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.

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 investigate the infection of mouse norovirus (MNV) in experimental mice raised under natural conditions from 19 biological companies in Beijing. MethodsThe mice used in this study were randomly selected from mice produced by 19 companies, and 14 mice of each strain and batch were combined into one cage, totaling 1 396 cages of 19 544 mice. The fecal samples from BALB/c, C57BL/6, ICR, KM, and BALB/c-nude mice were collected. TaqMan probe fluorescence quantitative PCR method was used to detect MNV infection of mice with MNV-1 primer, and whether the mice were infected with MNV was determined according to cycle threshold (Ct value). The chi-square test was used to analyze the difference of positive rate among the fecal samples from the five types of mice. The Ct values of the positive samples were statistically described; the non-parametric test was used to analyze the differences in Ct values among the five types of mice. Results A total of 1 396 fecal samples were collected. The positive rates of fecal MNV detection in BALB/c, C57BL/6, ICR, KM, and BALB/c-nude mice were 17.65%, 39.33%, 10.57%, 18.32% and 27.4%, respectively. According to the chi-square test results, the positive rate of fecal in C57BL/6 mice was higher than that in BALB/c, ICR, and KM mice (all P<0.05), and the positive rate of BALB/c-nude mice was higher than that in ICR and BALB/c mice (P<0.001, P＜0.05) . The viral load of BALB/c-nude or C57BL/6 mice was generally greater than that of KM mice (P<0.05). ConclusionMNV-1 primers can be applied to the detection of MNV infection in mice. The positive rate of MNV in five types of experimental mice in Beijing ranges from 10% to 40%, among which C57BL/6 mice and BALB/c-nude mice have higher positive rates of MNV than the others.

Objective:To fit and predict the trend of COVID-19 epidemics in the United States (USA) and the United Kingdom (UK), and analyze the effect of vaccination.Methods:Based on the SEIR dynamic model, considering the presymptomatic infections, isolation measures, vaccine vaccination coverage, etc., we developed a SEIR with vaccine inoculation, Presymptomatic infectious, unconfirmed infectious, hospital isolation and domiciliary isolation dynamics model. The publicly released incidence data of COVID-19 from November 6, 2020 to January 31, 2021 in USA and from November 23, 2020 to January 31, 2021 in UK were used to fit the model and the publicly released incidence data of COVID-19 from February 1, 2021 to April 1 were used to evaluate the predicting power of the model by software R 4.0.3 and predict changes in the daily new cases in the context of different vaccination coverage. Results:According to the cumulative confirmed cases, the fitting bias and the predicting bias of the SVEPIUHDR model for USA and UK were less than 5%, respectively. From the model prediction results, the cumulative cases after COVID-19 vaccination in USA in early April reached 31 864 970. If there had not had such vaccination, the cumulative cases of COVID-19 would have reached to 35 317 082, with a gap of more than 3.4 million cases. In UK, the cumulative cases of COVID-19 after the vaccination was estimated to be 4 195 538 in early April, compared with 4 268 786 cases if no COVID-19 vaccination had been provided, there would have heen a gap of more than 70 000 cases.Conclusion:SVEPIUHDR model shows a good prediction effect on the epidemic of COVID-19 in both USA and UK.

Objective:To explore the correlation between Coronin-1 and non-Mtb induced autophagy in macrophages and its possible signal pathway.Methods: The pEGFP-C1-Coronin-1 plasmids encoding the over-expression of Coronin-1 and pGenesil-1-Coronin-1 plasmids encoding the siRNA of Coronin-1 gene were constructed and transfected into RAW264.7 respectively in order to obtain their stable transfected cell line ( RAW264.7-Cor.Plus and RAW264.7-Cor.Minus ).After the RAW264.7, RAW264.7-Cor.Plus and RAW264.7-Cor.Minus group cells were treated with complete medium, starvation, Rapamycin and Cyclosporine A respectively,the transcription level of Beclin-1 gene was detected by RT-PCR,and the protein expression level of Coronin-1 and Beclin-1 and the ratio of LC3BⅡ/LC3BⅠwas analyzed by Western blot.Results:The over-expression plasmids,the siRNA plasmids and their stable transfected cell lines which can over-express the Coronin-1 or inhibit its expression were successfully constructed.When the three groups cell treated with blank control,the ratio of LC3BⅡ/LC3BⅠwas found that:RAW264.7-Cor.Minus>RAW264.7>RAW264.7-Cor.Plus significantly,and the transcription level of Beclin-1 gene and its protein detected by RT-PCR and Western blot respectively showed the same trend with the ratio of LC3BⅡ/LC3BⅠ;When the three groups cell treated with starvation,the ratio of LC3BⅡ/LC3BⅠjust become the opposite of the first result significantly;When the RAW264.7 cells treated with Rapamycin, the expression of Coronin-1 was inhibited significantly.The ratio of LC3BⅡ/LC3BⅠin the RAW264.7-Cor.Plus group treated with Rapamycin and CsA respectively was higher than its corresponding control treatment group.Conclusion:There is a correlation between Coronin-1 and non-Mtb induced cell autophagy in macrophage.In the nutrition sufficient condition, Coronin-1 can inhibit autophagy;in the hungry condition,Coronin-1 can promote autophagy.The regulation of autophagy by Coronin-1 may be associated with mTOR and calcium signaling pathway.