Loss of ten-eleven translocation 2 induces cardiac hypertrophy and fibrosis through modulating ERK signaling pathway.

The ten-eleven translocation (Tet) family of dioxygenases convert 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC-mediated epigenetic modifications play essential roles in diverse biological processes and diseases. Here, we show that Tet proteins and 5hmC display dynamic features during postnatal cardiac development and that Tet2 is the predominant dioxygenase present in heart. Tet2 knockout results in abnormal cardiac function, progressive cardiac hypertrophy and fibrosis. Mechanistically, Tet2 deficiency leads to reduced hydroxymethylation in the cardiac genome and alters the cardiac transcriptome. Mechanistically, Tet2 loss leads to a decrease of Hspa1b expression, a regulator of the extracellular signal-regulated protein kinase (Erk) signaling pathway, which leads to over-activation of Erk signaling. Acute Hspa1b knock down (KD) increased the phosphorylation of Erk and induced hypertrophy of cardiomyocytes, which could be blocked by Erk signaling inhibitor. Consistently, ectopic expression of Hspa1b was able to rescue the deficits of cardiomyocytes induced by Tet2 depletion. Taken together, our study's results reveal the important roles of Tet2-mediated DNA hydroxymethylation in cardiac development and function.

Children's Pain Identification Based on Skin Potential Signal.

Pain management is a crucial concern in medicine, particularly in the case of children who may struggle to effectively communicate their pain. Despite the longstanding reliance on various assessment scales by medical professionals, these tools have shown limitations and subjectivity. In this paper, we present a pain assessment scheme based on skin potential signals, aiming to convert subjective pain into objective indicators for pain identification using machine learning methods. We have designed and implemented a portable non-invasive measurement device to measure skin potential signals and conducted experiments involving 623 subjects. From the experimental data, we selected 358 valid records, which were then divided into 218 silent samples and 262 pain samples. A total of 38 features were extracted from each sample, with seven features displaying superior performance in pain identification. Employing three classification algorithms, we found that the random forest algorithm achieved the highest accuracy, reaching 70.63%. While this identification rate shows promise for clinical applications, it is important to note that our results differ from state-of-the-art research, which achieved a recognition rate of 81.5%. This discrepancy arises from the fact that our pain stimuli were induced by clinical operations, making it challenging to precisely control the stimulus intensity when compared to electrical or thermal stimuli. Despite this limitation, our pain assessment scheme demonstrates significant potential in providing objective pain identification in clinical settings. Further research and refinement of the proposed approach may lead to even more accurate and reliable pain management techniques in the future.

Dynamic effects of Fto in regulating the proliferation and differentiation of adult neural stem cells of mice.

N 6-methyladenosine (m6A) modification of RNA is deposited by the methyltransferase complex consisting of Mettl3 and Mettl14 and erased by demethylase Fto and Alkbh5 and is involved in diverse biological processes. However, it remains largely unknown the specific function and mechanism of Fto in regulating adult neural stem cells (aNSCs). In the present study, utilizing a conditional knockout (cKO) mouse model, we show that the specific ablation of Fto in aNSCs transiently increases the proliferation of aNSCs and promotes neuronal differentiation both in vitro and in vivo, but in a long term, the specific ablation of Fto inhibits adult neurogenesis and neuronal development. Mechanistically, Fto deficiency results in a significant increase in m6A modification in Pdgfra and Socs5. The increased expression of Pdgfra and decreased expression of Socs5 synergistically promote the phosphorylation of Stat3. The modulation of Pdgfra and Socs5 can rescue the neurogenic deficits induced by Fto depletion. Our results together reveal an important function of Fto in regulating aNSCs through modulating Pdgfra/Socs5-Stat3 pathway.

Prediction of congenital heart disease for newborns: comparative analysis of Holt-Winters exponential smoothing and autoregressive integrated moving average models.

OBJECTIVE: To describe the temporal trend of the number of new congenital heart disease (CHD) cases among newborns in Jinhua from 2019 to 2020 and explored an appropriate model to fit and forecast the tendency of CHD. METHODS: Data on CHD from 2019 to 2020 was collected from a health information system. We counted the number of newborns with CHD weekly and separately used the additive Holt-Winters ES method and ARIMA model to fit and predict the number of CHD for newborns in Jinhua. By comparing the mean square error, rooted mean square error and mean absolute percentage error of each approach, we evaluated the effects of different approaches for predicting the number of CHD in newborns. RESULTS: A total of 1135 newborns, including 601 baby girls and 534 baby boys, were admitted for CHD from HIS in Jinhua during the 2-year study period. The prevalence of CHD among newborns in Jinhua in 2019 was 0.96%. Atrial septal defect was diagnosed the most frequently among all newborns with CHD. The number of CHD cases among newborns remained stable in 2019 and 2020. There were fewer cases in spring and summer, while cases peaked in November and December. The ARIMA(2,1,1) model relatively offered advantages over the additive Holt-winters ES method in predicting the number of newborns with CHD, while the accuracy of ARIMA(2,1,1) was not very ideal. CONCLUSIONS: The diagnosis of CHD is related to many risk factors, therefore, when using temporal models to fit and predict the data, we must consider such factors' influence and try to incorporate them into the models.

Trends in the disease burden of congenital heart disease in China over the past three decades.

OBJECTIVE: To investigate the disease burden of congenital heart disease (CHD) in China from 1990 to 2019. METHODS: Using the data from Global Burden of Disease (GBD) study 2019, the incidence, age-standardized incidence rates, the mortality, age-standardized mortality rates, disability-adjusted life year (DALY) and age-standardized DALY rates of CHD were calculated. Time trend analysis of disease burden-related indicators was analyzed by Joinpoint regression model. Age-period-cohort model was used to describe age, period, and birth cohort effects in CHD mortality population. The relationship between age-standardized incidence, mortality, DALY rates of congenital heart disease and human development index (HDI) were analyzed by Pearson correlation. RESULTS: From 1990 to 2019, the mean annual percentage change (AAPC) in age-standardized incidence rate, mortality rate and DALY rate of CHD in China were -0.1%(95% CI: -0.7%-0.4%)、-3.5%(95% CI: -3.7%--3.2%) and -3.5%(95% CI: -3.7%--3.2%), respectively. CHD usually occurred in the first year of life. The mean incidence rate at birth was 2497.9/100 000, and the mean incidence rate under 1 year of age was 2626.6/100 000. During the period of 1995-2000, the incidence rate in newborn and <1 year children showed an exponential upward trend, then it remained a steady downward trend. However, there was an exponential increase in <1 year children during 2010-2013 and 2014-2015, followed by an exponential decrease to the lowest value in the last three decades. The mortality of CHD tended to decrease with age, with mortality of 101.67/100 000 for children under 5 years of age and a decrease after 5 years of age. However, there was a transient increase in mortality in age group 55-<60. From 1995 to 2019, the relative risk of death of patients with CHD showed a downward trend. Compared with 1995-1999, the rate ratio of death decreased by 24% in 2015-2019. Such downward trend was also observed in the birth cohort after 1945. Compared with the 1945-1949 birth cohort, the rate ratio of death for patients with CHD decreased by 75% in the 2015-2019 birth cohort. When HDI<0.58 (before 1999), the age-standardized incidence of CHD was positively correlated with HDI ( r=0.74, P<0.05). When HDI≥0.58 (after 1999), the age-standardized incidence of CHD was negatively correlated with HDI ( r=-0.76, P<0.01). The age-standardized mortality and DALY rates were negatively correlated with HDI ( r=-0.95 and -0.93, both P<0.01). CONCLUSIONS: During 1990 to 1999, the incidence of CHD increases and is positively correlated with the social development. During 1999 to 2019, the incidence of CHD decreases and is negatively correlated with the social development. The disease burden of CHD decreases and is negatively correlated with the social development. Some progress has been made in the field of prevention and control of CHD, but the disease burden remains high among younger population in China.

Risk factors for re-dislocation after closed reduction in children with developmental dysplasia of the hip.

OBJECTIVE: To investigate the risk factors for re-dislocation after the closed reduction in children with developmental dysplasia of the hip (DDH). METHODS: The clinical data of 88 children aged ≤ 18 months with DDH (103 hips) who were treated with adductor muscle relaxation + closed reduction + plaster fixation at the Children's Hospital, Zhejiang University School of Medicine from January 2015 to December 2017, were retrospectively analyzed. According to the diagnostic criteria of hip dislocation, patients were divided into two groups: reduction group and re-dislocation group. The univariate and multivariate logistic regression analysis were applied to identify the risk factors for the re-dislocation of children. RESULTS: Eighty-six patients (99 hips) successively underwent the treatment. 69 hips were fixed at the first intention, 9 hips at the second intention, and a total of 78 hips with no re-dislocation occurred till the last follow-up with a rate of 78.8%. The univariate analysis showed that preoperative acetabular index (AI), International Hip Dysplasia Institute (IHDI) grade, intraoperative hip flexion angle, and intraoperative head-socket spacing were significantly related to the occurrence of re-dislocation after closed-reduction. The multivariate logistic regression analysis showed that preoperative AI > 40.5° ( OR=5.57, P<0.01), flexion angle < 80.5° ( OR=4.93, P<0.01) and head-socket distance > 6.95 mm ( OR=8.42, P<0.01) were risk factors for the re-dislocation. The area under the receiver operator characteristic curve was 0.91 when preoperative AI > 40.5°, flexion angle < 80.5°, head-socket distance > 6.95 mm, and IHDI grade were used to predict the occurrence of re-dislocation, and the sensitivity and specificity were 0.72 and 0.87, respectively. CONCLUSIONS: Preoperative AI > 40.5°, intraoperative hip flexion angle < 80.5°, and head-socket distance > 6.95 mm are risk factors for postoperative re-dislocation in children with DDH. These risk factors combining with the IHDI grade would be better to predict the occurrence of re-dislocation.

CoolBox: a flexible toolkit for visual analysis of genomics data.

BACKGROUND: Data visualization, especially the genome track plots, is crucial for genomics researchers to discover patterns in large-scale sequencing dataset. Although existing tools works well for producing a normal view of the input data, they are not convenient when users want to create customized data representations. Such gap between the visualization and data processing, prevents the users to uncover more hidden structure of the dataset. RESULTS: We developed CoolBox-an open-source toolkit for visual analysis of genomics data. This user-friendly toolkit is highly compatible with the Python ecosystem and customizable with a well-designed user interface. It can be used in various visualization situations like a Swiss army knife. For example, to produce high-quality genome track plots or fetch commonly used genomic data files with a Python script or command line, to explore genomic data interactively within Jupyter environment or web browser. Moreover, owing to the highly extensible Application Programming Interface design, users can customize their own tracks without difficulty, which greatly facilitate analytical, comparative genomic data visualization tasks. CONCLUSIONS: CoolBox allows users to produce high-quality visualization plots and explore their data in a flexible, programmable and user-friendly way.

Development and application of a recombination-based library versus library high- throughput yeast two-hybrid (RLL-Y2H) screening system.

Protein-protein interaction (PPI) network maintains proper function of all organisms. Simple high-throughput technologies are desperately needed to delineate the landscape of PPI networks. While recent state-of-the-art yeast two-hybrid (Y2H) systems improved screening efficiency, either individual colony isolation, library preparation arrays, gene barcoding or massive sequencing are still required. Here, we developed a recombination-based 'library vs library' Y2H system (RLL-Y2H), by which multi-library screening can be accomplished in a single pool without any individual treatment. This system is based on the phiC31 integrase-mediated integration between bait and prey plasmids. The integrated fragments were digested by MmeI and subjected to deep sequencing to decode the interaction matrix. We applied this system to decipher the trans-kingdom interactome between Mycobacterium tuberculosis and host cells and further identified Rv2427c interfering with the phagosome-lysosome fusion. This concept can also be applied to other systems to screen protein-RNA and protein-DNA interactions and delineate signaling landscape in cells.

[Artificial intelligence technology in cardiac auscultation screening for congenital heart disease: present and future].

The electronic stethoscope combined with artificial intelligence (AI) technology has realized the digital acquisition of heart sounds and intelligent identification of congenital heart disease, which provides objective basis for heart sound auscultation and improves the accuracy of congenital heart disease diagnosis. At the present stage, the AI based cardiac auscultation technique mainly focuses on the research of AI algorithms, and the researchers have designed and summarized a variety of effective algorithms based on the characteristics of cardiac audio data, among which the mel-frequency cepstral coefficients (MFCC) is the most effective one, and widely used in the cardiac auscultation. However, the current cardiac sound analysis techniques are based on specific data sets, and have not been validated in clinic, so the performance of algorithms need to be further verified. The lack of heart sound data, especially the high-quality, standardized, publicly available heart sound database with disease labeling, further restricts the development of heart sound diagnostic analysis and its application in screening. Therefore, expert consensus is necessary in establishing an authoritative heart sound database and standardizing the heart sound auscultation screening process for congenital heart disease. This paper provides an overview of the research and application status of auscultation algorithm and hardware equipment based on AI in auscultation screening of congenital heart disease, and puts forward the problems to be solved in clinical application of AI auscultation screening technology.

[Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)].

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

Low-Copy Number Polymorphism in DEFA1/DEFA3 Is Associated with Susceptibility to Hospital-Acquired Infections in Critically Ill Patients.

DEFA1/DEFA3, genes encoding human neutrophil peptides (HNP) 1-3, display wide-ranging copy number variations (CNVs) and is functionally associated with innate immunity and infections. To identify potential associations between DEFA1/DEFA3 CNV and hospital-acquired infections (HAIs), we enrolled 106 patients with HAIs and 109 controls in the intensive care unit (ICU) and examined their DEFA1/DEFA3 CNVs. DEFA1/DEFA3 copy number ranged from 2 to 16 per diploid genome in all 215 critically ill patients, with a median of 7 copies. In HAIs, DEFA1/DEFA3 CNV varied from 2 to 12 with a median of 6, which was significantly lower than that in controls (2 to 16 with a median of 8, p = 0.017). Patients with lower DEFA1/DEFA3 copy number (CNV < 7) were far more common in HAIs than in controls (52.8% in HAIs versus 35.8% in controls; p = 0.014; OR, 2.010; 95% CI, 1.164-3.472). The area under the receiver operating characteristic (AUROC) of DEFA1/DEFA3 CNV combined with clinical characteristics to predict the incidence of HAIs was 0.763 (95% CI 0.700-0.827), showing strong predictive ability. Therefore, lower DEFA1/DEFA3 copy number contributes to higher susceptibility to HAIs in critically ill patients, and DEFA1/DEFA3 CNV is a significant hereditary factor for predicting HAIs.

[Application of cameral-type three-dimensional scan in assessment of funnel chest].

OBJECTIVE: To evaluate the application of cameral-type three-dimensional (3D) scan in the assessment of funnel chest. METHODS: Eighty children with funnel chest were collected from the Children's Hospital, Zhejiang University School of Medicine during June 2016 and December 2017. All patients underwent routine CT scan. In the same selected mediastinal window, the lowest point of the depression to the front of the spine was the anteroposterior diameter (A1), and the maximum left to right diameter was B1 (which was perpendicular to A1). The ratio B1/A1 was calculated to get CT Haller index (CT-HI). In the same period, the chest wall scan was performed by EinScan-Pro 3D scanner, and the image was analyzed by GeoMedic image software. On the plane of the most concave point of the sternum, the distance from the lowest point of the skin to the back skin was the anteroposterior diameter (A2), the maximum plane diameter was measured on the same plane (B2), and the ratio B2/A2 was the 3D-Haller index (3D-HI). Pearson correlation analysis was used to analyze the consistency of the two measurements. Kappa test was used to analyze the consistency of surgical indication based on cutoff value of CT-HI and 3D-HI. RESULTS: All children were able to cooperate with CT and 3D chest wall surface scan. The mean value of CT-HI was 3.82±0.96, and that of 3D-HI was 1.82±0.23. Pearson correlation analysis showed that the correlation coefficient between CT-HI and 3D-HI was 0.823 (P<0.01). When CT-HI > 3.2 and 3D-HI > 1.7 were set as cutoff values for indication of operation, the sensitivity and specificity of 3D-HI were 90.48% and 100.0%, respectively. 3D-HI was well consistent with CT-HI in surgical indication (Kappa=0.801). CONCLUSIONS: s 3D scan can be used to assess the funnel chest in children, and 3D-HI>1.7 can be used as the cutoff value for surgical indication.

[Efficacy of percutaneous atrial septal defect closure guided by transesophageal echocardiography in children].

OBJECTIVE: To compare the efficacy of percutaneous atrial septal defect (ASD) closure guided by transesophageal echocardiography (TEE) or guided by fluoroscopy in pediatric patients. METHODS: Medical records of patients who underwent percutaneous ASD closure in the Children's Hospital, Zhejiang University School of Medicine from January 2017 to March 2018 were reviewed. There were 120 patients whose procedures were guided by TEE (TEE group), and 125 patients who had their procedures guided by fluoroscopy (fluoroscopy group). The performance of surgery, efficacy and postoperative complications were compared between two groups. RESULTS: Percutaneous ASD closure was successful in all patients. The operation time was shorter in the TEE group than that in fluoroscopy group[(20±14) min vs. (29±11) min, t=-7.939, P<0.05]. The size of the defect was larger in the TEE group than that of fluoroscopy group[(11±4) mm vs. (9±4) mm, t=2.512, P<0.05], but there was no significant difference in the sizes of occluder and occluder sheath between two groups (all P>0.05). No residual shunt, occluder shedding or displacement, severe arrhythmia or pericardial effusion were observed in either group. The incidence rates of fever, cough and diarrhea were not statistically different between two groups (all P>0.05). CONCLUSIONS: There was no significant difference in the outcome of percutaneous ASD closure guided by TEE or by fluoroscopy, but the procedure guided by TEE may reduce the operation time and can evaluate the size of ASD more accurately without involving radiation exposure, contrast agents use and large digital subtraction equipment.

Adaptive gene profiling of Mycobacterium tuberculosis during sub-lethal kanamycin exposure.

Resistance to anti-tuberculosis drugs is a formidable obstacle to effective tuberculosis (TB) treatment and prevention globally. New forms of multidrug, extensive drug and total drug resistance Mycobacterium tuberculosis (Mtb) causing a serious threat to human as well as animal's population. Mtb shows diverse adaptability under stress conditions especially antibiotic treatment, however underlying physiological mechanism remained elusive. In present study, we investigated Mtb's response and adaptation with reference to gene expression during sub-lethal kanamycin exposure. Mtb were cultured under sub-lethal drug and control conditions, where half were sub-cultured every 3-days to observe serial adaptation under same conditions and the remaining were subjected to RNA-seq. We identified 98 up-regulated and 198 down-regulated responsive genes compared to control through differential analysis, of which Ra1750 and Ra3160 were the most responsive genes. In adaptive analysis, we found Ra1750, Ra3160, Ra3161, Ra3893 and Ra2492 up-regulation at early stage and gradually showed low expression levels at the later stages of drug exposure. The adaptive expression of Ra1750, Ra3160 and Ra3161 were further confirmed by real time qPCR. These results suggested that these genes contributed in Mtb's physiological adaptation during sub-lethal kanamycin exposure. Our findings may aid to edify these potential targets for drug development against drug resistance tuberculosis.

ZCHSound: Open-Source ZJU Paediatric Heart Sound Database With Congenital Heart Disease.

Congenital heart disease (CHD) is a common birth defect in children. Intelligent auscultation algorithms have been proven to reduce the subjectivity of diagnoses and alleviate the workload of doctors. However, the development of this algorithm has been limited by the lack of reliable, standardized, and publicly available pediatric heart sound databases. Therefore, the objective of this research is to develop a large-scale, high-standard, high-quality, and accurately labeled pediatric CHD heart sound database. METHOD: From 2020 to 2022, we collaborated with experienced cardiac surgeons from three general children's hospitals to collect heart sound signals from 1259 participants using electronic stethoscopes. To ensure the accuracy of the labels, the labels for all data were confirmed by two cardiac experts. To establish the baseline of ZCHsound, we extracted 84 features and used machine learning models to evaluate the performance of the classification task. RESULTS: The ZCHSound database was divided into two datasets: one is a high-quality, filtered clean heart sound dataset, and the other is a low-quality, noisy heart sound dataset. In the evaluation of the high-quality dataset, our random forest ensemble model achieved an F1 score of 90.3% in the classification task of normal and pathological heart sounds. CONCLUSION: This study has successfully established a large-scale, high-quality, rigorously standardized pediatric CHD sound database with precise disease diagnosis. This database not only provides important learning resources for clinical doctors in auscultation knowledge but also offers valuable data support for algorithm engineers in developing intelligent auscultation algorithms.

Spatial multi-omics at subcellular resolution via high-throughput in situ pairwise sequencing.

Technology for spatial multi-omics aids the discovery of new insights into cellular functions and disease mechanisms. Here we report the development and applicability of multi-omics in situ pairwise sequencing (MiP-seq), a method for the simultaneous detection of DNAs, RNAs, proteins and biomolecules at subcellular resolution. Compared with other in situ sequencing methods, MiP-seq enhances decoding capacity and reduces sequencing and imaging costs while maintaining the efficacy of detection of gene mutations, allele-specific expression and RNA modifications. MiP-seq can be integrated with in vivo calcium imaging and Raman imaging, which enabled us to generate a spatial multi-omics atlas of mouse brain tissues and to correlate gene expression with neuronal activity and cellular biochemical fingerprints. We also report a sequential dilution strategy for resolving optically crowded signals during in situ sequencing. High-throughput in situ pairwise sequencing may facilitate the multidimensional analysis of molecular and functional maps of tissues.

A deep learning-based method for pediatric congenital heart disease detection with seven standard views in echocardiography.

Background: With the aggregation of clinical data and the evolution of computational resources, artificial intelligence-based methods have become possible to facilitate clinical diagnosis. For congenital heart disease (CHD) detection, recent deep learning-based methods tend to achieve classification with few views or even a single view. Due to the complexity of CHD, the input images for the deep learning model should cover as many anatomical structures of the heart as possible to enhance the accuracy and robustness of the algorithm. In this paper, we first propose a deep learning method based on seven views for CHD classification and then validate it with clinical data, the results of which show the competitiveness of our approach. Methods: A total of 1411 children admitted to the Children's Hospital of Zhejiang University School of Medicine were selected, and their echocardiographic videos were obtained. Then, seven standard views were selected from each video, which were used as the input to the deep learning model to obtain the final result after training, validation and testing. Results: In the test set, when a reasonable type of image was input, the area under the curve (AUC) value could reach 0.91, and the accuracy could reach 92.3%. During the experiment, shear transformation was used as interference to test the infection resistance of our method. As long as appropriate data were input, the above experimental results would not fluctuate obviously even if artificial interference was applied. Conclusions: These results indicate that the deep learning model based on the seven standard echocardiographic views can effectively detect CHD in children, and this approach has considerable value in practical application.

The influence of psychological factors on coronary heart disease: A review of the evidence and implications for psychological interventions.

This article reviews the evidence on the influence of psychological factors on coronary heart disease (CHD) and discusses the implications of these findings for psychological interventions. The review focuses on the role of work stress, depression, anxiety, and social support in the impact of CHD, as well as the effects of psychological interventions on CHD. The article concludes with recommendations for future research and clinical practice.

Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction has been extensively used to treat ulcerative colitis (UC) in recent years. Pulsatilla chinensis saponin (PRS), the active ingredient of its monarch medicine Pulsatilla chinensis (Bunge) Regel, plays a crucial role in the treatment of UC, but its specific mechanism of action has not been fully elucidated. AIM OF THE STUDY: This study aims to investigate the protective effect and possible mechanism of PRS on DSS-induced ulcerative colitis in rats. MATERIALS AND METHODS: In this study, the DSS-induced colitis model was used to explore the metabolism and absorption of PRS under UC, detect the content of short-chain fatty acids (SCFAs) in colon tissue, the expression of receptor G Protein-Coupled Receptor 43 (GPR43) protein and inflammasome NLRP3, and observe the expression level of IL-1ß, IL-6 and TNF-α in colon tissue. The protective effect of the PRS was also observed. RESULTS: It was found that in the UC group, the absorption rate and extent of drugs increased, and the elimination was accelerated. Compared with the control group, PRS increased the content of short-chain fatty acids (SCFAs) in colon tissue, promoted the expression of SCFAs receptor GPR43 protein, inhibited the activation of the NLRP3 inflammasome, and decreased the content of IL-1ß, IL-6 and TNF-α. PRS protects the colon in DSS-induced inflammatory bowel disease by increasing the content of SCFAs, promoting the expression of GPR43 protein, inhibiting the activation of the NLRP3 inflammasome, and reversing the increase in IL-1ß, IL-6 and TNF-α levels. CONCLUSIONS: PRS can increase the content of colonic SCFAs, activate the GPR43-NLRP3 signaling pathway, and reduce the levels of pro-inflammatory cytokines, thereby improving the symptoms of DSS-induced colitis.

Trends in the prevalence of elevated cardiovascular risk and the control of its risk factors Among US adults, 2001-2020.

Background: An accurate assessment of current trends in cardiovascular risks could inform public health policy. This study aims to determine 20-year trends in the prevalence of elevated cardiovascular risk and its risk factors' control among US adults. Methods: In this serial cross-sectional analysis of 23,594 adults, aged 40-79 years, without clinical atherosclerotic cardiovascular disease (ASCVD) in the National Health and Nutrition Examination Survey from 2001 to 2020, we calculated the prevalence of elevated cardiovascular risk (10-year ASCVD risk ≥ 7.5%) for all participants and subgroups with their risk factors controlled for diabetes, hypertension, or dyslipidemia. Results: The age- and sex-adjusted prevalence of elevated cardiovascular risk slightly decreased from 41.5% (95% CI, 39.7-43.3%) in 2001-2004 to 38.6% (95% CI, 36.1-41.1%) in 2017-2020 (P for trend = 0.169) while the respective sex-adjusted prevalence significantly increased from 34.4% (95% CI, 32.8-36.0%) to 39.5% (95% CI, 37.0-42.0%; P for trend <0.001). Sex and race continued to show disparities in cardiovascular risk. Furthermore, a worsening disparity in age- and sex-adjusted prevalence of elevated cardiovascular risk between young and old and a narrowing gap among different education and poverty index levels (all P trend for interaction <0.05). Differential decomposition analysis found that demographic changes (primarily population aging) led to an 8.8% increase in the prevalence of elevated cardiovascular risk from 2001 to 2004 to 2017-2020, while risk factor control led to a 3.8% decrease. The rate of individuals receiving treatment for diabetes, hypertension, or dyslipidemia increased significantly between 2001 and 2020 (all P for trend <0.05). The rate of participants with hypertension who achieved blood pressure under 130/80 mmHg and those with dyslipidemia who achieved a non-high-density lipoprotein cholesterol level under 130 mg/dl increased significantly (all P for trend <0.001). Conclusions: There is a slight reduction in the prevalence of age- and sex-adjusted elevated cardiovascular risk among US adults without clinical ASCVD between 2001 and 2020, while the sex-adjusted prevalence significantly increased. The decrease in elevated cardiovascular risk prevalence was mainly attributed to risk factor control, while demographic changes contributed to an increase.