Coronary heart disease is a cardiovascular disease that affects coronary arteries. It presents high incidence and high mortality worldwide, bringing a serious threat to human health and quality of life. Salviae Miltiorrhizae Radix et Rhizoma derived from Salvia miltiorrhiza is widely used in the treatment of cardiovascular diseases, such as coronary heart disease. Salvianolic acid B is an active component in Salviae Miltiorrhizae Radix et Rhizoma extracts, and studies have shown that it has anti-inflammatory, antioxidant, apoptosis-and autophagy-regulating, anti-fibrosis, and metabolism-modulating effects. This article reviews the research progress regarding the therapeutic effect of salvianolic acid B on coronary heart disease in the recent decade. It elaborates on the role and mechanism of salvianolic acid B in treating coronary heart disease from multiple perspectives, such as the inhibition of thrombosis, improvement of blood circulation, reduction of myocardial cell injury, and inhibition of cardiac remodeling. This article provides a theoretical basis for the application of Chinese medicinal materials and TCM prescriptions containing salvianolic acid B in the treatment of coronary heart disease.
Humans ; Benzofurans/administration & dosage* ; Coronary Disease/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Salvia miltiorrhiza/chemistry* ; Animals ; Depsides

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

Objective: To create a prediction model for stroke risk among middle-aged and elderly populations, so as to provide a basis for early identification of high-risk population for stroke. Methods: From October to December 2023, residents aged ≥45 years in Chongchuan District, Nantong City, Jiangsu Province were selected using a multi-stage stratified random sampling method. The demographic information, life behavior, and chronic disease data were collected through a questionnaire survey. The standardized prevalence of stroke was calculated using data from the seventh National Population Census. The subjects were randomly divided into the training set and the internal validation set according to the ratio of 8∶2. The basic demographic information, life behavior, and chronic diseases of residents aged ≥45 years in Rugao City were collected from July to August 2023 as the external validation set. Predictive factors were selected using multivariable logistic regression model, and a nomogram for stroke among residents aged ≥45 years was established. The prediction effect was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and Hosmer-Lemeshow goodness of fit test. Results: A total of 6 290 residents aged ≥45 years were included, including 2 975 males (47.30%) and 3 315 females (52.70%). The average age was (61.90±10.20) years. The prevalence of stroke was 3.80%, and the standardized prevalence was 3.36%. The multivariable logistic regression showed that age, smoking, hypertension, and hyperlipidemia were predictors of stroke risk among residents aged ≥45 years, and the prediction model was ln[p/(1-p)]=-4.619+0.046×age+0.383×smoking+0.887×hypertension+0.678×hyperlipidemia. The AUC values of the training set, internal validation set, and external validation set were 0.748, 0.755, and 0.738, respectively. The consistency indexes were 0.748, 0.755, and 0.738, respectively. The Hosmer-Lemeshow goodness of fit test showed a good fitting effect (P>0.05). Conclusion The prediction model based on age, smoking, hypertension, and hyperlipidemia has good discrimination and calibration, and can be used to predict the risk of stroke among middle-aged and elderly populations aged ≥45 years.

OBJECTIVE: To observe the effects of electroacupuncture (EA) with different frequencies on spermatogenic function, testicular morphology and oxidative stress in oligoasthenospermia (OAT) rats, and to explore the mechanism and the optimal parameters of EA for OAT. METHODS: Sixty SPF-grade male SD rats were randomly divided into a solvent control group, a model group, a 2 Hz EA group, a 100 Hz EA group and a 2 Hz/100 Hz EA group, with 12 rats in each group. Except for the solvent control group, the other 4 groups were administered ornidazole suspension (800 mg·kg^-1·d^-1) by gavage for 28 d to establish the OAT model. Starting from the 1st of modeling, EA was applied at "Guanyuan" (CV4), "Qihai" (CV6) and bilateral "Sanyinjiao" (SP6) and "Zusanli" (ST36) in the 3 EA groups, continuous wave of 2 Hz, continuous wave of 100 Hz, and disperse-dense wave of 2 Hz/100 Hz were used in the 2 Hz EA group, the 100 Hz EA group, and the 2 Hz/100 Hz EA group, respectively, with current intensity of 1-3 mA, 30 min a time, once every other day, for 28 consecutive days. After intervention, the testicular index was calculated, epididymal sperm quality was assessed, and the fertility ability was observed; morphology of testicular tissue was observed by HE staining, and the Johnson score was calculated; the positive expression of reactive oxygen species (ROS) in testicular tissue was detected by immunofluorescence; the activity of superoxide dismutase (SOD) and catalase (CAT), as well as the level of malondialdehyde (MDA) in testicular tissue were measured by ELISA; the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in testicular tissue was detected by Western blot. RESULTS: Compared with the solvent control group, in the model group, the testicular index, sperm concentration, sperm motility and the number of offspring were decreased (P<0.01), the seminiferous tubules atrophied and the Johnson score decreased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were decreased (P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were increased (P<0.01). Compared with the model group, in the 2 Hz EA group, the 100 Hz EA group and the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility and the number of offspring were increased (P<0.05, P<0.01), the pathological morphology of testicular tissue improved and the Johnson scores increased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were increased (P<0.05, P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were decreased (P<0.05, P<0.01). Compared with the 2 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility, as well as the CAT activity and HO-1 protein expression in testicular tissue were increased (P<0.01, P<0.05); the positive expression of ROS was decreased (P<0.01). Compared with the 100 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index was increased (P<0.01), the positive expression of ROS in testicular tissue was decreased (P<0.01). CONCLUSION EA with 2 Hz continuous wave, 100 Hz continuous wave, and 2 Hz/100 Hz disperse-dense wave can all improve the spermatogenic arrest and reduce the level of oxidative stress in testicular tissue in OAT rats, the mechanism may be related to up-regulating the protein expression of Nrf2 and HO-1 and improving oxidative stress. EA with disperse-dense wave of 2 Hz/100 Hz shows the optimal effect.
Male ; Animals ; Electroacupuncture ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; Oligospermia/genetics* ; Humans ; Testis/metabolism* ; Superoxide Dismutase/metabolism* ; Asthenozoospermia/genetics* ; Acupuncture Points ; Malondialdehyde/metabolism*

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

OBJECTIVES: To explore the risk factors of feeding intolerance (FI) in critically ill children receiving enteral nutrition (EN) and to construct a prediction nomogram model for FI. METHODS: A retrospective study was conducted to collect data from critically ill children admitted to the Pediatric Intensive Care Unit of Xiangya Hospital, Central South University, between January 2015 and October 2020. The children were randomly divided into a training set (346 cases) and a validation set (147 cases). The training set was further divided into a tolerance group (216 cases) and an intolerance group (130 cases). Multivariate logistic regression analysis was used to screen for risk factors for FI in critically ill children receiving EN. A nomogram was constructed using R language, which was then validated on the validation set. The model's discrimination, calibration, and clinical net benefit were evaluated using receiver operating characteristic curves, calibration curves, and decision curves. RESULTS: Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition were identified as independent risk factors for FI in critically ill children receiving EN (P<0.05). Based on these factors, a nomogram prediction model for FI in critically ill children receiving EN was developed. The area under the receiver operating characteristic curve for the training set and validation set was 0.934 (95%CI: 0.906-0.963) and 0.852 (95%CI: 0.787-0.917), respectively, indicating good discrimination of the model. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit (χ 2=12.559, P=0.128). Calibration curve and decision curve analyses suggested that the model has high predictive efficacy and clinical application value. CONCLUSIONS Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition are independent risk factors for FI in critically ill children receiving EN. The nomogram model developed based on these factors exhibits high predictive efficacy and clinical application value.
Humans ; Critical Illness ; Enteral Nutrition/adverse effects* ; Male ; Risk Factors ; Female ; Child, Preschool ; Infant ; Nomograms ; Retrospective Studies ; Child ; Logistic Models

OBJECTIVES: To explore the manifestations of sensory hypersensitivity in children with autism spectrum disorder (ASD) and individuals with subclinical autistic traits. METHODS: From September 2021 to April 2023, interviews were conducted on 18 college students with high levels of autistic traits and sensory hypersensitivity selected using the Adolescent/Adult Sensory Profile and the Autism Spectrum Quotient (as subclinical group). Interviews were also conducted on the parents of 11 children with ASD aged 6-13 years selected using the intensity sampling method (as clinical group). Qualitative content analysis and thematic analysis were performed on the interview texts to investigate the scenarios and impact of sensory hypersensitivity and coping strategies in the two groups. RESULTS: The Autism Spectrum Quotient score was significantly positively correlated with sensory hypersensitivity (r=0.504, P<0.001; n=225). Sensory modalities that triggered sensitive reactions were similar in the subclinical and clinical groups, with auditory hypersensitivity being the most prominent. Sensory hypersensitivity had significant negative impact on emotional wellbeing, cognitive ability, physical health, interpersonal relationships, and general adaptive functioning. These dimensions were interconnected, culminating in a holistic experience. Avoidance was the most commonly used coping mechanism for both groups (16 subclinical participants mentioned it 44 times; 8 clinical participants mentioned it 40 times). The clinical group required more support and help from their caregivers (18 times), while the subclinical group used more proactive coping strategies (e.g., facing sensitive scenarios, distracting attention) to alleviate the negative impact (51 times). CONCLUSIONS Sensory hypersensitivity is a common manifestation across the broad ASD phenotype, posing negative effects on multiple aspects of their lives. There is an urgent need for social tolerance and acceptance as well as the development of effective intervention measures.
Humans ; Child ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Adolescent ; Adaptation, Psychological ; Autistic Disorder/psychology* ; Sensation Disorders/etiology* ; Qualitative Research

A male full-term neonate was admitted at 30 minutes of life with pallor and 10 minutes of respiratory distress. Physical examination revealed pallor, increased intercanthal distance, low-set ears, a palpable cystic mass in the neck, hepatomegaly, a pedunculated, globular appendage attached to the right thumb, and an ectopic toenail on the right second toe. Laboratory testing showed severe anemia with hemoglobin of 44 g/L. Bone marrow examination demonstrated hypoplasia. Whole-exome sequencing identified a heterozygous pathogenic variant in the RPS19 gene, c.175T>C (p.Ser59Pro), establishing the diagnosis of Diamond-Blackfan anemia. On follow-up to 2 years and 2 months of age, both hemoglobin and reticulocyte counts remained within normal ranges. This case illustrates early-onset severe anemia in a neonate with genetically confirmed Diamond-Blackfan anemia and expands the phenotypic spectrum, informing clinical recognition and management.
Humans ; Anemia, Diamond-Blackfan/diagnosis* ; Male ; Infant, Newborn ; Ribosomal Proteins/genetics*