BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Based on whole genome data, the identification and expression pattern analysis of the Atropa belladonna WRKY transcription factor family were conducted to provide a theoretical foundation for studying the biological functions and mechanisms of these transcription factors. In this study, bioinformatics methods were employed to identify members of the A. belladonna WRKY gene family and to predict their physicochemical properties, conserved motifs, promoter cis-acting elements, and chromosomal localization. Additionally, the expression patterns of the A. belladonna WRKY gene family under the regulation of environmental factors such as light quality and temperature were analyzed. The results revealed a total of 28 AbWRKY transcription factors, randomly distributed across 16 chromosomes, encoding 324-707 amino acids. Most AbWRKY proteins were acidic, unstable, and hydrophilic. Based on multiple sequence alignment and phylogenetic analysis, the WRKY gene family members were classified into two subfamilies. Conserved motif and domain analysis indicated that WRKY transcription factors in the same subfamily possessed conserved structural features. Promoter analysis predicted that the A. belladonna WRKY family contained light-responsive elements, hormone-responsive elements, and stress-responsive elements. Collinearity analysis showed that AbWRKY24 plays a crucial role in the expansion of the AbWRKY gene family. Then qRT-PCR results indicated that AbWRKY6, AbWRKY8, AbWRKY14, and AbWRKY24 responded to red light stress, while AbWRKY8, AbWRKY14, and AbWRKY24 responded to yellow light/low-temperature combined stress. AbWRKY6 and AbWRKY8 were significantly expressed in leaves and stems, AbWRKY27 and AbWRKY28 were significantly expressed in fibrous roots, and AbWRKY25 was significantly expressed in flowers. This study is the first to identify and analyze the WRKY gene family in A. belladonna and to examine its expression patterns under light and temperature regulation, laying a foundation for in-depth analysis and functional validation of the molecular mechanisms of A. belladonna WRKY transcription factors in responding to light quality and temperature environmental factors.
Transcription Factors/chemistry* ; Plant Proteins/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Light ; Temperature ; Atropa belladonna/metabolism* ; Multigene Family/genetics* ; Promoter Regions, Genetic/genetics* ; Sequence Alignment ; Amino Acid Sequence ; Genome, Plant/genetics*

This study aimed to investigate the mechanism by which Shegan Mahuang Decoction(SGMH) and its bitter Chinese herbs(BCHs) regulated the lung-gut axis through the bitter taste receptor 14(TAS2R14)/secretory immunoglobulin A(SIgA)/thymic stromal lymphopoietin(TSLP) to intervene in the epithelial cell barrier of cold asthma rats. Fifty SD rats were randomly divided into the following five groups: normal group, model group, dexamethasone group, SGMH group, and BCHs group. A 10% ovalbumin(OVA) solution was used to sensitize the rats via subcutaneous injection on both sides of the abdomen and groin, combined with 2% OVA atomization and cold(2-4 ℃) stimulation to induce a cold asthma model in rats. The SGMH, BCHs, and dexamethasone groups were given corresponding treatments by gavage and nebulization, while the normal and model groups received normal saline by gavage and nebulization. After the final stimulation, pathological changes in the lung and intestine tissues were observed using hematoxylin-eosin(HE) and periodic acid-Schiff(PAS) staining. Lung function was assessed by measuring the ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC), the ratio of the average flow rate at 25%-75% of forced vital capacity to foned vital capacity(FEV25%-75%/FVC), the peak expiratory flow(PEF), and pulmonary resistance(RL). The levels of IL-4, IL-5, IL-13, and TNF-α in serum, and sIgA in serum, intestinal, and bronchial mucosa were detected by enzyme-linked immunosorbent assay(ELISA). The expression of TAS2R14 protein in lung tissue was detected by Western blot(WB). The content of short-chain fatty acids(SCFAs) in rat feces was determined by gas chromatography-mass spectrometry(GC-MS). The effect of TAS2R14/TSLP on lipopolysaccharide(LPS)-induced inflammation in epithelial cells in the BCHs group was observed, and the expression of TAS2R14 and TSLP in cells was detected by WB. Compared with the normal group, the model group showed reduced water intake, diet, and body weight, increased infiltration of inflammatory cells in the lung and intestinal tissues, goblet cell hyperplasia, significantly decreased FEV1/FVC, FEV25%-75%/FVC, and PEF, and significantly increased RL. Moreover, serum levels of IL-4, IL-5, IL-13, and TNF-α were elevated, and sIgA levels in serum, intestine, and bronchial mucosa were significantly decreased. TAS2R14 expression in lung tissues was inhibited, and the content of acetic acid, propionic acid, and butyric acid in feces was significantly reduced. In the LPS group, TSLP expression increased, and TAS2R14 expression decreased. Compared with the model group, the general condition of rats in the SGMH and BCHs groups improved, with reduced infiltration of inflammatory cells and goblet cell hyperplasia in the lung and intestinal tissues. FEV1/FVC, FEV25%-75%/FVC, and PEF significantly increased, and RL significantly decreased. Serum levels of IL-4, IL-5, IL-13, and TNF-α decreased, while sIgA levels in serum, intestine, and bronchial mucosa significantly increased, and TAS2R14 expression was activated in lung and intestinal tissues. The content of acetic acid, propionic acid, and butyric acid in feces significantly increased. Compared with the model group, the BCHs group and the agonist group showed inhibited TSLP expression and increased TAS2R14 expression. The results showed that both SGMH and BCHs could reduce lung and intestinal inflammatory reactions, improve lung function, and regulate the content of intestinal SCFAs in asthmatic rats. There was no significant difference in TAS2R14 protein expression between the SGMH and BCHs groups, indicating that the clinical efficacy of BCHs may be related to the activation of the bitter receptor TAS2R14 and the regulation of immune inflammatory mediators in lung and intestinal epithelial cells.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Lung/metabolism* ; Asthma/metabolism* ; Cytokines/immunology* ; Male ; Receptors, G-Protein-Coupled/immunology* ; Epithelial Cells/metabolism* ; Thymic Stromal Lymphopoietin ; Immunoglobulin A, Secretory/genetics* ; Humans ; Cold Temperature

This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including β-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.
Humans ; Nasal Lavage Fluid ; Rhinitis, Allergic/drug therapy* ; Metabolomics/methods* ; Metabolome

Objective: To analyze the current nutritional composition of commonly consumed prepackaged foods among children in Chengdu and to provide a scientific basis for health education among children and adolescents. Methods: Based on the 3 day and 24 hour dietary data of children aged 6-12 in Chengdu of the Southwest China Childhood Nutrition and Growth Cohort from 2021 to 2022, the nutritional information of prepackaged foods was collected by combining offline and online methods. All foods were classified step by step, and the nutrient content of each 100 g or 100 mL food was counted and graded. Results: A total of 1 902 children s prepackaged foods in 23 sub categories of 10 major categories were investigated. Nuts and seeds, snack foods, instant foods and other dairy products had higher total energy(2 476, 2 027, 1 728, 1 816 kJ/100 g), with the nutrient reference value percentage(NRV%) exceeding 20%. Fish, poultry, meat, eggs and their products had the highest protein content(22.8 g/ 100 g ) with an NRV% of 38%, nuts and seeds had the highest fat content(47.5 g/100 g) with an NRV% of 79%, confectionery and jelly had the highest carbohydrate content(82.1 g/100 g) with an NRV% of 27%, and seasoning flour products had the highest sodium content with an NRV% up to 118%. Seasoning flour products and instant foods were mostly high sodium, high fat and high carbohydrate food. Baked and puffed foods were almost high fat and high carbohydrate. Fish, poultry, meat, eggs, beans and their products were rich in protein but mostly high in sodium. Beverages and cold drinks were low in other nutrients except carbohydrate. Conclusion The nutrient content of various prepackaged foods commonly consumed by children in Chengdu are quite different. Most of the foods consumed by children are high sodium, high fat and/or high carbohydrate. Nutrition education should be strengthened to help children choose healthy foods.

OBJECTIVE: To evaluate the feasibility and safety of Liuzijue exercise (LE) for the clinical effect in patients after cardiac surgery. METHODS: Totally 120 patients who underwent cardiac surgery and were admitted to the Cardiothoracic Intensive Care Unit of Nanjing Drum Tower Hospital between July and Oclober, 2022 were allocated to the LE group, the conventional respiratory training (CRT) group, and the control group by a random number table at a ratio of 1:1:1; 40 patients in each group. All patients received routine treatment and cardiac rehabilitation. LE group and CRT group respectively performed LE and CRT once a day for 30 min for 7 days. Control group did not receive specialized respiratory training. The forced vital capacity, forced expiratory volume in 1 s, peak inspiratory flow rate, peak expiratory flow rate, maximum inspiratory pressure, maximum expiratory pressure, modified Barthel index (MBI), and Hamilton Rating Scale for Anxiety (HAM-A) were evaluated before, after 3 and 7 days of intervention. In addition, the postoperative length of hospital stay (LOS) and the adverse events that occurred during the intervention period were compared. RESULTS: A total of 107 patients completed the study, 120 patients were included in the analysis. After 3 days of intervention, the pulmonary function, respiratory muscle strength, MBI and HAM-A of all 3 groups improved compared with that before the intervention (P<0.05 or P<0.01). Compared with the control group, pulmonary function and respiratory muscle strength were significantly improved in the CRT and LE groups (P<0.05 or P<0.01). MBI and HAM-A were significantly improved in the LE group compared with the control and CRT groups (P<0.05 or P<0.01). On the 7th day after intervention, the difference was still statistically significant (P<0.01), and was significantly different from that on the 3rd day (P<0.05 or P<0.01). In addition, on the 7th day of intervention, the pulmonary function and respiratory muscle strength in the LE group were significantly improved compared with those in the CRT group (P<0.01). MBI and HAM-A were significantly improved in the CRT group compared with the control group (P<0.01). There were no significant differences in postoperative LOS among the 3 groups (P>0.05). No training-related adverse events occurred during the intervention period. CONCLUSIONS LE is safe and feasible for improving pulmonary function, respiratory muscle strength, the ability to complete activities of daily living and for relieving anxiety of patients after cardiac surgery (Registration No. ChiCTR2200062964).
Humans ; Activities of Daily Living ; Breathing Exercises ; Cardiac Surgical Procedures/adverse effects* ; Respiratory Muscles ; Muscle Strength/physiology*

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*