ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

Objective To construct a mindfulness-based self-care intervention program for patients with chronic heart failure(CHF)and their caregivers based on binary disease management theory and explore its small-scale application effect.Methods A prospective study was conducted on 100 pairs of CHF patients admitted to our hospital and their caregivers from January 2024 to October 2024.After excluding those with invalid survey data,92 pairs were finally included and randomly divided into an observation group and a control group,each consisting of 46 pairs.The control group received routine nursing care,while the observation group received the mindfulness-based self-care program based on binary disease management theory in addition to routine nursing care.The Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),Self Compassion Scale(SCS),and Mindfulness Attention Awareness Scale(MAAS)were used to compare the anxiety,depression,self-care,and mindfulness levels of patients and caregivers at three time points:pre-intervention(T1),right post-intervention(T2),and one month post-intervention(T3).The Caregiver Positive Perception Scale(PAC)was used to evaluate the caregiver's positive perception at each time point.Results The HAMA and HAMD scores of patients and caregivers in the observation group were lower than those in the control group at T2 and T3,while the SCS scores were signifi-cantly higher(all P<0.05).Repeated-measures analysis of variance showed significant differences in HAMA,The mindfulness-based self-care intervention program based on binary disease management theory effectively reduces negative emotions in patients and caregivers,and improves mindfulness and self-care,showing clinical application potential.

Objective To elucidate the molecular mechanisms underlying the effects of Kanggan Mixture(KGM)on key targets in rats with acute lung injury,network pharmacology and in vivo micro-CT experiments were employed.Methods Network pharmacology was utilized to forecast the target genes and principal pathways involved in the intervention of KGM in acute lung injury(ALI).Lipopolysaccharide(LPS)-induced ALI rat models were utilized,and micro-computed tomography(micro-CT)was employed to evaluate the extent of lung injury in vivo.Experiments were conducted to verify the intervention mechanism of KGM on ALI rats.Results The findings revealed that 190 chemical constituents were identified from KGM,and 579 potential targets and 204 pathways associated with KGM's impact on ALI were predicted.The principal components of KGM,such as quercetin,luteolin,kaempferol,betulin,and lupenone,exhibit anti-viral,anti-inflammatory,and immunomodulatory properties by targeting TP53,AKT1,SRC,EP300,and STAT3,and modulating the FoxO signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,demonstrating an influence on acute lung injury.Micro-CT results suggest that KGM can improve lung texture enhancement and lung injury in ALI rats,with an increase in end-expiratory lung volume(inspiratory phase-expiratory phase).The HE and W/D ratio results indicate that KGM can improve lung tissue injury and reduce the lung tissue wet/dry weight ratio(P<0.01).Blood cell analysis results show that the anti-inflammatory agent can decrease the WBC(white blood cell count)and N%(neutrophil percentage)in ALI rats'blood(P<0.01),and increase lymphocytes(P<0.05).Real-time quantitative PCR,WES,and immunohistochemistry results suggest that KGM can decrease the mRNA expression,protein distribution,and protein expression levels of TP53,AKT1,SRC,EP300,and STAT3 in lung tissue of ALI rats(P<0.05).Conclusion KGM has a certain intervention effect on acute lung injury,mainly achieved through the core targets STAT3,EP300,SRC,AKT1,and TP53.

Objective To construct a mindfulness-based self-care intervention program for patients with chronic heart failure(CHF)and their caregivers based on binary disease management theory and explore its small-scale application effect.Methods A prospective study was conducted on 100 pairs of CHF patients admitted to our hospital and their caregivers from January 2024 to October 2024.After excluding those with invalid survey data,92 pairs were finally included and randomly divided into an observation group and a control group,each consisting of 46 pairs.The control group received routine nursing care,while the observation group received the mindfulness-based self-care program based on binary disease management theory in addition to routine nursing care.The Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),Self Compassion Scale(SCS),and Mindfulness Attention Awareness Scale(MAAS)were used to compare the anxiety,depression,self-care,and mindfulness levels of patients and caregivers at three time points:pre-intervention(T1),right post-intervention(T2),and one month post-intervention(T3).The Caregiver Positive Perception Scale(PAC)was used to evaluate the caregiver's positive perception at each time point.Results The HAMA and HAMD scores of patients and caregivers in the observation group were lower than those in the control group at T2 and T3,while the SCS scores were signifi-cantly higher(all P<0.05).Repeated-measures analysis of variance showed significant differences in HAMA,The mindfulness-based self-care intervention program based on binary disease management theory effectively reduces negative emotions in patients and caregivers,and improves mindfulness and self-care,showing clinical application potential.

Objective To investigate the regulatory effect of Dendrobium nobile Lindl alkaloids(DNLA)on the proliferation,migration,and epithelial-mesenchymal transition(EMT)of HLEB3 cells induced by TGF-β2.Methods HLEB3 cells were cultivated in vitro and classified into the control group(DZ),the model group(TGF-β2),and the treatment group(TGF-β2+DNLA).TGF-β2 induced the EMT process of HLEB3 cells.Changes in cell morphology were observed through an inverted microscope.Cell proliferation,apoptosis,and migration were detected by CCK-8 assay,scratch test,and Transwell assay.The total RNAs of the samples were extracted for transcriptome analysis.Bioinformatics processing was employed to obtain relevant information on gene expression differences at the transcriptional level,biological processes,and related signaling pathways.The Western blot(WB)technique was utilized to detect EMT-related proteins to elucidate the mechanism of action of DNLA on lens epithelial cells.Results The study revealed that 10 μg/ml DNLA was suitable for the growth of HLEB3 cells.After 48 hours of the scratch test,the migration rate of the TGF-β2+DNLA group significantly decreased(P<0.01).The Transwell results indicated that the cell migration ability of the TGF-β2+DNLA group was notably weakened(P<0.05).Through bioinformatics,it was discovered that the prevention and treatment of posterior capsular opacification(PCO)by DNLA might be associated with cell junctions,cytoskeleton construction,and fibronectin binding.The pathogenesis of PCO may be related to multiple signaling pathways,including the TGF-β signaling pathway,TNF signaling pathway,and PI3K-Akt signaling pathway.Simultaneously,DNLA could reduce the expression levels of FNI,Smad2/3,and α-SMA proteins and increase the expression of E-cadherin protein.This indicates that DNLA can alleviate abnormal proliferation,migration,and EMT of lens epithelial cells by enhancing intercellular adhesion junctions and weakening cell migration ability,thereby playing a role in preventing and treating posterior capsular opacification.Conclusions DNLA can significantly inhibit the abnormal proliferation and migration of HLEB3 cells,alleviate the EMT process induced by TGF-β2,and prevent and control the occurrence of posterior capsular opacification and other ocular diseases.The mechanism of action might be related to the intervention of the TGF-β/smad signaling pathway and fibrosis proteins such as ZO-1 and E-cadherin.

Objective To investigate the regulatory effect of Dendrobium nobile Lindl alkaloids(DNLA)on the proliferation,migration,and epithelial-mesenchymal transition(EMT)of HLEB3 cells induced by TGF-β2.Methods HLEB3 cells were cultivated in vitro and classified into the control group(DZ),the model group(TGF-β2),and the treatment group(TGF-β2+DNLA).TGF-β2 induced the EMT process of HLEB3 cells.Changes in cell morphology were observed through an inverted microscope.Cell proliferation,apoptosis,and migration were detected by CCK-8 assay,scratch test,and Transwell assay.The total RNAs of the samples were extracted for transcriptome analysis.Bioinformatics processing was employed to obtain relevant information on gene expression differences at the transcriptional level,biological processes,and related signaling pathways.The Western blot(WB)technique was utilized to detect EMT-related proteins to elucidate the mechanism of action of DNLA on lens epithelial cells.Results The study revealed that 10 μg/ml DNLA was suitable for the growth of HLEB3 cells.After 48 hours of the scratch test,the migration rate of the TGF-β2+DNLA group significantly decreased(P<0.01).The Transwell results indicated that the cell migration ability of the TGF-β2+DNLA group was notably weakened(P<0.05).Through bioinformatics,it was discovered that the prevention and treatment of posterior capsular opacification(PCO)by DNLA might be associated with cell junctions,cytoskeleton construction,and fibronectin binding.The pathogenesis of PCO may be related to multiple signaling pathways,including the TGF-β signaling pathway,TNF signaling pathway,and PI3K-Akt signaling pathway.Simultaneously,DNLA could reduce the expression levels of FNI,Smad2/3,and α-SMA proteins and increase the expression of E-cadherin protein.This indicates that DNLA can alleviate abnormal proliferation,migration,and EMT of lens epithelial cells by enhancing intercellular adhesion junctions and weakening cell migration ability,thereby playing a role in preventing and treating posterior capsular opacification.Conclusions DNLA can significantly inhibit the abnormal proliferation and migration of HLEB3 cells,alleviate the EMT process induced by TGF-β2,and prevent and control the occurrence of posterior capsular opacification and other ocular diseases.The mechanism of action might be related to the intervention of the TGF-β/smad signaling pathway and fibrosis proteins such as ZO-1 and E-cadherin.

Objective To elucidate the molecular mechanisms underlying the effects of Kanggan Mixture(KGM)on key targets in rats with acute lung injury,network pharmacology and in vivo micro-CT experiments were employed.Methods Network pharmacology was utilized to forecast the target genes and principal pathways involved in the intervention of KGM in acute lung injury(ALI).Lipopolysaccharide(LPS)-induced ALI rat models were utilized,and micro-computed tomography(micro-CT)was employed to evaluate the extent of lung injury in vivo.Experiments were conducted to verify the intervention mechanism of KGM on ALI rats.Results The findings revealed that 190 chemical constituents were identified from KGM,and 579 potential targets and 204 pathways associated with KGM's impact on ALI were predicted.The principal components of KGM,such as quercetin,luteolin,kaempferol,betulin,and lupenone,exhibit anti-viral,anti-inflammatory,and immunomodulatory properties by targeting TP53,AKT1,SRC,EP300,and STAT3,and modulating the FoxO signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,demonstrating an influence on acute lung injury.Micro-CT results suggest that KGM can improve lung texture enhancement and lung injury in ALI rats,with an increase in end-expiratory lung volume(inspiratory phase-expiratory phase).The HE and W/D ratio results indicate that KGM can improve lung tissue injury and reduce the lung tissue wet/dry weight ratio(P<0.01).Blood cell analysis results show that the anti-inflammatory agent can decrease the WBC(white blood cell count)and N%(neutrophil percentage)in ALI rats'blood(P<0.01),and increase lymphocytes(P<0.05).Real-time quantitative PCR,WES,and immunohistochemistry results suggest that KGM can decrease the mRNA expression,protein distribution,and protein expression levels of TP53,AKT1,SRC,EP300,and STAT3 in lung tissue of ALI rats(P<0.05).Conclusion KGM has a certain intervention effect on acute lung injury,mainly achieved through the core targets STAT3,EP300,SRC,AKT1,and TP53.

As people's living standards improve， the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B （NF-κB） in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors， so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer， and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine （TCM） treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad， it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation， oxidative stress， and energy metabolism， and it is involved in mediating inflammation， pancreatic β cell apoptosis， insulin signal transduction， and other physiological functions. Therefore， blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present， Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections， but the adverse reactions are obvious. TCM has been characterized by multi-target， extensive action， and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation， regulating qi and eliminating phlegm， clearing heat and detoxifying， and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper， the association between NF-κB signaling pathway and diabetes was summarized， and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed， so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice ; Animals ; Adipose Tissue, Brown ; Sirtuin 1/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Morus/metabolism* ; Flavonoids/metabolism* ; Prospective Studies ; Signal Transduction ; Adipose Tissue, White ; Plant Leaves ; Uncoupling Protein 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*