Metastasis in gastric cancer is a key factor contributing to poor prognosis. Its pathogenesis is complex， characterized by a combination of underlying deficiency and superficial excess， cold and heat in complexity， and stagnation in collateral Conventional aggressive treatment methods tend to exacerbate the depletion of healthy Qi and Zang-Fu organ dysfunctions. The harmonizing method in traditional Chinese medicine （TCM） emphasizes holistic regulation and reinforcing healthy Qi while expelling pathogenic factors. The blood harmonizing method is grounded in the core TCM theory of blood vessel transmission and Zang-Fu organ accumulation of cancerous toxins. It closely addresses the essence of metastasis-where cancerous toxins spread through the bloodstream and accumulate in the collaterals-thereby providing a unique and feasible diagnostic and therapeutic approach for clinical intervention in gastric cancer metastasis. This paper systematically reviews relevant TCM theories such as transmission and Zang-Fu organ accumulation of cancerous toxins and accumulation-gathering and provides an in-depth explanation of the core pathogenesis of gastric cancer metastasis. Specifically， cancerous toxins circulate throughout the body via the blood vessels and accumulate in the collaterals of target organs such as the liver， peritoneum， lymph nodes， and lungs. The occurrence and development of this process are consistently centered on the key mechanism of disharmony in blood-related syndromes. On this basis， the paper explicitly proposes three major therapeutic approaches centered on harmonizing the blood. The first is harmonizing the blood to restore ascending and descending functions， thereby invigorating the spleen and regulating the middle energizer to restore the mediating function of the middle energizer and block the generation of phlegm and blood stasis at the root. The second is harmonizing the blood to balance cold and heat， using pungent herbs to open and bitter herbs to descend to harmonize the Yin-Yang balance and improve the homeostasis of the tumor microenvironment. The third is harmonizing the blood to unblock collaterals and resolve stasis， thereby gradually dissipating stasis and nodules， gently clearing obstructions in the collaterals， and breaking the critical link of collateral stagnation forming masses caused by metastasis. The article further summarizes modern pharmacological research findings on representative formulas such as Banxia Xiexintang， Weichang'an， Yangzheng Sanjie decoction， and Sijunzitang， confirming that they can inhibit the proliferation， invasion， and metastasis of gastric cancer cells， as well as epithelial-mesenchymal transition， through multiple targets and pathways， to regulate angiogenesis and lymphangiogenesis， modulate the immune microenvironment， and induce tumor cell apoptosis and ferroptosis， thereby blocking the metastasis process at multiple levels. This paper discusses the theoretical basis， pathogenetic mechanisms， therapeutic systems， and modern mechanisms of the blood harmonizing method for the diagnosis and treatment of gastric cancer metastasis. It fully embodies the TCM principles of targeting balance， reinforcing healthy Qi without aiding the pathogen， and eliminating the pathogen without harming the healthy Qi， providing a solid theoretical foundation and practical pharmacological references for the prevention and treatment of gastric cancer metastasis with integrated traditional Chinese and Western medicine in clinical practice.

ObjectiveTo investigate the synergistic promotion of malignant phenotypes in gastric cancer cells by tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs） and polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） through crosstalk， and the intervention mechanism of the intestinal absorption solution containing Banxia Xiexintang （BXT）. MethodsGastric cancer MFC cells were treated with conditioned medium （co-culture-CM） prepared from a co-culture system of TA-BMSCs and PMN-MDSCs. Groups included control， co-culture-CM model， stromal cell-derived factor 1 （SDF1） inhibitor （LY2510924）， α₄β₁ inhibitor （BIO5192）， dual inhibitor combination， and different concentrations （55%， 70%， 85%） of BXT-containing intestinal absorption solutions. MFC cell proliferation， migration， invasion， and apoptosis were assessed via cell counting kit-8 （CCK-8） assay， wound-healing assay， Transwell assay， and flow cytometry. The SDF-1， α₄β₁， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA） levels in culture supernatants， along with the protein levels of intracellular macrophage migration inhibitory factor （MIF）， chemokine （C-X-C motif） receptor 4 （CXCR4）， CD106， MMP-9， and VEGFA in MFC cells， were measured by enzyme-linked immunosorbent assay （ELISA） and Western blot， respectively. ResultsCompared with the control group， co-culture-CM promoted the proliferation， migration， and invasion of MFC cells （P<0.01）， elevated the levels of SDF-1， α₄β₁， MMP-9， and VEGFA （P<0.01）， and upregulated the protein levels of MIF （P<0.05）， MMP-9 （P<0.01）， and VEGFA （P<0.01）. Compared with co-culture-CM， BXT-containing intestinal absorption solutions at various concentrations significantly reversed the phenotypic effects on cells， inhibited malignant phenotypes， lowered the levels of MMP-9 and SDF1， and reduced the expression of proteins in the crosstalk axis. Compared with the SDF1+α₄β₁ inhibitor group， the SDF1 inhibitor group and the α₄β₁ inhibitor group showed no differences in the inhibition of proliferation， scratch healing， and cytokine levels. The SDF1 inhibitor increased the apoptosis rate and downregulated the protein levels of MIF and CD106， while the α₄β₁ inhibitor increased the number of migrated cells and the expression of various proteins. Compared with the SDF1 inhibitor group， the α₄β₁ inhibitor group showed reduced inhibitory effect on proliferation， decreased apoptosis rate， increased number of invasive cells， decreased α₄β₁ content， and increased expression of various proteins （P<0.01）. The 55%， 70%， and 85% intestinal absorption solutions increased the inhibitory effect on proliferation， decreased the number of invasive cells， and increased the apoptosis rate （P<0.01）. The 55% BXT-containing intestinal absorption solution group showed increased wound healing rate and upregulated protein levels of VEGFA， CD106， and MMP-9 （P<0.05）. The 70% intestinal absorption solution group showed upregulated protein level of MIF （P<0.05）， and the 85% intestinal absorption solution group showed upregulated protein level of VEGFA （P<0.01） and downregulated the protein level of CXCR4 （P<0.01）. ConclusionTA-BMSCs and PMN-MDSCs synergistically activate the MIF/SDF-1/CXCR4 and MMP-9/α₄β₁/CD106 axes through crosstalk， significantly enhancing gastric cancer cell invasion and migration. BXT-containing intestinal absorption fluid effectively inhibits the malignant progression of gastric cancer cells by multi-targeted intervention in this crosstalk process.

ObjectiveTo explore whether the intestinal absorption solution containing Banxia Xiexintang （BXT） can inhibit the invasion and migration of gastric cancer cells by interfering with the stromal cell-derived factor 1 （SDF1）-CXC chemokine receptor 4 （CXCR4） axis in tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs）. MethodsThe intestinal absorption solution containing BXT was prepared， and the optimal intervention concentration and duration for MFC cells were determined through the cell counting kit-8 （CCK-8） assay. A co-culture system was established comprising TA-BMSCs conditioned medium （TA-BMSCs-CM） and gastric cancer MFC cells. The experiment was conducted with a blank control group， a TA-BMSCs-CM group， an SDF1 inhibitor （LY2510924） group， and intervention groups with varying concentrations （55%， 70%， 85%） of the intestinal absorption solution containing BXT. Cell proliferation was assessed by the CCK-8 assay. Horizontal and vertical cell migration were evaluated via scratch and Transwell assays， respectively. Cell invasion was examined by a Transwell assay with Matrigel. Cell apoptosis was detected by flow cytometry. The levels of factors such as SDF1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）， as well as the protein levels of macrophage migration inhibitory factor （MIF）， CXCR4， VEGFA， and MMP-9， were quantified by ELISA and Western blot， respectively. ResultsThe CCK-8 assay results indicated that compared with the 24 h intervention， the 48 h interventions with all concentrations of the intestinal absorption solution containing BXT increased the inhibition rate on MFC cells （P<0.01）. The half-maximal inhibitory concentration （IC₅₀） of the intestinal absorption solution containing BXT at the time point of 48 h was 68.51%， and subsequent intervention concentrations were selected as 55%， 70%， and 85%. Compared with the TA-BMSCs-CM group， the intestinal absorption solution containing BXT （particularly at concentrations of 70% 85%） suppressed the proliferation， migration， and invasion of MFC cells， promoted the cell apoptosis （P<0.05， P<0.01）， decreased the levels of SDF1， MMP-9， and VEGFA， and downregulated the protein levels of MIF， CXCR4， VEGFA， and MMP-9 （P<0.05， P<0.01）. The inhibitory effects of the intestinal absorption solution containing BXT were comparable to or superior to those of the SDF1 inhibitor （P<0.01）. ConclusionThe intestinal absorption solution containing BXT can inhibit the invasion and migration of gastric cancer cells by interfering with the SDF1-CXCR4 axis in TA-BMSCs. The underlying mechanism may involve the regulation of the MIF/SDF1/CXCR4 signaling pathway and its downstream effector molecules.

ObjectiveTo observe how Banxia Xiexintang affects programmed cell death 1 ligand 1 （PD-L1） expression induced by exosomes derived from gastric cancer cells in bone marrow mesenchymal stem cells （BMSCs） through the protein kinase B （Akt）/c-myelocytomatosis oncogene （c-Myc） signaling axis， and its effects on the migration of BMSCs and gastric cancer cells. MethodsExosomes were isolated from human gastric cancer NCI-N87 cells and identified by transmission electron microscopy and Western blot. Rat BMSCs were passaged and identified by immunofluorescence staining. A Transwell chamber was used to create a non-contact co-culture system for NCI-N87 exosomes and BMSCs. The experiment was designed with normal， model， Banxia Xiexintang （10% serum containing Banxia Xiexintang）， PD-L1 monoclonal antibody （10% blank serum containing PD-L1 antibody）， and combination （10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody） groups. The suspension of BMSCs was added to the upper chamber of each group， with the normal group receiving serum culture medium without exosomes in the lower chamber， and the model group receiving NCI-N87 exosomes. The Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group received 10% serum containing Banxia Xiexintang， 10% blank serum containing PD-L1 monoclonal antibody， and 10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody， respectively， in the upper chamber. After 96 h， BMSCs from the upper chamber were collected， and the protein levels of p-Akt， Akt， c-Myc， and PD-L1， as well as the mRNA levels of Akt， c-Myc， and PD-L1， were determined by Western blot and Real-time PCR， respectively. The migration of BMSCs and NCI-N87 was assessed by the Transwell method. ResultsCompared with the normal group， the model group showed increases in protein levels of p-Akt， c-Myc， and PD-L1， as well as mRNA levels of c-Myc and PD-L1 （P<0.05， P<0.01）， and no significant change in the protein and mRNA levels of Akt. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in protein levels of p-Akt， c-Myc， and PD-L1 （P<0.01）. In addition， they had significant effects on the protein and mRNA levels of Akt. The combination group showed greater reductions in the protein and mRNA levels of c-Myc and PD-L1 than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.05）. Compared with the normal group， the model group showed increases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）， with the combination group showing greater reductions in the number of migrating NCI-N87 and BMSCs than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.01）. ConclusionBanxia Xiexintang can lower the PD-L1 expression induced by gastric cancer cell-derived exosomes in BMSCs induced and inhibit the migration of BMSCs and gastric cancer cells. Moreover， it has a synergistic effect when being used together with PD-L1， possibly related to the regulation of the Akt/c-Myc signaling axis.

Metastasis in gastric cancer is a key factor contributing to poor prognosis. Its pathogenesis is complex， characterized by a combination of underlying deficiency and superficial excess， cold and heat in complexity， and stagnation in collateral Conventional aggressive treatment methods tend to exacerbate the depletion of healthy Qi and Zang-Fu organ dysfunctions. The harmonizing method in traditional Chinese medicine （TCM） emphasizes holistic regulation and reinforcing healthy Qi while expelling pathogenic factors. The blood harmonizing method is grounded in the core TCM theory of blood vessel transmission and Zang-Fu organ accumulation of cancerous toxins. It closely addresses the essence of metastasis-where cancerous toxins spread through the bloodstream and accumulate in the collaterals-thereby providing a unique and feasible diagnostic and therapeutic approach for clinical intervention in gastric cancer metastasis. This paper systematically reviews relevant TCM theories such as transmission and Zang-Fu organ accumulation of cancerous toxins and accumulation-gathering and provides an in-depth explanation of the core pathogenesis of gastric cancer metastasis. Specifically， cancerous toxins circulate throughout the body via the blood vessels and accumulate in the collaterals of target organs such as the liver， peritoneum， lymph nodes， and lungs. The occurrence and development of this process are consistently centered on the key mechanism of disharmony in blood-related syndromes. On this basis， the paper explicitly proposes three major therapeutic approaches centered on harmonizing the blood. The first is harmonizing the blood to restore ascending and descending functions， thereby invigorating the spleen and regulating the middle energizer to restore the mediating function of the middle energizer and block the generation of phlegm and blood stasis at the root. The second is harmonizing the blood to balance cold and heat， using pungent herbs to open and bitter herbs to descend to harmonize the Yin-Yang balance and improve the homeostasis of the tumor microenvironment. The third is harmonizing the blood to unblock collaterals and resolve stasis， thereby gradually dissipating stasis and nodules， gently clearing obstructions in the collaterals， and breaking the critical link of collateral stagnation forming masses caused by metastasis. The article further summarizes modern pharmacological research findings on representative formulas such as Banxia Xiexintang， Weichang'an， Yangzheng Sanjie decoction， and Sijunzitang， confirming that they can inhibit the proliferation， invasion， and metastasis of gastric cancer cells， as well as epithelial-mesenchymal transition， through multiple targets and pathways， to regulate angiogenesis and lymphangiogenesis， modulate the immune microenvironment， and induce tumor cell apoptosis and ferroptosis， thereby blocking the metastasis process at multiple levels. This paper discusses the theoretical basis， pathogenetic mechanisms， therapeutic systems， and modern mechanisms of the blood harmonizing method for the diagnosis and treatment of gastric cancer metastasis. It fully embodies the TCM principles of targeting balance， reinforcing healthy Qi without aiding the pathogen， and eliminating the pathogen without harming the healthy Qi， providing a solid theoretical foundation and practical pharmacological references for the prevention and treatment of gastric cancer metastasis with integrated traditional Chinese and Western medicine in clinical practice.

ObjectiveTo investigate the synergistic promotion of malignant phenotypes in gastric cancer cells by tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs） and polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） through crosstalk， and the intervention mechanism of the intestinal absorption solution containing Banxia Xiexintang （BXT）. MethodsGastric cancer MFC cells were treated with conditioned medium （co-culture-CM） prepared from a co-culture system of TA-BMSCs and PMN-MDSCs. Groups included control， co-culture-CM model， stromal cell-derived factor 1 （SDF1） inhibitor （LY2510924）， α₄β₁ inhibitor （BIO5192）， dual inhibitor combination， and different concentrations （55%， 70%， 85%） of BXT-containing intestinal absorption solutions. MFC cell proliferation， migration， invasion， and apoptosis were assessed via cell counting kit-8 （CCK-8） assay， wound-healing assay， Transwell assay， and flow cytometry. The SDF-1， α₄β₁， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA） levels in culture supernatants， along with the protein levels of intracellular macrophage migration inhibitory factor （MIF）， chemokine （C-X-C motif） receptor 4 （CXCR4）， CD106， MMP-9， and VEGFA in MFC cells， were measured by enzyme-linked immunosorbent assay （ELISA） and Western blot， respectively. ResultsCompared with the control group， co-culture-CM promoted the proliferation， migration， and invasion of MFC cells （P<0.01）， elevated the levels of SDF-1， α₄β₁， MMP-9， and VEGFA （P<0.01）， and upregulated the protein levels of MIF （P<0.05）， MMP-9 （P<0.01）， and VEGFA （P<0.01）. Compared with co-culture-CM， BXT-containing intestinal absorption solutions at various concentrations significantly reversed the phenotypic effects on cells， inhibited malignant phenotypes， lowered the levels of MMP-9 and SDF1， and reduced the expression of proteins in the crosstalk axis. Compared with the SDF1+α₄β₁ inhibitor group， the SDF1 inhibitor group and the α₄β₁ inhibitor group showed no differences in the inhibition of proliferation， scratch healing， and cytokine levels. The SDF1 inhibitor increased the apoptosis rate and downregulated the protein levels of MIF and CD106， while the α₄β₁ inhibitor increased the number of migrated cells and the expression of various proteins. Compared with the SDF1 inhibitor group， the α₄β₁ inhibitor group showed reduced inhibitory effect on proliferation， decreased apoptosis rate， increased number of invasive cells， decreased α₄β₁ content， and increased expression of various proteins （P<0.01）. The 55%， 70%， and 85% intestinal absorption solutions increased the inhibitory effect on proliferation， decreased the number of invasive cells， and increased the apoptosis rate （P<0.01）. The 55% BXT-containing intestinal absorption solution group showed increased wound healing rate and upregulated protein levels of VEGFA， CD106， and MMP-9 （P<0.05）. The 70% intestinal absorption solution group showed upregulated protein level of MIF （P<0.05）， and the 85% intestinal absorption solution group showed upregulated protein level of VEGFA （P<0.01） and downregulated the protein level of CXCR4 （P<0.01）. ConclusionTA-BMSCs and PMN-MDSCs synergistically activate the MIF/SDF-1/CXCR4 and MMP-9/α₄β₁/CD106 axes through crosstalk， significantly enhancing gastric cancer cell invasion and migration. BXT-containing intestinal absorption fluid effectively inhibits the malignant progression of gastric cancer cells by multi-targeted intervention in this crosstalk process.

ObjectiveTo explore whether the intestinal absorption solution containing Banxia Xiexintang （BXT） can inhibit the invasion and migration of gastric cancer cells by interfering with the stromal cell-derived factor 1 （SDF1）-CXC chemokine receptor 4 （CXCR4） axis in tumor-associated bone marrow mesenchymal stem cells （TA-BMSCs）. MethodsThe intestinal absorption solution containing BXT was prepared， and the optimal intervention concentration and duration for MFC cells were determined through the cell counting kit-8 （CCK-8） assay. A co-culture system was established comprising TA-BMSCs conditioned medium （TA-BMSCs-CM） and gastric cancer MFC cells. The experiment was conducted with a blank control group， a TA-BMSCs-CM group， an SDF1 inhibitor （LY2510924） group， and intervention groups with varying concentrations （55%， 70%， 85%） of the intestinal absorption solution containing BXT. Cell proliferation was assessed by the CCK-8 assay. Horizontal and vertical cell migration were evaluated via scratch and Transwell assays， respectively. Cell invasion was examined by a Transwell assay with Matrigel. Cell apoptosis was detected by flow cytometry. The levels of factors such as SDF1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor A （VEGFA）， as well as the protein levels of macrophage migration inhibitory factor （MIF）， CXCR4， VEGFA， and MMP-9， were quantified by ELISA and Western blot， respectively. ResultsThe CCK-8 assay results indicated that compared with the 24 h intervention， the 48 h interventions with all concentrations of the intestinal absorption solution containing BXT increased the inhibition rate on MFC cells （P<0.01）. The half-maximal inhibitory concentration （IC₅₀） of the intestinal absorption solution containing BXT at the time point of 48 h was 68.51%， and subsequent intervention concentrations were selected as 55%， 70%， and 85%. Compared with the TA-BMSCs-CM group， the intestinal absorption solution containing BXT （particularly at concentrations of 70% 85%） suppressed the proliferation， migration， and invasion of MFC cells， promoted the cell apoptosis （P<0.05， P<0.01）， decreased the levels of SDF1， MMP-9， and VEGFA， and downregulated the protein levels of MIF， CXCR4， VEGFA， and MMP-9 （P<0.05， P<0.01）. The inhibitory effects of the intestinal absorption solution containing BXT were comparable to or superior to those of the SDF1 inhibitor （P<0.01）. ConclusionThe intestinal absorption solution containing BXT can inhibit the invasion and migration of gastric cancer cells by interfering with the SDF1-CXCR4 axis in TA-BMSCs. The underlying mechanism may involve the regulation of the MIF/SDF1/CXCR4 signaling pathway and its downstream effector molecules.

ObjectiveTo observe how Banxia Xiexintang affects programmed cell death 1 ligand 1 （PD-L1） expression induced by exosomes derived from gastric cancer cells in bone marrow mesenchymal stem cells （BMSCs） through the protein kinase B （Akt）/c-myelocytomatosis oncogene （c-Myc） signaling axis， and its effects on the migration of BMSCs and gastric cancer cells. MethodsExosomes were isolated from human gastric cancer NCI-N87 cells and identified by transmission electron microscopy and Western blot. Rat BMSCs were passaged and identified by immunofluorescence staining. A Transwell chamber was used to create a non-contact co-culture system for NCI-N87 exosomes and BMSCs. The experiment was designed with normal， model， Banxia Xiexintang （10% serum containing Banxia Xiexintang）， PD-L1 monoclonal antibody （10% blank serum containing PD-L1 antibody）， and combination （10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody） groups. The suspension of BMSCs was added to the upper chamber of each group， with the normal group receiving serum culture medium without exosomes in the lower chamber， and the model group receiving NCI-N87 exosomes. The Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group received 10% serum containing Banxia Xiexintang， 10% blank serum containing PD-L1 monoclonal antibody， and 10% serum containing Banxia Xiexintang and 10% blank serum containing PD-L1 antibody， respectively， in the upper chamber. After 96 h， BMSCs from the upper chamber were collected， and the protein levels of p-Akt， Akt， c-Myc， and PD-L1， as well as the mRNA levels of Akt， c-Myc， and PD-L1， were determined by Western blot and Real-time PCR， respectively. The migration of BMSCs and NCI-N87 was assessed by the Transwell method. ResultsCompared with the normal group， the model group showed increases in protein levels of p-Akt， c-Myc， and PD-L1， as well as mRNA levels of c-Myc and PD-L1 （P<0.05， P<0.01）， and no significant change in the protein and mRNA levels of Akt. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in protein levels of p-Akt， c-Myc， and PD-L1 （P<0.01）. In addition， they had significant effects on the protein and mRNA levels of Akt. The combination group showed greater reductions in the protein and mRNA levels of c-Myc and PD-L1 than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.05）. Compared with the normal group， the model group showed increases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）. Compared with the model group， the Banxia Xiexintang group， PD-L1 monoclonal antibody group， and combination group showed decreases in the number of migrating NCI-N87 and BMSCs （P<0.05， P<0.01）， with the combination group showing greater reductions in the number of migrating NCI-N87 and BMSCs than the Banxia Xiexintang group and PD-L1 monoclonal antibody group （P<0.01）. ConclusionBanxia Xiexintang can lower the PD-L1 expression induced by gastric cancer cell-derived exosomes in BMSCs induced and inhibit the migration of BMSCs and gastric cancer cells. Moreover， it has a synergistic effect when being used together with PD-L1， possibly related to the regulation of the Akt/c-Myc signaling axis.

Objective To observe the effects of Yifei Jianpi Prescription on airway mucus hypersecretion and protein expressions of EGFR/PKC/NF-κB pathway in lipopolysaccharide(LPS)-induced acute lung injury(ALI)model rats;To explore its mechanism in the treatment of ALI.Methods Ten of 60 SPF SD rats were randomly selected as blank group,and the other rats were intratracheal instilled with LPS to establish ALI model.The model rats were randomly divided into model group,dexamethasone group and Yifei Jianpi Prescription high-,medium-and low-dosage groups,with 8 rats in each group.Each treatment group was given corresponding drug solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 14 days.The pulmonary functions of rats were measured[peak expiratory flow(PEF),tidal volume(TV),expiratory volume(EV),50%expiratory flow rate(EF50)],HE staining was used to observe the morphology of lung tissue,AB-PAS staining was used to evaluate the proliferation and mucus secretion of goblet cells,the expressions of epidermal growth factor receptor(EGFR),protein kinase C(PKC),nuclear factor-κB(NF-κB)p65 and MUC5AC in lung tissue were detected by immunofluorescence staining,the mRNA expressions of EGFR and MUC5AC in lung tissue were detected by fluorescent quantitative PCR,and the content of MUC5AC in lung tissue was detected by ELISA.Results Compared with the blank group,PEF,TV,EV and EF50 of the model group rats significantly decreased(P<0.01);the bronchial wall was significantly thickened,the lumen narrowed,pulmonary interstitial edema and hyperemia,the thickness of alveolar wall increased,accompanied by a large number of inflammatory cells infiltration,and the lung tissue injury score increased significantly(P<0.01);goblet cells proliferated significantly,mucus secretion increased significantly(P<0.01);the protein expressions of EGFR,PKC,NF-κB p65,MUC5AC and mRNA expressions of EGFR and MUC5AC in lung tissue increased significantly(P<0.01),and the content of MUC5AC in lung tissue increased significantly(P<0.01).Compared with the model group,PEF,TV,EV and EF50 in dexamethasone group and Yifei Jianpi Prescription each dosage groups increased in varying degrees;the pathological injury of lung tissue was alleviated to varying degrees,the score of lung tissue injury was reduced;the proliferation of goblet cells was reduced,and the secretion of mucus was reduced,the expressions of EGFR,PKC,NF-κB p65,MUC5AC protein and EGFR,MUC5AC mRNA in lung tissue decreased,and the content of MUC5AC in lung tissue decreased.There was statistical significance in dexamethasone group and Yifei Jianpi Prescription high-and medium-dosage groups(P<0.01).Conclusion Yifei Jianpi Prescription can inhibit the hypersecretion of airway mucus and the high expression of EGFR/PKC/NF-κB pathway protein in rats with ALI induced by LPS.

Objective To identify the risk factors and investigate etiological spectrum of pulmonary fungal infections(PFIs)in patients with end-stage liver disease(ESLD).Methods A retrospective analysis was performed on the clinical data of 211 ESLD patients.Based on pulmonary imaging,clinical manifestations,and microbiological test results,patients were categorized into three groups,including the PFI group(or the case group),the non-fungal pneumonia group(or the control group 1),and the group without pneumonia(or the control group 2).The clinical characteristics of patients in the the case group were then compared with those of patients in the two control groups.Taking patients without pneumonia as the control,univariate and multivariate logistic regression analyses were performed to identify independent risk factors for PFI,and a nomogram prediction model was constructed based on these risk factors.Results Among the 211 patients,76(36.1%)had PFIs,46(21.8%)had non-fungal pneumonia,and 89(42.2%)did not have pneumonia.According to findings from the multivariate logistic regression,elevated white blood cell count upon admission(OR=1.211;95%CI,1.011-1.460),higher Model for End-Stage Liver Disease-Sodium(MELD-Na)score(OR=1.140;95%CI,1.021-1.282),concomitant hepatorenal syndrome(OR=4.150;95%CI,1.050-17.300),cumulative glucocorticoid use for more than seven days(OR=26.832;95%CI,6.361-113.221),and the administration of broad-spectrum antibiotics at the time of hospital admission(OR=6.601;95%CI,1.951-22.362)were identified as independent risk factors for PFI.A predictive nomogram model named TJLFPFI was constructed based on these risk factors.The area under the receiver operating characteristic(AUC)curve of the model was 0.899(95%CI,0.853-0.945).Etiologic analysis of the 76 PFI cases revealed that 36(47.4%)had positive results for culture,while 40(52.6%)had negative results for sputum culture but tested positive by the 1,3-β-D-glucan test and/or galactomannan test.Aspergillus was the most frequently identified pathogen,detected in 25 of the 36 cases(59.5%).Conclusion PFI in ESLD patients is closely associated with disease severity at admission,early use of broad-spectrum antibiotics,and prolonged glucocorticoid therapy.Aspergillus is the predominant pathogen.The TJLFPFI model shows potential value in identifying high-risk patients,but prospective validation is still warranted.