ObjectiveTo investigate the protective effect of Dabupi Tang （DBPT） against radiation-induced lung injury （RILI） and to elucidate whether its mechanism involves modulating the inflammatory response mediated by the Janus kinase 1 （JAK1）/signal transducer and activator of transcription 6 （STAT6） signaling pathway. MethodsForty-eight SPF-grade male SD rats were randomized into 6 groups （n=8）： blank control， model， high-dose （24.28 g·kg^-1） DBPT， medium-dose （12.14 g·kg^-1） DBPT， low-dose （6.07 g·kg^-1） DBPT， and high-dose DBPT + AG490 （a JAK1/STAT6 inhibitor， 5 mg·kg^-1）. After two consecutive weeks of gavage， other groups except the blank control group received single-dose irradiation with 8 Gy X-ray to the right lung for the modeling of RILI. Samples were collected 24 h post-irradiation. Hematoxylin-eosin （HE） staining was used to observe lung histopathology. Serum levels of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and transforming growth factor-β （TGF-β） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of JAK1， STAT6， phosphorylated JAK1 （p-JAK1）， and phosphorylated STAT6 （p-STAT6） in the right lung tissue were determined by immunohistochemistry and Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to analyze the transcription levels of JAK1， STAT6 mRNA. ResultsCompared with the blank control group， the model group showed typical pathological features （alveolar structure destruction， interstitial hyperemia， and lymphocyte infiltration） of RILI. Compared with the model group， the DBPT groups （especially the high- and medium-dose groups） exhibited significantly alleviated lung tissue damage. Compared with the blank control group， the model group exhibited elevated serum levels of TNF-α， IL-8， IL-6， and TGF-β （P<0.01）， which were reduced by DBPT in a dose-dependent manner （P<0.05， P<0.01）. Compared with the blank control group， the model group showed decreased p-JAK1/JAK1 and p-STAT6/STAT6 ratios in the lung tissue （P<0.01）. Compared with the model group， DBPT intervention （especially the high dose） increased the p-JAK1/JAK1 and p-STAT6/STAT6 ratios （P<0.05， P<0.01）. Compared with the high-dose DBPT group， high-dose DBPT + AG490 reversed the protective effect of DBPT， leading to aggravated lung injury and increased pro-inflammatory cytokine levels （P<0.05）， confirming the critical role of this pathway. ConclusionDBPT exerts a significant protective effect against RILI. It may activate the JAK1/STAT6 signaling pathway to reduce the release of pro-inflammatory cytokines， thus alleviating RILI. This study suggests that the JAK1/STAT6 pathway is a potential therapeutic target for DBPT in the prevention and treatment of RILI.

AIM:To observe the effects of Huazhuo granules on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/glycogen synthase kinase-3β(GSK-3β)and PI3K/Akt/forkhead box protein O1(FOXO1)signaling pathways in the liver tissue of type 2 diabetes mellitus(T2DM)rats,and to explore its mechanism of action in regulating glycogen synthesis and gluconeogenesis.METHODS:Thirty 8-week-old SPF-grade male SD rats were chosen,with 5 ran-domly selected ones as the blank control group.The remaining 25 rats were fed to a high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin to establish a T2DM rat model.After successful mod-eling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with met-formin,and low,medium,and high-dose Huazhuo granule groups,resulting in a total of 6 groups with 5 rats in each.Rats in the treatment groups were gavaged with the corresponding doses of medication,while those in the blank control and model groups were gavaged with an equal volume of saline once daily for 4 consecutive weeks.After 24-hour fasting with free access to water,the rats were euthanized to measure blood glucose,serum insulin levels,and serum triglyceride(TG),total cholesterol(T-CHO),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels.Liver pathological morphology was assessed by hematoxylin-eosin staining,and liver glycogen storage was detected by periodic acid-Schiff staining.Immunohistochemistry and Western blot analysis were employed to detect the protein levels of p-PI3K,p-Akt,p-FOXO1 and p-GSK-3β in the liver of rats in each group.The mRNA levels of phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6Pase),GSK-3β,FOXO1,PI3K and Akt in liver tissues were detected by RT-qPCR.RESULTS:Compared with the model group,the rats in the high-dose Huazhuo Granule group and the metformin group exhibited decreased blood glucose and insulin levels(P<0.01),reduced AST,ALT,TG,and T-CHO concentrations(P<0.01),and increased HDL-C concentrations(P<0.01).The phosphorylation levels of PI3K,Akt,FOXO1,and GSK-3β proteins were up-regulated(P<0.01).In con-trast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3β were all down-regulated(P<0.01).Conversely,the gene expressions of PI3K and Akt were upregulated(P<0.01).Pathological morphology of the liver tissue improved,accompanied by increased glycogen deposition in hepatocytes.CONCLUSION:Huazhuo granule manifests effects in lowering blood glucose and serum insulin levels,ameliorating blood lipids,and enhancing liver function in rats.These ef-fects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3β signaling pathway and reduce gluco-neogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.

AIM:To observe the effects of Huazhuo granules on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/glycogen synthase kinase-3β(GSK-3β)and PI3K/Akt/forkhead box protein O1(FOXO1)signaling pathways in the liver tissue of type 2 diabetes mellitus(T2DM)rats,and to explore its mechanism of action in regulating glycogen synthesis and gluconeogenesis.METHODS:Thirty 8-week-old SPF-grade male SD rats were chosen,with 5 ran-domly selected ones as the blank control group.The remaining 25 rats were fed to a high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin to establish a T2DM rat model.After successful mod-eling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with met-formin,and low,medium,and high-dose Huazhuo granule groups,resulting in a total of 6 groups with 5 rats in each.Rats in the treatment groups were gavaged with the corresponding doses of medication,while those in the blank control and model groups were gavaged with an equal volume of saline once daily for 4 consecutive weeks.After 24-hour fasting with free access to water,the rats were euthanized to measure blood glucose,serum insulin levels,and serum triglyceride(TG),total cholesterol(T-CHO),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels.Liver pathological morphology was assessed by hematoxylin-eosin staining,and liver glycogen storage was detected by periodic acid-Schiff staining.Immunohistochemistry and Western blot analysis were employed to detect the protein levels of p-PI3K,p-Akt,p-FOXO1 and p-GSK-3β in the liver of rats in each group.The mRNA levels of phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6Pase),GSK-3β,FOXO1,PI3K and Akt in liver tissues were detected by RT-qPCR.RESULTS:Compared with the model group,the rats in the high-dose Huazhuo Granule group and the metformin group exhibited decreased blood glucose and insulin levels(P<0.01),reduced AST,ALT,TG,and T-CHO concentrations(P<0.01),and increased HDL-C concentrations(P<0.01).The phosphorylation levels of PI3K,Akt,FOXO1,and GSK-3β proteins were up-regulated(P<0.01).In con-trast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3β were all down-regulated(P<0.01).Conversely,the gene expressions of PI3K and Akt were upregulated(P<0.01).Pathological morphology of the liver tissue improved,accompanied by increased glycogen deposition in hepatocytes.CONCLUSION:Huazhuo granule manifests effects in lowering blood glucose and serum insulin levels,ameliorating blood lipids,and enhancing liver function in rats.These ef-fects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3β signaling pathway and reduce gluco-neogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.

Objective To observe the effects of modified Liujunzi Decoction on improving isletβ-cell function of patients with the syndrome of spleen-deficiency and phlegm-stagnation of type2 diabetes mellitus.Methods Totally 72 patients were selected and divided into treatment group and control group randomly, with 36 cases in each group. Both groups were under diet adjustment and appropriate exercise and were given metformin hydrochloricle tablets, 0.5 g each time (1.0 g each time after 2 weeks), twice a day; acarbose, 50 mg each time, three times a day. The treatment group was given modified Liujunzi Decoction additionally, 200 mL each time, three times a day, orally. The course of treatment of the two groups was three months. Blood glucose, C peptide, INS, HbA1c, HOMA-IR, HOMA-β andΔI30/ΔG30 after 30 minutes of glucagon loading was recorded.Results Compared with before treatment, FBG, 30 min PBG, 2h PBG, HbA1c, FINS, fasting C-peptide, and HOMA-IR decreased in both groups, and the 30 min INS, 30 min C peptide, andΔI30/ΔG30 increased in the treatment group, with statistical significance (P<0.05). After treatment, there was statistical significance in FBG, 30 min PBG, 2 h PBG, HbA1c, fasting C-peptide, FINS, 30 min INS, 30 min C peptide, HOMA-IR, andΔI30/ΔG30 between the two groups (P<0.05).Conclusion Modified Liujunzi Decoction combined with Western medicine can better improve isletβ-cell function of patients with the syndrome of spleen-deficiency and phlegm-stagnation of type2 diabetes mellitus than Western medicine merely.

Objective To observe the effects of Huazhuo Granule on expression of phosphatidylinositol-3-kinase (PI-3K) and glucose transporter 4 (GLUT4) in skeletal muscle type 2 diabetes (T2DM) rats;To discuss its effects on activating signal path of PI-3K and GLUT4. Methods High-fat diet combined with low-dose streptozotocin intraperitoneal injection was used to establish T2DM rat models. The rats were randomly divided into blank group, Huazhuo Granule group, rosiglitazone group, and model group. Each treatment group was given relevant medicine for gavage. Model group and blank control group were given normal saline for gavage. The general state, weight, and food ration of rats were observed. After ten-week medicine intervention, 10%chloral hydrate was used for anesthesia to detect the levels of FBG, OGTT (2 h PG), and FINS. RT-PCR was used to detect the expressions of PI-3K and GLUT4 mRNA of rat skeletal muscle in all groups. Results Compared with model group, the levels of FBG, 2 h PG, and FINS decreased (P<0.05);the expressions of PI-3K and GLUT4 mRNA of rat skeletal muscle increased significantly (P<0.05). Conclusion Huazhuo Granule has the effects on increasing insulin sensitivity, which is related to activating insulin signal path of PI-3K and GLUT4 of skeletal muscle tissues.