ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Quality control is a key link in the modernization process of traditional Chinese medicine(TCM). Studies have shown that the effects of active components in TCM depend on not only their chemical composition but also their suitable physical forms and states. The physical phase structures, such as micelles, vesicles, gels, and nanoparticles, can improve the solubility, delivery efficiency, and targeting precision of active components. These structures significantly enhance the pharmacological activity while reducing the toxicity and side effects, demonstrating functional activity surpassing that of active components and highlighting the key effects of "structures" on "functions" of active components. Taking the physical phase structure as a breakthrough point, this paper outlines the common types of TCM physical phase structures. Furthermore, this paper explores how to realize the quality upgrading of TCM through the precise regulation of physical phase structures based on the current applications and potential of TCM physical phase structures in processing to increase the efficacy and reduce the toxicity, compounding and decocting processes, drug delivery systems, and quality control, aiming to provide novel insights for the future quality control of TCM.
Quality Control ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional/standards* ; Humans ; Drug Delivery Systems

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

OBJECTIVE: To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL). METHODS: The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis. RESULTS: A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005). CONCLUSION The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Asparaginase/therapeutic use* ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Prognosis ; Retrospective Studies ; Survival Rate ; Polyethylene Glycols

OBJECTIVE: To investigate the action mechanism of formononetin (FN) in regulating T helper type 1 (Th1) cell differentiation and macrophage polarization through JAK/STAT signaling pathways in a mouse model of experimental autoimmune prostatitis (EAP). METHODS: Forty non-obese diabetic (NOD) male mice were randomly divided into four groups: normal control, EAP model control, low-dose FN (LFN, 50 mg/kg) and high-dose FN (HFN, 100 mg/kg). The EAP model was established in the latter three groups by subcutaneous injection of prostate antigens (PAgs) combined with complete Freund's adjuvant (CFA). After modeling, the mice in the LFN and HFN groups were treated intragastrically with FN at 50 and 100 mg/kg/d, respectively, and those in the normal and model controls groups with carboxymethylcellulose sodium (CMC-Na). At 42 days after treatment, all the animals were killed and relevant tissues collected for observation of the pathological changes in the prostate tissue by HE staining, detection of Th1 cell differentiation and macrophage polarization in the prostate by immunofluorescence double staining (labeling CD4 and interferon-γ ［IFN-γ］, inducible nitric oxide synthase ［iNOS］ and CD206), measurement of the ratio of Th1 cells/macrophages in the spleen by flow cytometry and the levels of IFN-γ and tumor necrosis factor-α (TNF-α) in the serum by ELISA, and determination of the expressions of phosphorylated (p)-Janus kinase (JAK)1, JAK1, p-JAK2, JAK2, p-signal transducer and activator of transcription (STAT1) in the prostate tissue by Western blot. RESULTS: Compared with the model controls, the mice treated with low- and high-dose FN exhibited more orderly arrangement of glandular epithelial cells, significantly reduced prostatic tissue inflammation scores (P<0.05), and decreased proportion of Th1 cells and expression of M1 macrophages (P<0.05), but increased expression of M2 macrophages in the prostate and spleen tissues (P<0.05). Besides, the levels of inflammatory cytokines IFN-γ (P<0.05) and TNF-α (P<0.05) in the serum of the mice in the LFN and HFN groups were remarkably reduced, and so were the ratios of p-JAK1/JAK1, p-JAK2/JAK2 and p-STAT1/STAT1 in the prostate tissues at the molecular level (P<0.05), indicating the therapeutic effect of FN on EAP by regulating JAK/STAT signaling pathways, promoting inflammation resolution, and restoring immune balance. CONCLUSION FN alleviates EAP by inhibiting JAK/STAT signaling pathways and regulating Th1 cell differentiation and macrophage polarization.
Animals ; Male ; Prostatitis/metabolism* ; Signal Transduction ; Mice ; Isoflavones/therapeutic use* ; Mice, Inbred NOD ; Autoimmune Diseases/metabolism* ; Macrophages ; Inflammation ; Th1 Cells ; Janus Kinases/metabolism* ; Cell Differentiation ; Disease Models, Animal ; STAT Transcription Factors/metabolism*

ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.

ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang （HQCFT） on rats with atherosclerosis （AS） by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D₃ injection， and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups： A blank group， a model group， a group receiving a low dose of HQCFT at 1.53 g·kg^-1 （HQCFT-L group）， a group receiving a high dose of HQCFT at 3.06 g·kg^-1 （HQCFT-H group）， and a group receiving atorvastatin calcium tablets at 1.8 mg·kg^-1 （Ato group）， with 10 rats in each group. Oral gavage administration started on the day after model establishment， once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin （HE） staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction （Real-time PCR） was used for detecting inflammatory factor levels in the aorta， high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents， targeted metabolomics for detecting short-chain fatty acid （SCFA） levels， and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group， the aortic tissue of rats in the model group showed significant AS lesions， including endothelial damage， inflammatory infiltration， and formation of fibrous plaques and calcified foci. Moreover， serum triacylglycerol （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） levels were significantly elevated （P<0.05）， while high-density lipoprotein cholesterol （HDL-C） levels were significantly reduced （P<0.05）. Significant increases were observed in whole blood viscosity， plasma viscosity， and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 （NLRP3）， Caspase-1， interleukin （IL）-β， IL-6， and tumor necrosis factor-α （TNF-α） in aortic tissue （P<0.05）. Additionally， gut microbiota composition， SCFA levels， and metabolomic profiles were significantly altered. Compared with those in the model group， serum TC， TG， and LDL-C levels， as well as the whole blood viscosity and plasma viscosity， were significantly reduced in all groups treated with HQCFT （P<0.05）. Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT， Caspase-1， IL-β， and IL-6 mRNA expression levels in the HQCFT-H group， and TNF-α mRNA expression levels in the HQCFT-L group （P<0.05）. HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid， valeric acid， and propionic acid. Non-targeted metabolomics identified 39 differential metabolites， which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition， promoting SCFA production， and regulating the levels of metabolites in intestinal contents.