ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

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

Panax ginseng as a perennial herb of Araliaceae, exhibits pharmacological effects such as central nervous system stimulation, anti-tumor properties, and cardiovascular and cerebrovascular protection. The B3 gene family plays a crucial role in growth and development, antioxidant activity, stress resistance, and secondary metabolism regulation of plants and has been extensively studied in various plants. However, the identification and analysis of the B3 gene family in P. ginseng have not been reported. In this study, a total of 145 B3 genes(PgB3s) with complete open reading frames(ORF) were identified from P. ginseng and classified into five subfamilies based on domain types. Through correlation analysis with ginsenoside content, SNP/InDels analysis, and interaction analysis with key enzyme genes, 15 PgB3 transcripts were found to be significantly correlated with ginsenoside content and exhibited a close interaction network with key enzyme genes involved in ginsenoside biosynthesis, which indicated that these genes may participate in the regulation of ginsenoside biosynthesis. Additionally, this study found that PgB3 genes exhibited induced expression in response to methyl jasmonate(MeJA) stress, which aligned with the presence of abundant stress response elements in their promoters, confirming the important role of the B3 gene family in P. ginseng in stress resistance. The results of this study revealed the potential functions of PgB3 genes in ginsenoside biosynthesis and stress response, providing a significant theoretical basis for further research on the functions of PgB3 genes and their regulatory mechanisms.
Panax/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Ginsenosides/biosynthesis* ; Multigene Family ; Phylogeny