ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

This study investigates the genetic diversity and evolutionary relationships of different Artemisia argyi germplasm resources to provide a basis for germplasm identification, variety selection, and resource protection. A total of 192 germplasm resources of A. argyi were studied, and EST-based simple sequence repeat(EST-SSR) primers were designed based on transcriptomic data of A. argyi. Polymerase chain reaction(PCR) amplification was performed on these resources, followed by fluorescence capillary electrophoresis to detect genetic diversity and construct DNA fingerprints. From 197 pairs of primers designed, 28 pairs with polymorphic and clear bands were selected. A total of 278 alleles were detected, with an average of 9.900 0 alleles per primer pair and an average effective number of alleles of 1.407 2. The Shannon's diversity index(I) for the A. argyi germplasm resources ranged from 0.148 1 to 0.418 0, with an average of 0.255 7. The polymorphism information content(PIC) ranged from 0.454 5 to 0.878 0, with an average of 0.766 9, showing high polymorphism. Cluster analysis divided the A. argyi germplasm resources into three major groups: Group Ⅰ contained 136 germplasm samples, Group Ⅱ contained 45, and Group Ⅲ contained 11. Principal component analysis also divided the resources into three groups, which was generally consistent with the clustering results. Mantel test results showed that the genetic variation in A. argyi populations was to some extent influenced by geographic distance, but the effect was minimal. Structure analysis showed that 190 germplasm materials had Q≥ 0.6, indicating that these germplasm materials had a relatively homogeneous genetic origin. Furthermore, 8 core primer pairs were selected from the 28 designed primers, which could distinguish various germplasm types. Using these 8 core primers, DNA fingerprints for the 192 A. argyi germplasm resources were successfully constructed. EST-SSR molecular markers can be used to study the genetic diversity and phylogenetic relationships of A. argyi, providing theoretical support for the identification and molecular-assisted breeding of A. argyi germplasm resources.
Artemisia/classification* ; Microsatellite Repeats ; Genetic Variation ; Expressed Sequence Tags ; DNA Fingerprinting ; Phylogeny ; Polymorphism, Genetic ; DNA, Plant/genetics* ; Genetic Markers

This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

In recent years, the study of single-cell transcriptome sequencing technology in the heterogeneity of astrocytes (astrocytes) after spinal cord injury (SCI) has provided new perspectives on post-traumatic nerve regeneration and repair. To provide a review on the research progress of single-cell sequencing technology in astrocytes after spinal cord injury (SCI), and to more comprehensively and deeply elaborate the application of single-cell sequencing technology in the field of astrocytes after SCI. Single-cell sequencing technology can analyse the transcriptomes of individual cells in a high-throughput manner, thus revealing fine differences in cell types and states. By using single-cell sequencing technology, the heterogeneity of astrocytes after SCI and their association with nerve regeneration and repair were revealed. In conclusion, the application of single-cell sequencing technology provides an important tool to reveal the heterogeneity of astrocytes after SCI, to further explore the mechanisms of astrocytes in SCI, and to develop intervention strategies targeting their regulatory mechanisms in order to improve the therapeutic efficacy of SCI. The discovery of changes in astrocyte transcriptome dynamics has improved researchers' understanding of spinal cord injury lesion progression and provided new insights into the treatment of spinal cord injury at different time points. To date, all of these findings need to be validated by more basic research and sufficient clinical trials. In the future, single-cell sequencing technology, through interdisciplinary collaboration with bioinformatics, computer science, tissue engineering, and clinical medicine, is expected to open a new window for the treatment of spinal cord injury.
Spinal Cord Injuries/metabolism* ; Astrocytes/cytology* ; Single-Cell Analysis/methods* ; Humans ; Animals ; Transcriptome ; Nerve Regeneration

PURPOSE: To analyze risk factors for severe trauma and establish a nomogram for early risk prediction, to improve the early identification of severe trauma. METHODS: This study was conducted on the patients treated in 81 trauma treatment institutions in Gansu province from 2020 to 2022. Patients were grouped by year, with 5364 patients from 2020 to 2021 as the training set and 1094 newly admitted patients in 2020 as the external validation set. Based on the injury severity score (ISS), patients in the training set were classified into 2 subgroups of the severe trauma group (n = 478, ISS scores ≥25) and the non-severe trauma group (n = 4886, ISS scores <25). Univariate and binary logistic regression analyses were employed to identify independent risk factors for severe trauma. Subsequently, a predictive model was developed using the R software environment. Furthermore, the model was subjected to internal and external validation via the Hosmer-Lemeshow test and receiver operating characteristic curve analysis. RESULTS: In total, 6458 trauma patients were included in this study. Initially, this study identified several independent risk factors for severe trauma, including multiple traumatic injuries (polytrauma), external hemorrhage, elevated shock index, elevated respiratory rate, decreased peripheral oxygen saturation, and decreased Glasgow coma scale score (all p < 0.05). For internal validation, the area under the receiver operating characteristic curve was 0.914, with the sensitivity and specificity of 88.4% and 87.6%, respectively; while for external validation, the area under the receiver operating characteristic curve was 0.936, with the sensitivity and specificity of 84.6% and 93.7%, respectively. In addition, a good model fitting was observed through the Hosmer-Lemeshow test and calibration curve analysis (p > 0.05). CONCLUSION This study establishes a nomogram for early risk prediction of severe trauma, which is suitable for primary healthcare institutions in underdeveloped western China. It facilitates early triage and quantitative assessment of trauma severity by clinicians prior to clinical interventions.
Humans ; Nomograms ; Male ; Female ; Wounds and Injuries/diagnosis* ; Risk Factors ; Middle Aged ; Adult ; Injury Severity Score ; Risk Assessment ; ROC Curve ; Aged ; Logistic Models ; China ; Glasgow Coma Scale

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*