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 evaluate the combination score of albumin-bilirubin index(ALBI)and alkaline phosphatase(ALP)in predicting the prognosis of patients with cirrhosis complicated by portal hypertension after receiving transjugular intrahepatic portosystemic shunt(TIPS).Methods A total of 61 patients with cirrhosis complicated by portal hypertension,who received TIPS treatment at the Lishui Municipal Central Hospital of China from January 2016 to June 2024,were retrospectively collected.According to the Youden index of ALBI and ALP,the optimal cut-off values were calculated,and the patients were divided into low ALBI-low ALP group(0-point group),high ALBI-high ALP group(2-point group),and high ALBI-low ALP or low ALBI-high ALP group(one-point group).The efficacy of ALBI-ALP score in predicting the prognosis of patients was evaluated,and the survival rate and median survival time were compared between each other among the three groups.The independent risk factors affecting the survival time of patients were analyzed.Results The maximum Youden indexes of ALBI and ALP were 0.31 and 0.34 respectively,and the optimal cut-off values were-1.56 and 108.50 respectively.There were statistically significant differences in MELD score,Child-Pugh classification,and alanine aminotransferase level between each other among the three groups(all P＜0.05).The area under the ROC curve(AUC)of ALBI-ALP score was 0.77(95％ CI:0.66-0.89,P=0.000 2),which was better than 0.52 of the MELD score(95％ CI:0.37-0.67,P=0.77)as well as better than 0.57 of the Child-Pugh classification(95％ CI:0.43-0.72,P=0.34).The total mortality of patients was 49.18％.The mortality in the 0-point group was 11.11％(2/18),which was significantly lower than 59.46％(22/37)in the one-point group as well as than 100％(6/6)in the 2-point group,and the differences were statistically significant(x2=18.20,P＜0.001).In the 0-point group,as a large number of patients were still alive at the end of the study,the median survival time was unable to be calculated.The median survival time in the one-point group was 38.00 months(95％ CI:23.01-52.99 months),which in the 2-point group was only 1.00 month(95％ CI=0.00-2.60 months),the difference was statistically significant(x2=33.08,P＜0.000 1).In the 0-point group,one-point group and 2-point group,the one-year survival rates were 100％,66％ and 17％respectively,the 2-year survival rates were 100％,64％ and 17％ respectively,and the 3-year survival rates were 90％,53％ and 0％ respectively.Cox multivariate regression analysis showed that the combination score of ALBI and ALP(HR=7.11,95％ CI:2.95-17.15)was an independent risk factor for the survival time of patients with cirrhosis complicated by portal hypertension after receiving TIPS.Conclusion The combination score of ALBI and ALP can effectively predict the prognosis of patients with cirrhosis complicated by portal hypertension after receiving TIPS,and this score is an independent risk factor affecting the survival time of patients.

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.

Purpose To quantitatively evaluate the severity of brain damage in the acute phase of CO poisoning using intravoxel incoherent motion imaging.Materials and Methods MRI scans were performed in 26 patients with CO intoxication of acute stage and 18 healthy controls with matched age and gender.The difference of D value,D* value and f value in different ROIs between the poisoning and the control groups were compared,and the best cut-off values were determined.The correlation between the consciousness state and the D value as well as f value in the vulnerable area of the brain (globus pallidus) was analyzed.Results Compared with control group,the D and F value of the poisoning group were decreased in multiple ROIs,of which statistical significance was observed in the f values in the centrum semiovale,globus pallidus and thalamus,and the D values in the centrum semiovale,lateral ventricle,globus pallidus and corpus callosum splenium (P＜0.05).The best cut-off value,sensitivity and specificity were as follows:fcs=51％,77％,73％;fga=61％,77％,83％;ft=80％,85％,64％;D,=0.69×10-3 mm2/s,85％,83％;Dlv=0.65× 10-3 mm2/s,73％,89％;Dga=0.68× 10-3 mm2/s,62％,83％;Dccs=0.70× 10-3mm2/s,81％,89％.The disturbance of consciousness was positively correlated with decrease of D value and f value (rD=0.828,rf=0.745,P＜0.05).Conclusion The D and f values of intravoxel incoherent motion imaging can quantitatively evaluate the brain damage severity in acute CO poisoning.

Objective To discuss the protective effects ofGuiqi YiyuanOintment on damages caused by heavy ion radiation induced bystander effects; To explore the possible mechanism.Methods Totally 42 Wistar male rats were randomly divided into blank control group, pure radiation group andGuiqi Yiyuan Ointment group. TheGuiqi Yiyuan Ointment group was givenGuiqi Yiyuan Ointment by gavage for two weeks in advance. Later the right lungs of the rats in the pure radiation group andGuiqi Yiyuan Ointment group were radiated once by 2 Gy12C6+, while the blank control group received no radiation. 6, 12, 24 h after radiation all groups of rats were executed. Peripheral hemogram and the levels of IL-6, TGF-β1 and IL-1β in serum of the rats were examined. The changes of lung tissue pathology morphology in the rats were observed by HE staining.Results Compared with the blank control group, the contents of IL-6, TGF-β1 and IL-1β in serum of the pure radiation group increased obviously at 12 h after radiation (P<0.01), and the amount of leukocyte, erythrocyte, blood platelet and hemoglobin distinctly declined at 12 h after radiation (P<0.01); HE staining showed that the alveolar wall was thickened at 24 h after radiation, and there were exudate and inflammatory cell infiltration in the alveolar cavity. Compare with the pure radiation group at 12 h after radiation, the levels of IL-6, TGF-β1 and IL-1β inGuiqi Yiyuan Ointment group decreased significantly at 12 h after radiation (P<0.01). Indexes of blood routine significantly increased (P<0.01), and the pathological changes of lung tissue in rats improved (P<0.01). ConclusionGuiqi Yiyuan Ointment can protect damages caused by heavy ion radiation induced bystander effects.