factors to the Consolidated Framework for Implementation Research can help to develop stakeholder-appropriate implementation interventions. Registration: This study's protocol has been registered at PROSPERO under the registration number CRD42024518184.

Aims/Introduction: Diabetic kidney disease (DKD) is defined as diabetes with impaired renal function, elevated urinary albumin excretion, or both. DKD is one of the most common microvascular complications of diabetes and plays an important role in the cause of end-stage renal disease (ESRD). About 5% of people with type 2 diabetes (T2DM) already have kidney damage at the time they are diagnosed, but other triggers of renal insufficiency, such as obesity, hyperlipidemia, glomerular atherosclerosis are often present, making it difficult to define “diabetic kidney disease” or “diabetic nephropathy” precisely in epidemiology or clinical practice. Therefore, the aim of this study is to identify diabetic patients with CKD at an early stage, and evaluate the value of tubular injury markers including α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), N-acetyl-beta-D-glucosaminidase (NAG) and Urinary retinol binding protein (URBP) in the development of diabetes to DKD.Materials and methods: We recruited a total of 182 hospitalized patients with T2DM in the First Affiliated Hospital of Zhengzhou University from February 2018 to April 2023. We collected basic clinical characteristics and laboratory biochemical parameters of the patients. Based on their levels of urinary albumin creatinine ratio (UACR) and glomerular filtration rate (GFR), patients were divided into DM group (UACR≤30 mg/g and eGFR≥90 mL/min/1.73 m2, n = 63) and DKD group (UACR>30 mg/g or eGFR

The electronic structure of two-dimensional (2D) materials in van der Waals heterojunctions also appears extensive theoretical research, we use DFT-D2 theory to calculate the energy band, density of states, formation energy, work function, charge density difference, optical properties, and our theoretical calculations show that there is no electrons and holes redistribution at the intrinsic ZnO composite graphene interface, ZnO vacancy defects and doping not only make electron–hole good separation, but also a significant increase in the UV absorption intensity and range. We analyze the effects of the electron–hole pair separation at the heterogeneous junction interface by combining the work function and the movement of the Dirac point. We found that when defected ZnO composite graphene, there is the maximum formation energy, the value is 5.4eV,the largest moving distance of the Fermi level, 0.73eV, and the maximum absorption strength and range of UV light. This 2D van der Waals heterojunction provides a promising prospect for electrons, photovoltaic, solar cell.

Grain legumes play a significant global role and are integral to agriculture and food production worldwide. Therefore, comprehending and analyzing the factors that influence grain legume yield are of paramount importance for guiding agricultural management and decision making. Traditional statistical analysis methods present limitations in interpreting results, but explainable artificial intelligence (AI) provides a visual representation of model results, offering insights into the key factors affecting grain legume yield. In this study, nine typical grain legume species were selected from a published global experimental dataset: garden pea (Pisum sativum), chickpea (Cicer arietinum), cowpea (Vigna unguiculata), garden vetch (Vicia sativa), faba bean (Vicia faba), lentil (Lens culinaris), pigeon pea (Cajanus cajan), peanut (Arachis hypogaea), and white lupine (Lupinus albus). Seven commonly used models were constructed for each legume species, and model performance evaluation was conducted using accuracy, AUC, recall, precision, and F1 score metrics. The best classification model was selected for each grain legume species. Employing Decision Tree analysis, Feature Importance Evaluation, and SHapley Additive exPlanations (SHAP) as explainable techniques, our study conducted both individual and comprehensive analyses of nine leguminous crops. This approach offers a novel perspective, unveiling not only the unique responses of each crop to the influencing factors but also demonstrating the common factors across different crops. According to the experimental results, XGboost (XGB) and Random Forests (RF) are the best-performing models among the nine types of grain legumes, and the classification accuracy of a specific species is as high as 87.33%. Insights drawn from the feature importance map reveal that several factors, including aerial biomass, precipitation, sunshine duration, soil conditions, growth cycle, and fertilization strategy, have a pivotal influence. However, it was found from the SHAP graph that the responses of various crops to these factors are not the same. This research furnishes novel perspectives and insights into understanding the factors influencing grain legume yields. The findings provide a robust scientific foundation for agricultural managers, experts, and policymakers in the pursuit of optimizing pulse yields and advancing agricultural sustainability.

Glycolate plays an important role as a platform chemical in both polymeric material and cosmetic industries. However, the microbial production of glycolate often encounters challenges associated with unbalanced metabolic flux, leading to a notably low titer. Additionally, the use of expensive inducers, such as IPTG, contributes to an increase in the overall production cost. To address these issues, the key enzymes involved in the glycolate biosynthetic route, including citrate synthase (gltA), isocitrate lyase (aceA), isocitrate dehydrogenase kinase/phosphatase (aceK) and glyoxylate reductase (ycdW), were overexpressed in E. coli under the control of inducible promoters with varying strengths in order to determine the optimal combination. Subsequently, the glycolate pathway was further modulated by replacing inducible promoters with various constitutive synthetic promoters. Through this systematic optimization, the best strain, named Mgly4T1562, produced 3.02 g/L glycolate with 97.32% theoretical yield in shake-flask cultivation. The titer further increased to 15.53 g/L in a fed-batch experiment. Notably, this study marks the first successful utilization of synthetic promoters in tuning the glycolate biosynthetic pathway for glycolate biosynthesis. The strategy presented in this research holds significant promise for facilitating the cost-effective and industrially viable production of glycolate without the need for expensive inducers.

The energy transfer process occurred at all stages of the production system and could demonstrate potential changes in the state of the system during production. The cut tobacco production process also would require a large amount of heat energy to make a high-quality product. Based on the energy balance analysis of the SH626 dryer, the energy consumption of the tobacco drying process was the highest unit, which accounts for approximately 60% of the energy consumption of the whole tobacco production process. The energy transfer efficiency of the sheet heating system was only 0.46 ∼ 0.58 and was mainly influenced by the working temperature of thin plates. The energy transfer efficiency of the hot air heating system was 0.24 ∼ 0.33 and was influenced by the hot air mass flow rate. The energy transfer system remained low levels of energy transfer efficiency and had great potential for saving energy. Those conclusions of this study could provide a theoretical basis to improve dryer system energy transfer efficiency by the thermal integrated system and the intelligent control system.

Objectives To compare the prognostic values of three lymph node staging systems in renal cell carcinoma (RCC), including the number of positive lymph nodes (NPLN), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS).Design A retrospective cohort study using data from the Surveillance, Epidemiology and End Results (SEER) database.Setting and participants 1904 patients with pathological N1 RCC, diagnosed from 2004 to 2015 and underwent nephrectomy combined with lymph node dissection, were identified from the SEER database.Primary outcome measure The primary outcome of this study was overall survival (OS). Restricted cubic spline functions and multivariable Cox regression analyses were employed to characterise the associations of OS with NPLN, LNR and LODDS, respectively.Results Data of 1904 eligible RCC patients were extracted from the SEER database. The mortality risks of RCC patients increased with the increasing of NPLN, LNR and LODDS. NPLN (NPLN3 vs NPLN1, HR 1.22, 95% CI 1.05 to 1.43, p=0.001), LNR (LNR3 vs LNR1, HR 1.46, 95% CI 1.28 to 1.67, p

Objective: To observe the effects of Lingguizhugan decoction on obesity and investigate its preliminary mechanism in activating fat mobilization based on gut microbiota. Methods: In this prospective one-armed clinical research, we analyzed the data of 32 obese patients with Yang deficiency and phlegm-dampness syndrome treated by Lingguizhugan decoction combined with lifestyle intervention for 2 months. The anthropometric data, body composition, metabolic data, traditional Chinese medicine (TCM) syndrome scores, fecal 16S rDNA, core temperature, and visceral fat fractions of patients were analyzed. Animal experiments were conducted for further verification: ob/ob mice and pseudo-germ-free ob/ob mice (ABX) were given Lingguizhugan decoction by gavage for 2 months. The body mass, core temperature (rectum), respiratory exchange ratio (RER), micro-positron emission tomography/computed tomography (micro-PET/CT) results, and uncoupling protein 1 (UCP1) expression (including gene, protein, and immunohistochemistry staining results) in inguinal adipose tissue of mice were evaluated. Results: The clinical effective rates of TCM and Western medicine were 96.87% and 93.75%, respectively. Compared with those before treatment, the body mass index (BMI), body fat ratio (BFR), waist-to-hip ratio, TCM syndrome scores, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2hPPG), glycosylated hemoglobin A1C (GHbA1c), and blood uric acid (UA) significantly decreased after treatment. Moreover, we randomly selected five patients to investigate their core temperature and visceral fat fractions. Compared with healthy volunteers, the five patients had higher core temperature. According to the 1.5 T magnetic resonance imaging (MRI) results, the fat fractions of the liver, pancreas, greater omentum, and subcutaneous abdominal wall were notably decreased after treatment. Fecal 16S rDNA principal component analysis and partial least squares discriminant analysis showed that the biodiversity and species abundance of gut microbiota were significantly different between pre- and post-treatment. The relative abundance of Bacteroidetes was remarkably elevated and that of Firmicutes was notably reduced by Lingguizhugan decoction. The animal experiments showed that the weight of ob/ob mice decreased significantly by gavage of Lingguizhugan decoction for 2 months. Compared with the model group, the Lingguizhugan group showed increased core temperature (rectum) and decreased RER. Micro-PET/CT showed that 18F-2-deoxyglucose-6-phosphate (18F-FDG) was enriched obviously and the SUV index was increased in the Lingguizhugan group. However, after eliminating the gut microbiota in the ABX group, the weight loss, core temperature, 18F-FDG enrichment, and SUV index decreased, and RER was similar to that in the model group despite simultaneous treatment with Lingguizhugan decoction. According to the gene, protein, and immunohistochemistry results UCP1 expression in inguinal adipose tissue of mice in the Lingguizhugan decoction group was significantly higher than that in the model group. However, UCP1 expression in the ABX group was downregulated after eliminating the gut microbiota. Conclusion: Lingguizhugan decoction combined with lifestyle intervention effectively improved the BMI, BFR, glucolipid metabolism, and TCM syndrome scores of obese patients with Yang deficiency and phlegm-dampness syndrome. We infer that the mechanism of Lingguizhugan decoction in promoting fat mobilization may lie in the browning of white adipose tissue (WAT) triggered by gut microbiota. Further animal experiments indicated that Lingguizhugan decoction promoted the browning of WAT and activation of fat mobilization by gut microbiota.

Atherosclerosis is a chronic progressive inflammatory disease of the large and medium-sized artery walls. The molecular mechanisms regulating the onset and progression of atherosclerosis remain unclear. T cells, one of the most common immune cell types in atherosclerotic plaques, are increasingly recognized as a key mediator in the pathogenesis of atherosclerosis. Th1 cells are a subset of CD4+ T helper cells of the adaptive immune system, characterized by the expression of the transcription factor T-bet and secretion of cytokines such as IFN-γ. Converging evidence shows that Th1 cells play a key role in the onset and progression of atherosclerosis. Besides, Th1 is the central mediator to orchestrate the adaptive immune system. In this review, we aim to summarize the complex role of Th1 cells in atherosclerosis and propose novel preventative and therapeutic approaches targeting Th1 cell-associated specific cytokines and receptors to prevent atherogenesis.

BackgroundImmunoglobulin A nephropathy (IgAN) is a highly prevalent glomerular disease. The diagnosis potential of the gut microbiome in IgAN has not been fully evaluated. Gut microbiota, serum metabolites, and clinical phenotype help to further deepen the understanding of IgAN.Patients and methodsCohort studies were conducted in healthy controls (HC), patients of IgA nephropathy (IgAN) and non-IgA nephropathy (n_IgAN). We used 16S rRNA to measure bacterial flora and non-targeted analysis methods to measure metabolomics; we then compared the differences in the gut microbiota between each group. The random forest method was used to explore the non-invasive diagnostic value of the gut microbiome in IgAN. We also compared serum metabolites and analyzed their correlation with the gut microbiome.ResultsThe richness and diversity of gut microbiota were significantly different among IgAN, n_IgAN and HC patients. Using a random approach, we constructed the diagnosis model and analysed the differentiation between IgAN and n_IgAN based on gut microbiota. The area under the receiver operating characteristic curve for the diagnosis was 0.9899. The metabolic analysis showed that IgAN patients had significant metabolic differences compared with HCs. In IgAN, catechol, l-tryptophan, (1H-Indol-3-yl)-N-methylmethanamine, and pimelic acid were found to be enriched. In the correlation analysis, l-tryptophan, blood urea nitrogen and Eubacterium coprostanoligenes were positively correlated with each other.ConclusionOur study demonstrated changes in the gut microbiota and established models for the non-invasive diagnosis of IgAN from HC and n_IgAN. We further demonstrated a close correlation between the gut flora, metabolites, and clinical phenotypes of IgAN. These findings provide further directions and clues in the study of the mechanism of IgAN.

Abstract Aim To investigate the relationship between pressure ulcers risk and severity of obstructive coronary artery disease (CAD) by invasive coronary angiography. Design Cross‐sectional study. Methods A total of 193 consecutive patients with underlying pressure ulcers risk who underwent invasive coronary angiography were enrolled. Subjects were divided into three groups according to severity of coronary artery stenosis. Pressure ulcers risk score, fall risk score, self‐care ability score and cardiovascular risk factors were compared among the three groups. Multivariate regression analysis and receiver operating curve analysis were performed to explore the diagnostic value of Braden score for left main or three‐vessel disease. Results Patients with more severe CAD had higher pressure ulcers risk. The percentage of high‐pressure ulcers risk was highest in left main or three‐vessel disease group, compared with control group and single‐ or two‐vessel disease group. After adjusting for age, body mass index, diabetes, chronic kidney disease and other confounding factors, Braden score was an independent predictor of left main or three‐vessel disease. Moreover, higher Braden score had a moderate area under the curve for excluding more severe CAD. In conclusion, among patients planning for coronary angiography, pressure ulcers risk assessment is conducive to predict the severity of obstructive CAD.

Summary: Purpose: To investigate the effectiveness of a structured death education program for older adults with chronic illness and their family caregivers. Methods: This study adopted two-group, nonrandomized quasi-experimental design. Patient–caregiver dyads in the intervention group (N = 40 dyads) engaged in the death education program at the bedside once a week for 5 weeks, and were compared with participants (N = 40 dyads) in the control group who received usual health education. The program consisted of five sessions based on the Interaction Model of Client Health Behavior. Death attitude, death competence, well-being, family function, and satisfaction were measured at baseline (T0), immediately after the intervention (T1), and 1 month later (T2). Data collection was conducted from July 30, 2019, to December 30, 2019. Results: The intention-to-treat analysis The intention-to-treat analysis of between groups at 1-month follow-up revealed that the intervention group had greater decreases in the fear of death (p=.002, 95% CI -2.53, -0.47; p

Abstract Background Physical activity (PA) is low among elderly residents in nursing homes in China. We aimed to determine the factors that influence PA among elderly nursing home residents and their direct or indirect effects on PA levels. Methods The PA levels of the participants were measured using the International Physical Activity Questionnaire, and their health beliefs were assessed using a self-developed 18-item questionnaire titled the ‘Health Beliefs of Nursing Home Residents Regarding Physical Activity’ in accordance with Health Belief Model (HBM) constructs. The correlations between HBM constructs and PA levels were analyzed and a regression-based path analysis was conducted to examine the relationships between HBM constructs and PA levels. Results A total of 180 residents with a mean age of 82.5 years (standard deviation = 5.76) were recruited. Linear regression analysis revealed that self-efficacy (p

Abstract Background Atherosclerosis is a major contributor to cardiovascular events, however, its molecular mechanism remains poorly known. Animal models of atherosclerosis can be a valuable tool to provide insights into the etiology, pathophysiology, and complications of atherosclerosis. In particular, Tibetan minipigs are a feasible model for studying diet-related metabolic and atherosclerotic diseases. Methods We used vascular transcriptomics to identify differentially expressed genes (DEGs) in high fat/cholesterol (HFC) diet-fed Tibetan minipig atherosclerosis models, analyzed the DEGs gene ontology (GO) terms, pathways and protein-protein interactions (PPI) networks, and identified hub genes and key modules using molecular complex detection (MCODE), Centiscape and CytoHubba plugin. The identified genes were validated using the human carotid atherosclerosis database (GSEA 43292) and RT-PCR methods. Results Our results showed that minipigs displayed obvious dyslipidemia, oxidative stress, inflammatory response, atherosclerotic plaques, as well as increased low-density lipoprotein (LDL) and leukocyte recruitment after 24 weeks of HFC diet feeding compared to those under a regular diet. Our RNA-seq results revealed 1716 DEGs in the atherosclerotic/NC group, of which 1468 genes were up-regulated and 248 genes were down-regulated. Functional enrichment analysis of DEGs showed that the HFC diet-induced changes are related to vascular immune-inflammatory responses, lipid metabolism and muscle contraction, indicating that hypercholesterolemia caused by HFC diet can activate innate and adaptive immune responses to drive atherosclerosis development. Furthermore, we identified four modules from the major PPI network, which are implicated in cell chemotaxis, myeloid leukocyte activation, cytokine production, and lymphocyte activation. Fifteen hub genes were discovered, including TNF, PTPRC, ITGB2, ITGAM, VCAM1, CXCR4, TYROBP, TLR4, LCP2, C5AR1, CD86, MMP9, PTPN6, C3, and CXCL10, as well as two transcription factors (TF), i.e. NF-ĸB1 and SPI1. These results are consistent with the expression patterns in human carotid plaque and were validated by RT-PCR. Conclusions The identified DEGs and their enriched pathways provide references for the development and progression mechanism of Tibetan minipig atherosclerosis model induced by the HFC diet.

Coronary atherosclerosis (CA) is a chronic and evolving inflammatory disease characterized by the build-up of atherosclerotic plaque in the wall of coronary arteries. Guanxinning tablet (GXNT) is a novel Chinese medicine formula, which has been clinically used to treat coronary heart disease for many years. However, the potential mechanism for treating CA remains unclear. Thus, the study was aimed at investigating the therapeutic effect of GXNT on CA and further explore the underlying mechanisms from the perspective of gut microbiota. Following the establishment of a CA model in Tibetan minipigs, GXNT was orally administrated. We simultaneously detected blood lipid levels, observed ventricular function using ultrasound examination, measured platelet aggregation, and checked changes in inflammatory factors, oxidative stress factors, and vascular endothelial injury-related indexes applying ELISA assays. Histopathological changes of coronary artery tissue were subsequently evaluated using Sudan IV staining, HE staining, Oil red “O” staining, and immunohistochemistry assays. Finally, alterations of the gut microbiota and microbial metabolites were detected using metagenomic sequencing and targeted metabolomics, respectively. The results have suggested that GXNT could regulate dyslipidemia, improve heart function, and inhibit the levels of ox-LDL, CRP, TNF-α, IL-1β, SOD, MDA, vWF, and ET-1, as well as platelet aggregation. Additionally, histopathological findings revealed that GXNT could reduce lipid deposition, alleviate AS lesions, and restrain the expressions of NF-κB, TNF-α, and MMP-9. Furthermore, the composition of the gut microbiota was altered. Specifically, GXNT could upregulate the relative abundance of Prevotellaceae and Prevotella and downregulate the abundance of Proteobacteria, Enterobacteriaceae, and Escherichia. As for microbial metabolites, GXNT could increase fecal propionic acid, butyric acid, and LCA-3S and decrease fecal TMA-related metabolites, CDCA, and serum TMAO. In sum, the results showed that GXNT had a satisfactory anti-CA effect, and the mechanism was closely associated with modulating gut microbiota and related metabolites.

Abstract Objective Hepatocellular carcinima is one of the most common tumors in clinic and also one of the leading causes of death from cancer worldwide. Quercetin shows significant effects on blocking the development of various cancers. Methods We used the human hepatocellular carcinoma LM3 and nude mice tumor model to assess the effects of quercetin in hepatocellular carcinoma and clarify its mechanism of action. We collected LM3 cell line treated with different doses of quercetin at different time periods and determined the vital indexes. The liver tissues of mice were collected and used for western boltting (WB), Hematoxylin and Eosin (H&E) and TUNEL staining. Results Results indicated that quercetin suppressed the Hepatocellular carcinoma (HCC) growth both in vivo and in vitro. Quercetin could disturb LM3 cells proliferation and cell cycle distribution, thus inducing apoptosis. At the same time, quercetin inhibited LM3 cells migration and invasion and promoted HCC autophagy. These effects at least partly depended on the down‐regulation of the activation of JAK2 and STAT3 by quercetin. Conclusion Quercetin inhibited hepatocellular carcinoma progression by modulating cell apoptosis, migration, invasion, and autophagy; and its effects were at least partly related with the JAK2/STAT3 signaling pathway.

Abstract Background The treatment for advanced primary hepatocellular carcinoma (HCC) is sorafenib (SORA), while HCC has become increasingly drug resistant with enhanced aerobic glycolysis. The present study aimed to examine the chemotherapeutic effects of a flavonoid proanthocyanidin B2 (PB2) on HCC. Methods Five kinds of HCC cell lines and LO2 were used to test the effect of PB2 on aerobic glycolysis. The proliferation, cell cycle, apoptosis and a xenograft mouse model were analyzed. Lentivirus overexpressed pyruvate kinase M2 (PKM2) or sh-PKM2 was used to verify the target of PB2. The detailed mechanism was investigated by immunofluorescence, co-immunoprecipitation, and western blotting. Results PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro. PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2. In addition, PKM2 inhibited the nuclear translocation of PKM2 and co-localization of PKM2/HIF-1α in the nucleus, leading to the inhibition of aerobic glycolysis. Co-treatment with PB2 was also effective in enhancing the chemosensitivity of SORA. Conclusions PB2 inhibited the expression and nuclear translocation of PKM2, therefore disrupting the interaction between PKM2/HSP90/HIF-1α, to suppress aerobic glycolysis and proliferation, and trigger apoptosis in HCC via HIF-1α-mediated transcription suppression.

Overuse of carbapenems has led to the increasing carbapenem-resistant Enterobacteriaceae. It is still unknown whether other antibiotics [especially novel β-lactam/β-lactamase inhibitor combinations (BL/BLIs)] are better than carbapenems in the treatment of Enterobacteriaceae. A systematic literature search was performed to identify randomized controlled trials (RCTs) assessing the efficacy and safety of any antibiotics on Enterobacteriaceae infections. We carried out a traditional paired meta-analysis to compare ceftazidime/avibactam to comparators. Network meta-analysis (NMA) was conducted to integrate direct and indirect evidence of all interventions. Moreover, cost-effectiveness analysis using a combined decision analytical Markov model was completed for the treatment of patients with complex urinary tract infection (cUTI). A total of 25 relevant RCTs were identified, comprising 15 different interventions. Ceftazidime/avibactam exhibited comparable efficacy and safety with comparators (carbapenems) in the paired meta-analysis. In the NMA, the surface under the cumulative ranking curve probabilities showed that in terms of efficacy, the interventions with the highest-ranking were meropenem/vaborbactam, meropenem, imipenem/cilastatin, ceftriaxone, ceftazidime/avibactam, and ceftolozane/tazobactam [but no significant difference between any two antibiotics (p > 0.05)]. Regarding safety, ceftazidime/avibactam had a higher incidence of adverse events than that of piperacillin/tazobactam (relative risk = 0.74, 95% confidence interval = 0.59–0.94). Based on drug and hospitalization costs in China, the incremental cost-effectiveness ratio per quality-adjusted life-year gained in the patients with cUTI for meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam compared to imipenem/cilastatin were US$579, US$24569, and US$29040, respectively. The role of these BL/BLIs to serve as alternatives to carbapenems requires large-scale and high-quality studies to validate.

The dosage regimen of vancomycin, teicoplanin and daptomycin remains controversial for critically ill patients undergoing continuous renal replacement therapy (CRRT). Monte Carlo simulation was applied to identify the optimal regimens of antimicrobial agents in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections based on the mechanisms of different CRRT modalities on drug clearance. The optimal vancomycin dosage for patients received a CRRT doses ≤ 30 mL/kg/h was 20 mg/kg loading dose followed by 500 mg every 8 h, while 1 g every 12 h was appropriate when 35 mL/kg/h was prescribed. The optimal teicoplanin dosage under a CRRT dose ≤ 25 mL/kg/h was four loading doses of 10 mg/kg every 12 h followed by 10 mg/kg every 48 h, 8 mg/kg every 24 h and 6 mg/kg every 24 h for continuous veno-venous hemofiltration, continuous veno-venous hemodialysis and continuous veno-venous hemodiafiltration, respectively. When the CRRT dose increased to 30–35 mL/kg/h, the teicoplanin dosage should be increased by 30%. The recommended regimen for daptomycin was 6–8 mg/kg every 24 h under a CRRT dose ≤ 25 mL/kg/h, while 8–10 mg/kg every 24 h was optimal under 30–35 mg/kg/h. The CRRT dose has an impact on probability of target attainment and CRRT modality only influences teicoplanin.

Creep generally showed a great impact on the temperature stress of concrete structure. At present, little research has been done on the creep law of cemented sand and gravel (CSG), and the calculation of creep temperature stress mainly adopts a set of relevant parameters. In this context, experimental compressive creep tests were carried out on the specimens of large-sized cylinders with different cementing agent contents; the creep temperature stress of CSG was also calculated. The results showed that the creep of CSG increased with the increase of cementing agent content, but the specific creep was not obvious. In addition, the creep model of CSG with high accuracy was also obtained, which could provide a basis for the numerical simulation of CSG dam. Furthermore, the results of numerical simulation showed that creep has a great influence on the stress of CSG dam, and the thermal stress energy was less than 37%. At the same time, it was necessary to determine whether temperature control should be considered according to different cementing agent content and external climate conditions, which cannot be generalized.

Densities of sodium arsenite (NaAsO2) aqueous solution with the molality varied from 0.19570 to 1.94236 mol·kg−1 at temperature intervals of 5 K from 283.15 to 363.15 K and 101 ± 5 kPa were measured by a precise Anton Paar Digital vibrating-tube densimeter. Apparent molar volumes (VΦ) and thermal expansion coefficient (α) were obtained on the basis of experimental data. The 3D diagram of apparent molar volume against temperature and molality and the diagram of thermal expansion coefficient against molality were generated. According to the Pitzer ion-interaction equation of the apparent molar volume model, the Pitzer single-salt parameters (βM,X0υ, βM,X1υ, βM,X2υ, and CM,Xυ, MX = NaAsO2) and their temperature-dependent correlation F(i, p, T) = a1 + a2ln (T/298.15) + a3(T − 298.15) + a4/(620 − T) + a5/(T − 227) (where T is temperature in Kelvin and ai are the correlation coefficients) for NaAsO2 were obtained for the first time. The predictive apparent molar volumes agree well with the experimental values, and those results indicated that the single-salt parameters and the temperature-dependent formula are reliable.

The optimal regimens of novel β-lactam/β-lactamase inhibitors (BLBLIs), ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam, are not well defined in critically ill patients. This study was conducted to identify optimal regimens of BLBLIs in these patients. A Monte Carlo simulation was performed using the published data to calculate the joint probability of target attainment (PTA) and the cumulative fraction of response (CFR). For the target of β-lactam of 100% time with free drug concentration remains above minimal inhibitory concentrations, the PTAs of BLBLIs standard regimens were Enterobacteriaceae and Pseudomonas aeruginosa. For ceftazidime/avibactam, 2000 mg/500 mg/8 h by 4 h infusion achieved >90% CFR for Escherichia coli; even for 4000 mg/1000 mg/6 h by continuous infusion, CFR for Klebsiella pneumoniae was Pseudomonas aeruginosa. For ceftolozane/tazobactam, the CFR of standard regimen was >90% for Escherichia coli, however, 2000 mg/1000 mg/6 h by continuous infusion achieved Klebsiella pneumoniae and Pseudomonas aeruginosa. For meropenem/vaborbactam, standard regimen achieved optimal attainments for Escherichia coli and Klebsiella pneumoniae; 2000 mg/2000 mg/6 h by 5 h infusion, 2500 mg /2500 mg/6 h by 4 h infusion, 3000 mg/3000 mg/6 h by 3 h infusion and 4000 mg/4000 mg/8 h by 5 h infusion achieved >90% CFRs for Pseudomonas aeruginosa. The CFRs of three BLBLIs were similar for Escherichia coli, but meropenem/vaborbactam were superior for Klebsiella pneumoniae and Pseudomonas aeruginosa.

Low birth-weight (LBW) neonates exhibit a lower growth rate and impaired intestinal development. However, the reasons for abnormal development of small intestine in LBW piglets have not been widely studied. The present study focused on the redox status and mitochondrial morphology and functions of the small intestine in LBW newborn piglets. Ten newborn normal birth-weight (NBW) piglets and LBW piglets from 10 primiparous sows with the same parturition day were selected and sampled immediately without sucking colostrum. The small intestine tissues were collected and measured. Compared with NBW newborn piglets, LBW newborn piglets had a significantly decreased length and weight of the small intestine (p < 0.05) as well as the villus height/crypt depth (V/C) index in the jejunum (p < 0.05). Furthermore, LBW piglets had a lower gene expression of tight junction protein zonula occluden-1 (ZO1), claudin 1, antioxidant enzyme catalase (CAT), glutathione peroxidase (GPX) and heme oxygenase-1 (HO-1) in jejunum (p < 0.05). Meanwhile, LBW induced mitochondrial vacuolation and significantly decreased the mRNA expression of PPARγ coactivator-1α (PGC-1α) (p < 0.05) and tended to decrease the expression of cytochrome coxidase IV (Ccox IV) (p = 0.07) and cytochrome C (Cytc) (p = 0.08). In conclusion, LBW newborn piglets showed an abnormal development of the small intestine and disturbed redox status, and this may be caused by impaired morphology and the functions of mitochondria in the jejunum.

Hepatic ischemia reperfusion (IR) injury (IRI) occurs during liver transplantation, hepatectomy, and hemorrhagic shock. Oleanolic acid (OA) is a natural compound with antioxidant and anti-inflammatory activity that has been used to treat liver disorders in clinical practice for several years. Here, we investigated the effects and underlying mechanisms of OA in hepatic IRI. A 60-minute partial (70%) hepatic, warm, ischemic reperfusion model was established in BALB/c mice, and two doses (30 and 60 mg/kg) of OA were administered intragastrically for 7 consecutive days prior to hepatic IR. Orbital blood and liver specimens were collected at 2, 8, and 24 h after IR. The results showed that OA preconditioning significantly alleviated hepatic injury, as evidenced by decreased alanine aminotransferase and aspartate aminotransferase levels; improved histology, inhibition of JNK phosphorylation, and high mobility group box 1 (HMGB1); and tumor necrosis factor-α downregulation in hepatic IR mice. OA upregulated Bcl-2 and downregulated caspase-3, caspase-9, Bax, Beclin 1, and LC3, which play crucial roles in the regulation of apoptosis and autophagy. These findings highlighted the protective effects of OA against hepatic IRI mediated by the inhibition of apoptosis and autophagy and the release of HMGB1, which acted as a late inflammatory mediator in hepatic IRI.

Salvianolic acid A (SAA), an important bioactive polyphenolic acid found in Salvia miltiorrhiza Bunge, may be used for treating metabolic disorders due to its anti-inflammatory activity. Since chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM) complicated with atherosclerosis (AS), SAA may have beneficial effects on AS. Here, we evaluated the effects of SAA on metabolic disorders in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet and Vitamin D3 injections. Compared with the model group, the SAA high dosage (1 mg/kg) group exhibited decreased hemoglobin A1C levels but unchanged blood glucose levels. The disrupted lipid profiles were ameliorated by SAA, with significantly decreased levels of blood cholesterol, LDL-C and triglyceride. The protective effects of SAA against early AS were further confirmed by histopathological examination of aortic tissues. In addition, we observed that SAA decreased serum hs-CRP levels and suppressed the activation of NLRP3 inflammasome and NF-κB signaling in aortic tissues of ZDF rats. Collectively, our results demonstrate the potential of SAA to alleviate AS and T2DM in ZDF rats as a result of its anti-inflammatory effects.

Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been applied for many years, the toxicity of the mono-constituent of Salvia miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated the cardiotoxicity and developmental malformations of Tan-IIA by using zebrafish normal embryos and dechorionated embryos. After treatment with Tan-IIA in different concentrations for four-day periods, obvious pericardial edema, spinal curvature, and even missing tails were observed in zebrafish embryos. The LC50 values in the dechorionated embryo group at 72 h post-fertilization (hpf) and 96 hpf were 18.5 μM and 12.8 μM, respectively, and the teratogenicity was manifested at a concentration of about 1 µM. The main endpoints of teratogenicity were scoliosis, malformation of tail, and pericardium edema. Our findings displayed the potential cardiotoxicity and severe impact on the abnormal development of Tan-IIA in zebrafish embryo at high concentrations, which may help avoid the risk of its clinical application.

Mobile group consumption refers to consumption by a group of people, such as a couple, a family, colleagues and friends, based on mobile communications. It differs from consumption only involving individuals, because of the complex relations among group members. Existing data collection systems for mobile group consumption are centralized, which has the disadvantages of being a performance bottleneck, having single-point failure and increasing business and security risks. Moreover, these data collection systems are based on a synchronized clock, which is often unrealistic because of hardware constraints, privacy concerns or synchronization cost. In this paper, we propose the first asynchronous distributed approach to collecting data generated by mobile group consumption. We formally built a system model thereof based on asynchronous distributed communication. We then designed a simulation system for the model for which we propose a three-layer solution framework. After that, we describe how to detect the causality relation of two/three gathering events that happened in the system based on the collected data. Various definitions of causality relations based on asynchronous distributed communication are supported. Extensive simulation results show that the proposed approach is effective for data collection relating to mobile group consumption.