1.Tongnao Decoction Promotes Angiogenesis and Alleviates Cerebral Ischemic Injury via PI3K/Akt/GSK-3β Signaling Pathway
Yan LIU ; Yang WU ; Wanhui PENG ; Jingyi CHEN ; Jiale GAN ; Li LI ; Yangjingyi XIA ; Yunze LI ; Zhaoyao CHEN ; Wenlei LI ; Minghua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):100-110
ObjectiveTo investigate the mechanisms of Tongnao decoction (TND) in mice with acute ischemic stroke (AIS). MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group, model group, TND low-dose group (1.86 g·kg-1), TND high-dose group (3.72 g·kg-1), and butylphthalide (NBP) group (10 mg·kg-1), with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis (PT). The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T2-weighted imaging (T2WI) was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin (HE) staining was used to observe histological changes in the cerebral cortex, and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging (LSCI) system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine (BrdU) and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), and their phosphorylation levels, as well as tight junction-related proteins zonula occludens-1 (ZO-1), Occludin, and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group, model group, TND low and high dose groups (0.16, 0.32 g·L-1) and NBP group (10 μmol·L-1), with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that, compared with the model group, the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time (P<0.05). HE staining and Nissl staining showed that, compared with the model group, the drug-treated groups exhibited reduced brain tissue damage, fewer scars, and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group (P<0.01), promoting angiogenesis. Meanwhile, compared with the model group, the drug-treated groups upregulated the expression levels of p-PI3K, p-Akt, p-GSK-3β, and tight junction proteins ZO-1, Occludin, and Claudin-5 (P<0.05,P<0.01), and increased the number of intersegmental vessels in zebrafish (P<0.05,P<0.01). ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway, thereby improving cerebral ischemic injury.
2.Robot-assisted radical cystectomy with total intracorporeal ileal conduit: comparative analysis with extracorporeal ileal conduit
Jiale TIAN ; Tianwei YUN ; Wei ZHANG ; Yongming DENG ; Tingsheng LIN ; Yifan SUN ; Rong YANG ; Shiwei ZHANG ; Weidong GAN ; Xiaogong LI ; Gutian ZHANG ; Hongqian GUO
Chinese Journal of Urology 2021;42(7):524-529
Objective:To compare the perioperative complications and prognosis of intracorporeal and extracorporea lileal conduit urinary diversion(ICUD or ECUD)following robot-assisted radical cystectomy(RARC).Methods:The data of 95 patients who underwent RARC treatment in Nanjing Drum Tower Hospital from March 2016 to June 2019 were retrospectively analyzed. Among them, 37 underwent ICUD and 58 underwent ECUD. In the ICUD group, there were 32 males and 5 females, aged(68.0±7.8) years, body mass index (BMI) of (24.1±3.4) kg/m 2, American Society of Anesthesiologists(ASA)score of 1-2 in 4 cases(10.8%), ASA score of 3-5 in 33 cases(89.2%), preoperative hemoglobin of(126.5±14.2)g/L, albumin of(39.0±2.2)g/L, and C-reactive protein of 4.0(2.0-8.5) mg/L. In the ECUD group, there were 53 males and 5 females, aged(67.5±9.0)years, BMI of(24.2±3.6)kg/m 2, ASA score of 1-2 in 16 cases(27.6%), ASA score of 3-5 in 42 cases (72.4%) , preoperative hemoglobin of(129.0±12.4)g/L, albumin (38.2±3.1) g/L, and C-reactive protein of 4.9 (3.1-14.4) mg/L. There was no significant difference in preoperative data between the two groups ( P>0.05). The two groups underwent RARC and pelvic lymph node dissection similarly. The ICUD group underwent a total intracorporeal ileal conduit and the ECUD group underwent extracorporeal ileal conduit with direct vision through a median incision in the lower abdomen.There were 32 cases (86.5%) and 46 cases (79.3%) undergoing expanded pelvic lymph node dissection in the ICUD group and the ECUD group respectively, and the difference was not statistically significant ( P=0.374). The complications were graded according to the Clavien-Dindo grading system. The perioperative complications and prognosis of the two groups were compared. Results:The operation time of the ICUD group and the ECUD group were (430±63) min vs. (410±69) min, respectively ( P=0.163). The estimated blood loss were (435±233) ml vs. (388±277) ml, respectively ( P=0.182). Intraoperative blood transfusion were 10 cases (27.0%) and 12 cases (20.7%)( P=0.475). None of the above differences were statistically significant. Postoperative albumin of the ICUD group and the ECUD group were (31.5±2.4) g/L vs. (31.0±2.8) g/L ( P=0.387), postoperative C-reactive protein were 30.9 (10.4-52.1) mg/L vs.29.5 (14.4-58.5) mg/L ( P=0.655) and postoperative hemoglobin were (110.0±13.8) g/L vs. (113.7±13.4) g/L ( P=0.187). The postoperative feeding recovery were 4(3-5) d vs. 4(3-5) d ( P=0.752) and the postoperative hospital stay were 13(10-19) d vs. 13(11-18) d ( P=1.000). There was no statistically significant difference in perioperative data. The postoperative pathological examination results of ICUD group and ECUD group showed that there were 17 cases (45.9%) vs.19 cases (32.8%) in T a/T 1/Tis stage, 12 cases (32.4%) vs. 18 cases (31.0%) in T 2 stage, 5 cases (13.5%) vs. 19 cases (32.8%) in T 3 stage, 3 cases (8.1%) vs. 2 cases (3.4%) in T 4 stage, respectively and the difference was not statistically significant( P=0.166). The number of lymph nodes removed were (18.2±6.7) vs.(16.5±7.9)( P=0.178) and the number of patients with positive lymph nodes were 6(16.2%) vs.11(19.0%), respectively( P=0.733). None of the patients had positive margins. There was no statistically significant difference in pathological examination overall. There were 14 cases (37.8%) in the ICUD group and 21 cases (36.2%) in the ECUD group experiencing complications within 30 days after operation and the difference was not statistically significant( P=0.872). The complications within 90 days after operation were 14 cases (37.8%) vs. 24 cases (41.4%) respectively and the difference was not statistically significant( P=0.731). Clavien-Dindo grade Ⅲ-Ⅴ complications in the two groups were 1 case (2.7%) vs.1 case (1.7%) respectively, with no significant difference ( P=0.849). One patient in the ICUD group developed an intestinal anastomotic leakage and underwent reoperation for repairing and 1 patient in the ECUD group developed mechanical intestinal obstruction and underwent reoperation. The rate of readmission within 90 days after operation of the ICUD group was lower than that of the ECUD group, but the difference was not statistically significant [3 cases (8.1%) vs. 11 cases (19.0%), P=0.090]. Postoperative follow-up was 13-53 months and the median follow-up of ICUD group and ECUD group were 19 months and 31 months respectively. There was no significant difference in the survival curve between the two groups( P=0.746). The 1-year survival rate was 91.9% in the ICUD group and 91.4% in the ECUD group. Routine re-examination of urinary system CT or B-ultrasound was performed 3 months, 6 months and 1 year after surgery. The incidence of ureteral dilatation/hydronephrosis in the ICUD group was lower than that of the ECUD group, with 4.1%(3 sides) vs. 14.7%(17 sides)( P=0.020). Conclusion:Compared with RARC+ ECUD, RARC+ ICUD does not increase the incidence of complications within 90 days after surgery and may reduce the risk of upper urinary tract dilatation.
3.Influence of Zhali Nusi Recipe on Hemorheology and Metabolism of Blood Lipid and Free Radicals of Cerebral Ischemia-Reperfusion Rats with Syndrome of Phlegm Blended with Blood Stasis
Shuwen LIU ; Jingxia LIU ; Chao LIU ; Jiale GAN ; Xicheng HU ; Feifei REN
Journal of Guangzhou University of Traditional Chinese Medicine 2015;(5):884-890,895
Objective To investigate the effect of Zhali Nusi Recipe ( ZNR) on hemorheological parameters, blood - lipid metabolism, the activities of superoxide dismutase ( SOD) and glutathione peroxidase ( GSH-Px) , and the content of malondialdehyde (MDA) in brain tissues of cerebral ischemia-reperfusion rats with the syndrome of phlegm blended with blood stasis. Methods Ninety rats were randomly divided into sham operation group, model group, nimodiping (10.8 mg/kg) group, high-, middle- and low-dose ZNR groups ( in the dosage of 30, 15, 7.5 g/kg, respectively) , 15 rats in each group. Except the sham operation group, the other groups were given intragastric administration of intralipid for 4 weeks, and then were induced into focal cerebral ischemia-reperfusion by middle cerebral artery occlusion with thread-obstruction method. After post-operation medication for 7 days, the rat general situations, the neurological deficiency symptoms, and the water content in brain tissues were observed. The morphological features of brain tissues were observed after HE staining. The blood was taken from the ab dominal aorta to detect the hemorheological parameters and blood lipid levels. Metabolic levels of free radicals in the brain tissue homogenate were also determined. Results Compared with the sham operation group, neurological deficiency scores of the rats and the water content in the brain tissues of model group were significantly enhanced. The hippocampal neurons of model rats presented typical ischemic changes. In the model group, the hemorheological parameters such as whole blood viscosity, plasma viscosity, hematocrit ( HCT) , and erythrocyte aggregation in dexes ( EAI) were significantly increased, and erythrocyte deformation indexes were significantly decreased; the serum levels of total cholesterol ( TC) , triglyceride ( TG) , low-density lipoprotein cholesterol (LDL-C) were significantly increased, and high-density lipoprotein cholesterol ( HDL-C) level was significantly decreased; the activities of SOD and GSH-Px in brain tissues were significantly decreased, and MDA content was increased significantly ( P<0.05 or P<0.01). Compared with the model group, high-, middle-and low-dose ZNR improved the general situations of the cerebral ischemia-reperfusion rats, increased the neurological deficiency scores, reduced the water content in brain tissues, improved the recovery of morphology of cells in cerebral ischemia tissues, reduced whole blood viscosity, plasma viscosity, HCT and EAI of the model rats, promoted erythrocyte deformation indexes, decreased serum TG, TC, LDL-C levels, increased the activities of SOD and GSH-Px in cerebral ischemic tissues, and sig nificantly decreased MDA content (P<0.05 or P<0.01). And high-dose ZNR had the best effect. Conclusion ZNR has certain protective effect on cerebral ischemia-reperfusion rats with the syndrome of phlegm blended with blood stasis, and the mechanism may be closely related with the improvement ofhemorheology, blood lipid and free radical metabolism in model rats.

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