Objective To investigate the protective effect of Linggui Zhugan Decoction on myocardial injury in diabetic rats;To explore its molecular mechanism.Methods The diabetes myocardial injury rat model was established by intraperitoneal high fat diet combined with injection of streptozotocin.Successfully modeled rats were randomly divided into model group,simvastatin group(5 mg/kg)and Linggui Zhugan Decoction low-and high-dosage group(3.75,7.5 g/kg).Normal rats were set as blank group,and each medication group was intervened with corresponding drugs.Fasting and random blood glucose were monitored using a glucometer,the left ventricular ejection fraction(LVEF)was measured,serum contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by biochemical kits,the contents of cardiac troponin I(cTnI)and creatine kinase-MB(CK-MB)were detected by ELISA,the myocardial morphology and fibrosis were observed by HE and Masson staining,the positive expression of PDCD4 was detected by immunohistochemistry,the mRNA expressions of miR-21,PDCD4,PTEN and p53 were detected by RT-qPCR,and the protein expressions of PDCD4,PTEN and p53 were detected by Western blot.Results Compared with the blank group,fasting blood glucose and random blood glucose significantly increased at different time points in the model group(P<0.05,P<0.01),LVEF significantly decreased(P<0.01),the contents of serum TC,TG,LDL-C,HDL-C,MDA,cTnI,CK-MB significantly increased(P<0.05,P<0.01),and the content of SOD significantly decreased(P<0.01);the inflammatory cells infiltration and fibrosis injury in myocardial tissue were significantly aggravated(P<0.01),the expression of miR-21 in myocardial tissue significantly decreased,and the mRNA and protein expressions of PDCD4,PTEN,p53 significantly increased(P<0.05,P<0.01).Compared with the model group,fasting blood glucose significantly decreased in simvastatin group and Linggui Zhugan Decoction high-dosage group(P<0.05),LVEF significantly increased(P<0.01),the contents of serum TC,TG,LDL-C,HDL-C,MDA,cTnI and CK-MB significantly decreased(P<0.05,P<0.01),the content of SOD significantly increased(P<0.05,P<0.01);the inflammatory cells infiltration and fibrosis injury in myocardial tissue were significantly improved(P<0.01),the expression of miR-21 in myocardial tissue significantly increased,and the mRNA and protein expressions of PDCD4,PTEN,p53 significantly decreased(P<0.05,P<0.01).Conclusion Linggui Zhugan Decoction may inhibit the expressions of PDCD4,PTEN and p53 by increasing miR-21,thereby alleviating myocardial injury in diabetic rats.

Objective:To investigate the application value of optimized mesenteric defect closure technique in laparoscopic-assisted right hemicolectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 26 patients who underwent laparo-scopic-assisted right hemicolectomy at Changzhi People′s Hospital Affiliated to Changzhi Medical College from May 2023 to June 2024 were collected. There were 11 males and 15 females, aged (65.7±1.8)years. All patients received optimized mesenteric defect closure using a combined extra-corporeal-laparoscopic suturing technique. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical and intraoperative conditions. All 26 patients underwent laparoscopic-assisted right hemicolectomy with optimized mesenteric defect closure. The time of optimized mesenteric defect closure was 9.8(8.8,12.8)minutes, time of digestive tract reconstruction was 10.0(8.7,13.0)minutes, operation time was (164±4)minutes, volume of intraoperative blood loss was 50(50,100)mL. One of the 26 patients had intraoperative mesenteric hematoma, which required no specific intervention. The patient recovered uneventfully and was discharged from hospital. (2) Postoperative conditions. The visual analog scale pain score of 26 patients on postoperative day 1 and day 3 were 5(4,5) and 3(2,3), respectively. Time to postoperative first anal flatus and bowel movement were both 3(3, 4)days. Time to postoperative first intake of liquid diet was 2(2,3)days, duration of postoperative abdominal drainage was 4(3,5)days, and duration of postoperative hospital stay was 9(8,12)days. The number of lymph node dissected in 26 patients was 25(18,27) and the number of positive lymph node was 1(0,2). Cases in stage Ⅰ, stage Ⅱ and stage Ⅲ of tumor TNM staging were 5, 6, 15. (3) Follow-up. All 26 patients were followed up for 15(range, 6?20)months. Of the 26 patients, one case had incom-plete intestinal obstruction on postoperative day 25, which was diagnosed as adhesive intestinal obstruction based on imaging examination and classified as Clavien-Dindo grade Ⅱ. The patient recovered and was discharged after conservative treatment. None of the 26 patients had bleeding, infection of incision, anastomotic leakage, internal hernia, or delayed gastric emptying. There was no tumor recurrence, metastasis or death.Conclusion:The optimized mesenteric defect closure tech-nique in combined extracorporeal-laparoscopic suturing procedure can be used in laparoscopic-assisted right hemicolectomy.

Objective:To investigate the application value of optimized mesenteric defect closure technique in laparoscopic-assisted right hemicolectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 26 patients who underwent laparo-scopic-assisted right hemicolectomy at Changzhi People′s Hospital Affiliated to Changzhi Medical College from May 2023 to June 2024 were collected. There were 11 males and 15 females, aged (65.7±1.8)years. All patients received optimized mesenteric defect closure using a combined extra-corporeal-laparoscopic suturing technique. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical and intraoperative conditions. All 26 patients underwent laparoscopic-assisted right hemicolectomy with optimized mesenteric defect closure. The time of optimized mesenteric defect closure was 9.8(8.8,12.8)minutes, time of digestive tract reconstruction was 10.0(8.7,13.0)minutes, operation time was (164±4)minutes, volume of intraoperative blood loss was 50(50,100)mL. One of the 26 patients had intraoperative mesenteric hematoma, which required no specific intervention. The patient recovered uneventfully and was discharged from hospital. (2) Postoperative conditions. The visual analog scale pain score of 26 patients on postoperative day 1 and day 3 were 5(4,5) and 3(2,3), respectively. Time to postoperative first anal flatus and bowel movement were both 3(3, 4)days. Time to postoperative first intake of liquid diet was 2(2,3)days, duration of postoperative abdominal drainage was 4(3,5)days, and duration of postoperative hospital stay was 9(8,12)days. The number of lymph node dissected in 26 patients was 25(18,27) and the number of positive lymph node was 1(0,2). Cases in stage Ⅰ, stage Ⅱ and stage Ⅲ of tumor TNM staging were 5, 6, 15. (3) Follow-up. All 26 patients were followed up for 15(range, 6?20)months. Of the 26 patients, one case had incom-plete intestinal obstruction on postoperative day 25, which was diagnosed as adhesive intestinal obstruction based on imaging examination and classified as Clavien-Dindo grade Ⅱ. The patient recovered and was discharged after conservative treatment. None of the 26 patients had bleeding, infection of incision, anastomotic leakage, internal hernia, or delayed gastric emptying. There was no tumor recurrence, metastasis or death.Conclusion:The optimized mesenteric defect closure tech-nique in combined extracorporeal-laparoscopic suturing procedure can be used in laparoscopic-assisted right hemicolectomy.

Objective To investigate the protective effect of Linggui Zhugan Decoction on myocardial injury in diabetic rats;To explore its molecular mechanism.Methods The diabetes myocardial injury rat model was established by intraperitoneal high fat diet combined with injection of streptozotocin.Successfully modeled rats were randomly divided into model group,simvastatin group(5 mg/kg)and Linggui Zhugan Decoction low-and high-dosage group(3.75,7.5 g/kg).Normal rats were set as blank group,and each medication group was intervened with corresponding drugs.Fasting and random blood glucose were monitored using a glucometer,the left ventricular ejection fraction(LVEF)was measured,serum contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by biochemical kits,the contents of cardiac troponin I(cTnI)and creatine kinase-MB(CK-MB)were detected by ELISA,the myocardial morphology and fibrosis were observed by HE and Masson staining,the positive expression of PDCD4 was detected by immunohistochemistry,the mRNA expressions of miR-21,PDCD4,PTEN and p53 were detected by RT-qPCR,and the protein expressions of PDCD4,PTEN and p53 were detected by Western blot.Results Compared with the blank group,fasting blood glucose and random blood glucose significantly increased at different time points in the model group(P<0.05,P<0.01),LVEF significantly decreased(P<0.01),the contents of serum TC,TG,LDL-C,HDL-C,MDA,cTnI,CK-MB significantly increased(P<0.05,P<0.01),and the content of SOD significantly decreased(P<0.01);the inflammatory cells infiltration and fibrosis injury in myocardial tissue were significantly aggravated(P<0.01),the expression of miR-21 in myocardial tissue significantly decreased,and the mRNA and protein expressions of PDCD4,PTEN,p53 significantly increased(P<0.05,P<0.01).Compared with the model group,fasting blood glucose significantly decreased in simvastatin group and Linggui Zhugan Decoction high-dosage group(P<0.05),LVEF significantly increased(P<0.01),the contents of serum TC,TG,LDL-C,HDL-C,MDA,cTnI and CK-MB significantly decreased(P<0.05,P<0.01),the content of SOD significantly increased(P<0.05,P<0.01);the inflammatory cells infiltration and fibrosis injury in myocardial tissue were significantly improved(P<0.01),the expression of miR-21 in myocardial tissue significantly increased,and the mRNA and protein expressions of PDCD4,PTEN,p53 significantly decreased(P<0.05,P<0.01).Conclusion Linggui Zhugan Decoction may inhibit the expressions of PDCD4,PTEN and p53 by increasing miR-21,thereby alleviating myocardial injury in diabetic rats.

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K _D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

Objective:To evaluate the effect of down-regulation of Sp1 expression on the radiosensitivity of glioma cells.Methods:The oligonucleotide sequence encoding shRNA was designed and synthesized, and cloned into LV3 (H1/GFP & Puro) vector to construct the recombinant. U251 and U87 cells were infected with recombinant lentivirus, then the stably-transfected cell lines were obtained by puromycin screening. The expression levels of Sp1 mRNA and protein were detected by RT-PCR and Western blot. Cell survival was detected by clonal survival assay, cell cycle was determined by flow cytometry, and DNA damage was measured by immunofluorescence assay, respectively.Results:At 72 h after infection, high expression of Sp1 lentiviral vector was observed in two cell lines under fluorescence microscope. RT-PCR and Western blot confirmed that the expression levels of Sp1 mRNA and protein were significantly down-regulated in both transfected cells (both P<0.01) and the silencing rates of Sp1 were above 90%. The sensitization enhancement ratio (SER) of shRNA-U251 and shRNA-U87 cells at 10% cell survival level were 1.39 and 1.18, respectively. After irradiation, the G 2/M phase ratio and the number of γ-H2AX foci in two Sp1 knockout groups were significantly increased. Conclusion:shRNA silencing of Sp1 increases the G 2/M phase arrest induced by X-ray, aggravates the degree of DNA double-strand breaks, and improves the radiosensitivity of glioma cells.

Objective To investigate the change of the percentage of Th17 cells and cytokine among hepatocellular carcinoma (HCC) tissues and para-carcinoma tissue and the liver tissue of hepatic hemangio-ma, and to explore its clinical significance. Methods To choose 26 of hepatocellular carcinoma patients between November 2014 and December 2016 and also include 11 cases of hepatic hemangioma as control group. The percentage of Th17cells in HCC tissue and para-carcinoma tissue and the liver tissue of hepatic hemangioma was evaluated by flow cytometric; The levels of IL-6 and IL-17 in HCC tissues, para-carcinoma tissue and the liver tissue of hepatic hemangioma were detected by RT-PCR. Results The ratio of Th17 cells to CD4 cells in peripheral blood of HCC was significantly higher than that in control group (4. 07% ± 0. 68% vs. 1. 39% ± 0. 41% ), P＜0. 05. The ratio of Th17 cells to CD4 cells in patients with hepatocellular carcinoma was significantly higher than that in paracancerous tissues and liver tissues of hepatic hemangioma (4. 76% ± 0. 75% vs. 2. 30% ± 0. 26% vs. 0. 77% ± 0. 31% , P＜0. 05). Multivariate linear stepwise regression analysis of the changes of Th17 cells in patients with HCC and their correlation with clinical parameters showed that Th17 lymphocytes in peripheral blood of patients with HCC were closely related to TNM staging(YTh17 =2. 647 +0. 687TNM. It’s indicated that the level of IL-6 and IL-17 in liver cancer tissues was significantly higher than that of the liver hemangioma in the control group through ELISA ( P＜0. 05). The proportion of peripheral blood Th17 cells to CD4 cells is different in different TNM stages(stage I＜stage II ＜stage III ～IV, the difference was statistically significant. RT-PCR analysis showed that the expression of IL-17, IL-6mRNA in hepatocellular carcinoma was significantly higher than that in adjacent tissues and hepatic hemangioma liver tissue (all P＜0. 05). Conclusion The increased proportion of Th17 cells and the increased levels of cytokines IL-6 and IL-17 may be closely correlated with occurrence and development of hepatocellular carcinoma. It can be an important target of anti-tumor therapy.

Objective To explore the anti-inflammatory effect of erythropoietin (EPO) on hepatic ischemia reperfusion (IR) injury in fatty liver rats.Methods A total of 100 male SD rats were fed with high-fat diet for 12 weeks.After the model was successfully established,the fatty liver rats were randomly divided into sham-operation (SHAM),the ischemia-reperfusion (IR) and EPO preconditioning group.Serum ALT and AST as well as hepatic histopathological changes were measured.Xanthine oxidase method was used to detect the liver tissue SOD.Thiobarbituric acid method was used to detect the MDA.Enzyme-linked immunosorbent adsorption assay (ELISA) was used to detect the plasma tumor necrosis factor alpha (TNFαt) and interleukin 1 (IL-1).Results In the EPO preconditioning groups the swelling hepatocytes was observed,but the inflammatory cell infiltration was significantly decreased and no necrosis of hepatocytes was found.ALT and AST in the EPO preconditioning groups were significantly lower than those in IR group (P ＜ 0.05).The levels of SOD activity in the EPO preconditioning groups were significantly higher,but MDA were significantly lower than that in IR group (P ＜ 0.05).The TNF-α and IL-1 in the EPO preconditioning groups were significantly lower than those in IR group (P ＜0.05).The values of ALT,AST,TNF-α,IL-1 and MDA in the EPO groups were:EPO-1 ＞ EPO-2 ＞ EPO-3 (P ＜ 0.05);but the values of SOD in the EPO groups were:EPO-1 ＜ EPO-2 ＜ EPO-3 (P ＜ 0.05).Conclusions EPO preconditioning has a protective effect against hepatic IR injury in fatty liver rats,possibly through inhibiting the inflammatory reaction to prevent the IR injury.The anti-inflammatory effect of high-dose EPO is better than that of low-dose EPO.

Adenoma, Liver Cell ; Gallbladder Diseases ; Histiocytosis, Sinus ; Humans ; Liver Neoplasms