ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndromes in intrahepatic cholestasis of pregnancy （ICP） and its association with perinatal outcomes， and to provide a basis for precise treatment based on TCM syndrome differentiation. MethodsA cross-sectional study was conducted among 275 patients with ICP who were admitted to The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from April 2023 to April 2025. A hierarchical cluster analysis was used to summarize TCM syndromes. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. A multivariate Logistic regression analysis was used to identify the clinical features significantly associated with TCM syndrome. ResultsThe cluster analysis identified three core TCM syndromes among the 275 patients with ICP， i.e.， liver-gallbladder damp-heat syndrome （45.8%）， syndrome of blood deficiency generating wind （30.9%）， and liver depression and spleen deficiency syndrome （23.3%）. There was a significant difference in the distribution of TCM syndromes between different groups stratified by maternal age at delivery， parity， history of ICP recurrence， gestational weeks at disease onset， total bile acid （TBA）， alanine aminotransferase （ALT）， and comorbidity with gestational diabetes mellitus （GDM） （all P<0.05）. The multivariate Logistic regression analysis showed that<34 gestational weeks at disease onset was significantly associated with all three syndromes （damp-heat： odds ratio ［OR］=3.769， P<0.001； blood deficiency： OR=4.031， P<0.001； liver stagnation： OR=3.552， P<0.001）. Liver-gallbladder damp-heat syndrome was associated with maternal age ≥35 years at disease onset （OR=2.048， P=0.014）， parity ≥2 times （OR=1.921， P=0.034）， history of ICP recurrence （OR=2.404， P=0.030）， ALT ≥200 U/L （OR=2.051， P=0.018）， comorbidity with GDM （OR=1.944， P=0.029）， and TBA ≥40 μmol/L （OR=2.542， P=0.024）. The syndrome of blood deficiency generating wind syndrome was associated with maternal age ≥35 years （OR=2.939， P=0.003）， parity ≥2 time （OR=3.222， P=0.003）， history of ICP recurrence （OR=3.809， P=0.010）， ALT ≥200 U/L （OR=2.889， P=0.006）， comorbidity with GDM （OR=3.711， P=0.001）， and comorbidity with hypertensive disorders of pregnancy （OR=4.472， P=0.011）. Liver depression and spleen deficiency syndrome was associated with TBA ≥40 μmol/L （OR=2.995， P=0.044）. The analysis of perinatal outcomes showed that there were significant differences in mode of delivery， gestational weeks at the time of delivery， postpartum blood loss， and neonatal birth weight between the three groups with different TCM syndromes （all P<0.05）. ConclusionLiver-gallbladder damp-heat syndrome， syndrome of blood deficiency generating wind， and liver depression and spleen deficiency syndrome are the main TCM syndrome types in ICP， and the distribution of TCM syndromes is closely associated with clinical factors and perinatal outcomes， which provides a basis for precise TCM syndrome differentiation and individualized treatment.

Objective:To explore the biological efficacy and molecular mechanism of the new 6449Da active peptide against gastric adenocarcinoma.Methods:Effect 6449Da active peptides on SGC-7901 gastric adenocarcinoma cells line was studied and mRNA and protein expression levels of key factors relating to apoptosis, proliferation and notch signaling pathway was detcted.Results:The 6449Da functional fragment WSGC peptide located on the cell membrane relatively specifically inhibited the growth of gastric adenocarcinoma cells, but had a weak effect on normal gastric mucosal cells [cell doubling time , SGC-7901, 1.2 μmol/ml: (38.22±6.80) h vs. 0 μmol/ml: (25.65±1.82) h, P<0.05; GES-1, 1.2 μmol/ml: (33.37±3.15) h vs. 0 μmol/ml: (29.25±1.26) h, P>0.05].After treatment of SGC-7901 cells by IC80 (48 h),the cell apoptosis rate was higher than that in the control group (IC80: 0.421±0.036 vs. control group: 0.028±0.004, P<0.001), while the cell proliferation coefficient,number of transmembrane invasive cells and relative migration rate were all lower than those of the control group (all P<0.01).Compared with the control group, the mRNA and protein expression levels of Bax and Caspase-3 were higher than those in the control group(all P<0.01).Compared with the control group, the mRNA and protein expression levels of Ki67, PCNA, NOTCH1,Jagged 1, MAML3, CSL and HES1 were significantly lower than those in the control group (all P<0.01).After treatment with WSGC bioactive peptides, tumor weight was significantly lower than that of the control group [40 nmol/g: (0.463±0.031) g, 80 nmol/g: (0.340±0.040) g vs. control group: (1.667±0.373) g, all P<0.01]. Conclusion:6449Da functional fragment WSGC active peptide relatively specifically interferes with the growth of gastric adenocarcinoma cells by inhibiting the Notch signaling pathway, and has the biological effects of promoting apoptosis,inhibiting proliferation, transmembrane invasion and migration.

Objective To explore the mechanism of Huanglian Ganjiang Decoction in regulating the mitochondrial apoptotic pathway through the NF-κB/CXCL1/CXCR2 pathway in ulcerative colitis(UC).Methods Sixty C57BL/6J mice were divided into normal group,model group,Huanglian Ganzhang Decoction groups(low,medium and high doses)and mesalazine group.Except for the normal group,UC models were established in the other groups.The general conditions of the mice of all groups were recorded.HE staining was used to observe the pathological changes of the colon and rectum;electron microscopy was used to observe the mitochondrial condition;ELISA was used to determine the contents of IL-6,IL-10,D-lactic acid and DAO;Real-time PCR was used to detect the mRNA expression of NF-κB p65,CXCL1,CXCR2,Bcl-2 and Bax;Western blot was used to determine the protein expression levels of NF-κB p65,CXCL1,CXCR2,p-JAK2,p-STAT3,Bcl-2 and Bax.Results Compared with the normal group,the model group of mice showed a decline in condition,shortened length of the colon and rectum,and mitochondrial structural damage,furthermore,the levels of IL-6,DAO and D-lactic acid were increased,IL-10 level was decreased,the mRNA expression of NF-κB p65,CXCL1,CXCR2 and Bax were enhanced,Bcl-2 mRNA expression was weakened,the protein expression of NF-κB p65,CXCL1,CXCR2,p-JAK2,p-STAT3 and Bax were enhanced,Bcl-2 protein expression was weakened.Compared with the model group,the indexes mentioned above were reversed in the drug groups,especially in the high-dose group.Conclusion Huanglian Ganjiang Decoction may exert its therapeutic effect on UC in mice by regulating the NF-κB/CXCL1/CXCR2 pathway and mitochondrial apoptotic pathway.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective:To explore the repair mechanism of bone marrow stromal cells(BMSCs)transfected with miR-21 in rat sciatic nerve injuries.Methods:In vitro,rat BMSCs were transfected with miR-21 agonist(agomir-21)or blocker(antagomir-21)and their respective empty vectors,respectively,and divided into Control group,agomir-21 group,agomir-NC group,antagomir-21 group and antagomir-NC group.A 12 mm rat sciatic nerve injury model contai-ning decellularized nerve area was prepared,and the cells in each group were labeled with Hoechst33342 for postopera-tive implantation of decellularized nerve area.At 14 d after operation,the recovery of neuromotor function was evaluated by footprint test and the wet weight ratio of gastrocnemius.Immunofluorescence staining was applied to detect the expression of neurofilament protein 200(NF200),myelin basic protein(MBP),S100 calcium binding protein β(S100β)and glial fibrillary acidic protein(GFAP)within the regenerating nerve.Results:Compared with Control group,the sciatic nerve function index(SFI)and the wet weight ratio of gastrocnemius were significantly increased in agomir-21 group(P<0.05);and the density of regenerated nerve fibers and the expression of myelin marker proteins were increased,and the differentiation rate of BMSCs into Schwann cell-like cells(SCLCs)was elevated significantly(P<0.05).Conclusion:miR-21 significantly promotes peripheral nerve regeneration by enhancing the differentiation of BMSCs into SCLCs in vivo.

Objective To explore the mechanism of Huanglian Ganjiang Decoction in regulating the mitochondrial apoptotic pathway through the NF-κB/CXCL1/CXCR2 pathway in ulcerative colitis(UC).Methods Sixty C57BL/6J mice were divided into normal group,model group,Huanglian Ganzhang Decoction groups(low,medium and high doses)and mesalazine group.Except for the normal group,UC models were established in the other groups.The general conditions of the mice of all groups were recorded.HE staining was used to observe the pathological changes of the colon and rectum;electron microscopy was used to observe the mitochondrial condition;ELISA was used to determine the contents of IL-6,IL-10,D-lactic acid and DAO;Real-time PCR was used to detect the mRNA expression of NF-κB p65,CXCL1,CXCR2,Bcl-2 and Bax;Western blot was used to determine the protein expression levels of NF-κB p65,CXCL1,CXCR2,p-JAK2,p-STAT3,Bcl-2 and Bax.Results Compared with the normal group,the model group of mice showed a decline in condition,shortened length of the colon and rectum,and mitochondrial structural damage,furthermore,the levels of IL-6,DAO and D-lactic acid were increased,IL-10 level was decreased,the mRNA expression of NF-κB p65,CXCL1,CXCR2 and Bax were enhanced,Bcl-2 mRNA expression was weakened,the protein expression of NF-κB p65,CXCL1,CXCR2,p-JAK2,p-STAT3 and Bax were enhanced,Bcl-2 protein expression was weakened.Compared with the model group,the indexes mentioned above were reversed in the drug groups,especially in the high-dose group.Conclusion Huanglian Ganjiang Decoction may exert its therapeutic effect on UC in mice by regulating the NF-κB/CXCL1/CXCR2 pathway and mitochondrial apoptotic pathway.

Objective:To explore the repair mechanism of bone marrow stromal cells(BMSCs)transfected with miR-21 in rat sciatic nerve injuries.Methods:In vitro,rat BMSCs were transfected with miR-21 agonist(agomir-21)or blocker(antagomir-21)and their respective empty vectors,respectively,and divided into Control group,agomir-21 group,agomir-NC group,antagomir-21 group and antagomir-NC group.A 12 mm rat sciatic nerve injury model contai-ning decellularized nerve area was prepared,and the cells in each group were labeled with Hoechst33342 for postopera-tive implantation of decellularized nerve area.At 14 d after operation,the recovery of neuromotor function was evaluated by footprint test and the wet weight ratio of gastrocnemius.Immunofluorescence staining was applied to detect the expression of neurofilament protein 200(NF200),myelin basic protein(MBP),S100 calcium binding protein β(S100β)and glial fibrillary acidic protein(GFAP)within the regenerating nerve.Results:Compared with Control group,the sciatic nerve function index(SFI)and the wet weight ratio of gastrocnemius were significantly increased in agomir-21 group(P<0.05);and the density of regenerated nerve fibers and the expression of myelin marker proteins were increased,and the differentiation rate of BMSCs into Schwann cell-like cells(SCLCs)was elevated significantly(P<0.05).Conclusion:miR-21 significantly promotes peripheral nerve regeneration by enhancing the differentiation of BMSCs into SCLCs in vivo.

Objective:To explore the biological efficacy and molecular mechanism of the new 6449Da active peptide against gastric adenocarcinoma.Methods:Effect 6449Da active peptides on SGC-7901 gastric adenocarcinoma cells line was studied and mRNA and protein expression levels of key factors relating to apoptosis, proliferation and notch signaling pathway was detcted.Results:The 6449Da functional fragment WSGC peptide located on the cell membrane relatively specifically inhibited the growth of gastric adenocarcinoma cells, but had a weak effect on normal gastric mucosal cells [cell doubling time , SGC-7901, 1.2 μmol/ml: (38.22±6.80) h vs. 0 μmol/ml: (25.65±1.82) h, P<0.05; GES-1, 1.2 μmol/ml: (33.37±3.15) h vs. 0 μmol/ml: (29.25±1.26) h, P>0.05].After treatment of SGC-7901 cells by IC80 (48 h),the cell apoptosis rate was higher than that in the control group (IC80: 0.421±0.036 vs. control group: 0.028±0.004, P<0.001), while the cell proliferation coefficient,number of transmembrane invasive cells and relative migration rate were all lower than those of the control group (all P<0.01).Compared with the control group, the mRNA and protein expression levels of Bax and Caspase-3 were higher than those in the control group(all P<0.01).Compared with the control group, the mRNA and protein expression levels of Ki67, PCNA, NOTCH1,Jagged 1, MAML3, CSL and HES1 were significantly lower than those in the control group (all P<0.01).After treatment with WSGC bioactive peptides, tumor weight was significantly lower than that of the control group [40 nmol/g: (0.463±0.031) g, 80 nmol/g: (0.340±0.040) g vs. control group: (1.667±0.373) g, all P<0.01]. Conclusion:6449Da functional fragment WSGC active peptide relatively specifically interferes with the growth of gastric adenocarcinoma cells by inhibiting the Notch signaling pathway, and has the biological effects of promoting apoptosis,inhibiting proliferation, transmembrane invasion and migration.