ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

Objective To explore the impact of Shexiang Baoxin Pill(SXBXP,a traditional Chinese patent medicine,broadly applied for the treatment of cardiovascular diseases)on coronary microvascular disease(CMD)and investigate the role and underlying mechanisms of muscone,a key bioactive component of the pills,in the treatment.Methods A total of 16 ob/ob mice(8 weeks old)were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group,receiving 10 mg/kg·d SXBXP or PBS via oral gavage,and another 8 wild-type mice with the same genetic background(WT group)were subjected as a negative control group.Cell model of CMD was established based on mouse coronary microvascular endothelial cells(MCMEC)under ischemia and hypoxic(HI)condition,and the cells were further treated with 20 μg/mL SXBXP(HI+SX)and 30 μmol/L muscone(HI+Muscone),respectively.Echocardiography was carried out for coronary flow reserve(CFR)and left ventricular function,and laser speckle imaging was applied to evaluate myocardial blood flow(MBF).Microvascular density in the heart was evaluated with CD31 immunofluorescence staining.The expression levels of vascular endothelial growth factor(VEGF)in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis.The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.Results In the ob/ob-Control group of mice,the levels of CFR,MBF,and cardiac microvascular density were significantly lower than those in the WT group(P<0.05),and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group(P<0.05),which indicates that SXBXP improves the CMD phenotype.The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice(P<0.05),while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group(P<0.05),illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis.In vitro experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition(P<0.05).Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC(P<0.05).These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.Conclusion SXBXP can improve CMD.Muscone,as a key component of SXBXP,promotes microvascular angiogenesis by inducing the expression of VEGF,then enhances myocardial perfusion,and consequently alleviates CMD.

Objective:To explore the perioperative safety and postoperative short-and long-term efficacy of stomach-partitioning gastrojejunostomy (SPGJ) with distal selective vagotomy (DSV) for treating benign gastric outlet obstruction (GOO).Methods:The clinical data of 26 benign GOO patients treated by Beijing Friendship Hospital, Capital Medical University from January 2019 to July 2023 were retrospectively analyzed. There were 20 males (76.9%) and 6 females (23.1%), aged from 25 to 75 years, with an average age of (55.8±13.6) years, and an average body mass index (BMI) of (20.1±3.4) kg/m 2. There were 12 cases in SPGJ-DSV group and 14 cases in SPGJ group. The main outcome was the gastrointestinal quality of life index (GIQLI) 1 year after surgery in both groups. Independent sample t-test was used to test the difference between the continuous variables with normal distribution. The comparison between groups of non-normal distribution continuous variables was tested by Mann-Whitney U test. Counting data were compared using Chi-square test or Fisher exact test. Results:There were no significant differences between the two groups in terms of operative time ( P=0.071), intraoperative blood loss ( P=0.422), time to pass gas ( P=0.538), time to liquid intake ( P=0.386), postoperative hospitalization ( P=0.431), complications within 30 days after surgery ( P=0.999), and postoperative GOOSS grade ( P=0.483). Among them, postoperative DGE occurred in one patient in each of the two groups, both of which were grade A. In the follow-up results, compared with the SPGJ group, SPGJ-DSV group had a significant advantage in GIQLI score, and the difference was statistically significant ( P=0.028). The incidence of gastric ulcer, reflux esophagitis, bile reflux and gastritis in SPGJ-DSV group was 8.3%, 8.3%, 8.3% and 58.3%, while that in SPGJ group was 35.7%, 21.4%, 21.4% and 57.1%, respectively, but there was no statistical significance between groups. Conclusion:In the treatment of benign GOO patients, SPGJ with DSV did not significantly increase the difficulty of laparoscopic procedures, operative time and intraoperative blood loss. Moreover, it showed a significant advantage in gastrointestinal quality of life 1 year after surgery. In addition, the incidence rates of gastric ulcers and reflux esophagitis were lower in the SPGJ-DSV group 1 year after surgery, but further confirmation is needed in large sample studies.

Background::Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.Methods::The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro. A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry. Results::Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro. AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 +/CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion. Conclusions::This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

ObjectiveTo investigate the influence of different diagnostic criteria on the short-term prognosis of patients with acute-on-chronic liver failure （ACLF）. MethodsA total of 115 ACLF patients who were hospitalized in Department of Gastroenterology， The Second Affiliated Hospital of Kunming Medical University， from January 2018 to January 2022 were enrolled， and all patients received internal medical treatment combined with artificial liver therapy. According to the guidelines， the patients were divided into CMA guideline group （Diagnostic and treatment guidelines for liver failure by Chinese Medical Association）（n=100）， APASL guideline group （Consensus statements of Asian Pacific Association for the Study of the Liver）（n=94）， and EASL guideline group （Criteria proposed by European Association for the Study of the Liver）（n=36）. The above three guidelines were compared in terms of 90-day mortality rate. A one-way analysis of variance was used for comprision of continuous date between groups； the chi-square test was used for comprision of categorical date between groups. The receiver operating characteristic （ROC） curve of related variables. ResultsThe 90-day mortality rate was 50.0% in the CMA guideline group， 51.1% in the APASL guideline group， and 77.8% in the EASL guideline group， and the EASL guideline group had a significantly higher 90-day mortality rate than the CMA guideline group （χ²=8.351， P=0.004） and the APASL guideline group （χ²=7.650， P=0.006）. EASL guideline had a sensitivity of 22.2% and a specificity of 92.3% in predicting the risk of short-term mortality， with an area under the ROC curve was 0.576. ConclusionACLF patients who meet EASL guideline tend to have a worse short-term prognosis， and this guideline may help to identify patients at a relatively high risk of short-term death.

Objective To observe the curative effect of continuous gastrointestinal decompression after gastric lavage with edible oil on saving patients with oral aluminum phosphide poisoning.Methods Seventy-eight patients with oral aluminum phosphide admitted to the Department of Internal Emergency of the Second People's Hospital of Yunnan Province from October 2009 to October 2016 were divided into a mild poisoning group (39 cases), a moderate poisoning group (26 cases) and a severe poisoning group (13 cases) according to clinical manifestations and laboratory examinations, all the patients were treated with continuous gastrointestinal decompression after early gastric lavage with edible oil, including scavenging toxicant, correcting intracellular oxygen intake and metabolic disturbance, and inhibiting and eliminating inflammatory mediators. The difference of remission times of clinical symptoms, recovery times of abnormal indexes and hospitalization times were compared among patients with different disease severities. Results With the aggravation of disease, the remission times of clinical symptoms (hours: from mild to severe were 24±12, 54±18, 84±12), recovery times of abnormal indexes (hours: from mild to severe were 18±6, 72±0, 108±12) and hospitalization times (hours: from mild to severe 48±24, 120±24, 144±24) were all gradually extended. Of the 13 patients with severe poisoning, 2 patients died of multiple organ functional failure (MOF) after 28 hours of treatment because they were incapable of cooperating with continuous gastrointestinal decompression. There were 76 patients were clinically cured, the cure rate being 97.4%. In the follow-ups at 1 month and 6 months after the treatment, no abnormalities were seen.Conclusion Continuous gastrointestinal decompression after early gastric lavage with edible oil for saving patients with oral aluminum phosphide poisoning is an effective therapy worthwhile to be popularized.