1.Mechanism of Yitangkang Granule in Promoting Podocyte Autophagy Through Regulation of PI3K/Akt/FoxO1 Signaling Pathway Mediated by SIRT1 via AGE-RAGE Axis
Yuefeng CHENG ; Jiaxiang YU ; Hanwen ZHANG ; Chao QU ; Yifei HUO ; Xiaorui ZHANG ; Yan SHI ; Wenshun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):113-121
ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule(YTK) treats diabetic kidney disease (DKD) by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkhead transcription factor O1 (FoxO1) signaling pathway mediated by silent information regulator 1 (SIRT1) via advanced glycation end products (AGE)/receptor for AGE (RAGE) axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group (B), model control group, high-dose YTK (40 g·kg-1), medium-dose YTK (20 g·kg-1), low-dose YTK (10 g·kg-1), and Western medicine control (20 mg·kg-1 losartan) groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling, the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured according to the instructions of the respective assay kits. Hematoxylin and eosin (HE) staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin (α-SMA), fibronectin (FN), desmin, and nephrin. Western blot analysis was used to measure the expression levels of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), RAGE, SIRT1, Caspase-3, and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group, the model group showed significantly lower levels of SOD, GSH-Px, and CAT, and significantly higher levels of MDA (P<0.01). The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA, FN, and desmin increased significantly, while nephrin and podocin significantly decreased (P<0.01). The expression levels of PI3K, p-PI3K, Akt, p-Akt, RAGE, and Caspase-3 proteins were significantly elevated, while SIRT1 and FoxO1 protein levels were significantly reduced (P<0.01). Compared with the model control group, rats in the YTK treatment groups showed significantly higher levels of SOD, GSH-Px, and CAT, and significantly lower levels of MDA in serum (P<0.01). The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA, FN, and desmin were significantly decreased, while nephrin and podocin significantly increased (P<0.01). The expression levels of PI3K, p-PI3K, Akt, p-Akt, RAGE, and Caspase-3 in kidney tissues were significantly reduced, while SIRT1 and FoxO1 expression levels significantly increased (P<0.01). The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage, reduce proteinuria, and protect kidney function in DKD rats, thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally, a dose-response relationship was observed in the Chinese medicine groups.
2.Mechanism of Yitangkang in Improving Apoptosis of Skeletal Muscle Cells by Inhibiting AGE/RAGE Signaling Pathway
Jiaxiang YU ; Hanwen ZHANG ; Lie WANG ; Yan SHI ; Rui YU ; Jianyu DAI ; Chao QU ; Xiande MA ; Xueying HAN ; Zhimin WANG ; Jiren AN ; Yuefeng CHENG ; Hongkai JI ; Wenshun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):54-64
ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance (IR) by inhibiting the advanced glycation end product (AGE)/receptor for the advanced glycation end product (RAGE) signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group, a model group, high-, medium-, and low-dose Yitangkang-medicated serum groups (40, 20, and 10 g·kg-1), and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted,the cell viability and glucose consumption level of each group were determined. In addition,the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), p53, cysteinyl aspartate-specific protease-3 (Caspase-3), and cysteinyl aspartate-specific protease-9 (Caspase-9)] were determined using Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group, a model group, high-,medium-,and low-dose Yitangkang groups (40, 20, and 10 g·kg-1), and a western medicine group (pioglitazone hydrochloride,1.35 mg·kg-1). The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin (STZ) in animals and verified by the hyperinsulinemic-euglycemic clamp (HEC) test. After the model was determined successfully, the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group,while Real-time polymerase chain reaction(Real-time PCR) and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2, Bax, p53, Caspase-3, and Caspase-9. Result① In vitro experiments. compared with the blank group, the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption (P<0.01). Compared with the model group, the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption (P<0.01). Compared with the blank group, the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.01). Compared with the model group, the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells (P<0.01) and decreased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.05, P<0.01). ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group (P<0.01). The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group (P<0.01). Compared with the blank group, the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.01). Compared with the model group, the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats (P<0.01) and decreased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.05, P<0.01). The medium-dose Yitangkang showed a similar effect as RAGE inhibitor, and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.
3. Preparation and pharmacokinetics in vivo of linarin solid dispersion and liposome
Yingying HUANG ; Lihua XU ; Fangping ZHANG ; Yang LIU ; Yunyu WANG ; Fangfeng MENG ; Shuang LI ; Xintao CHENG ; Yuefeng BI ; Yang LIU ; Yuefeng BI
Chinese Herbal Medicines 2022;14(2):310-316
Objective: The current investigation aimed to determine the appropriate dosage form by comparing solid dispersion and liposome to achieve the purpose of improving the solubility and bioavailability of linarin. Methods: Linarin solid dispersion (LSD) and linarin liposome (LL) were developed via the solvent method and the thin film hydration method respectively. The Transwell chamber model of Caco-2 cells was established to evaluate the absorption of drug. The pharmacokinetics of linarin, LSD and LL in rats after ig administration were carried out by high performance liquid chromatography (HPLC) method. Results: The solubility of LSD and LL was severally 3.29 times and 3.09 times than that of linarin. The permeation coefficients of LSD and LL were greater than 10
4.Surgical strategies of atrioventricular septal defect with left ventricular outflow tract stenosis: Clinical outcome of single center
Yuefeng CAO ; Lei LI ; Junwu SU ; Pei CHENG ; Xiangming FAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(09):1072-1075
Objective To explore the anatomical characteristics and surgical strategies of atrioventricular septal defect (AVSD) with left ventricular outflow tract (LVOT) stenosis. Methods The clinical data of 11 AVSD patients with LVOT stenosis who underwent surgeries in our hospital from 2008 to 2019 were retrospectively analyzed, including 6 males and 5 females with a median age of 15.0 (7.6-22.0) years. Results There were 3 patients of complete AVSD and 8 patients of partial AVSD. Subaortic stenosis resulted from discrete subaortic membrane in 3 patients, diffused subaortic membrane in 4 patients, hypertrophied muscle bundles in 3 patients and distorted valve frame in 1 patient. Among these patients, 5 patients underwent LVOT stenosis and AVSD repairs simultaneously for the first time, 5 patients underwent LVOT stenosis repair for the second time and 1 patient for the third time. No postoperative death occurred. The postoperative LVOT flow velocity decreased dramatically after LVOT stenosis repair compared with preoperative one [449.0 (393.0, 507.5) cm/s vs. 212.0 (183.0, 253.5) cm/s, P<0.05]. Conclusion Surgical results of AVSD combined with LVOT stenosis are satisfactory, but the restenosis should be paid attention to via long-term follow-up.
5.The clinical analysis of endoscopic pancreaticobiliary separation in the treatment of occult pancreaticobiliary reflux
Cheng ZHANG ; Yulong YANG ; Hai HU ; Gang ZHAO ; Meiju LIN ; Yuefeng MA ; Chunchun QI
Chinese Journal of General Surgery 2019;34(2):147-150
Objective To evaluate endoscopic pancreaticobiliary separation (EPBS) in patients with gallstone and occult pancreaticobiliary reflux (OPBR).Methods The clinical data of 47 cases with gallstone and OPBR from Oct 2013 to Oct 2016 was analyzed retrospectively.Results The mean gallbladder bile amylase (GBA) was (864 ± 575) U/L.40 cases have undergone the treatment of endoscopic retrograde cholangiopancreatography.26 cases were diagnosed as duodenal papillitis,16 cases as periampullary diverticula,14 cases as long nipple,5 cases as atrophic papilla,3 cases as ampulla stone and 2 cases as papillary tumor.9 were diagnosed as pancreaticobiliary maljunction in the 14 patients with long nipple.33 cases were performed with EPBS.GBA was tested in 16 cases,and the GBA of 15 cases returned to normal level.The difference of GBA was statistically significant [(1 161 ±764) U/L vs.(47 ± 17) U/L,(t =5.641,P < 0.05)].Patients were followed up for 1 to 4 years,among 36 cases without cholecystectomy,there was no recurrence of cholecystolithiasis after EPBS in 27 cases,but 2 cases had recurrent gallstones in 9 cases without EPBS,and the difference of gallstone recurrence rate was statistically significant (x2 =21.340,P < 0.05).Conclusions Pancreaticobiliary junction diseases is an important cause for gallstone formation and OPBR.EPBS can avoid pancreaticobiliary reflux and reduce the recurrence rate of gallstone after choledochoscopic lithotomy.
6.A retrospective comparison of thoracoscopic and laparoscopic esophagectomy between right neck anastomosis and left neck anastomosis.
Yanzhao XU ; Xinqiang SHI ; Jingge CHENG ; Yuefeng ZHANG ; Shiwang WEN ; Zhenhua LI ; Huilai LVY ; Ziqiang TIAN
Chinese Journal of Gastrointestinal Surgery 2018;21(9):1008-1012
OBJECTIVETo evaluate the feasibility of right neck anastomosis in thoracoscopic and laparoscopic esophagectomy.
METHODSThis study used a retrospective cohort study method. Clinical data of 169 patients with stage I-III esophageal squamous cell carcinoma undergoing neck anastomosis in thoracoscopic and laparoscopic esophagectomy at the Department 5 of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from November 2013 to October 2016 were retrospectively analyzed. Eighty-two cases underwent right neck anastomosis (right neck anastomosis group) and 87 cases underwent left neck anastomosis(left neck anastomosis group). Both groups underwent routine thoracoscopic and laparoscopic radical resection of esophageal cancer. The entry of right and left neck anastomosis group was at the anterior edge of the right and left sternocleidomastoid muscle respectively. Anastomosis of the esophagogastric junction was performed and the drainage tube was placed in the neck incision. The operation time, intraoperative blood loss, lymph node dissection and morbidity of postoperative complications were compared between the two groups.
RESULTSThere were 101 males and 68 females among 169 patients with esophageal cancer. There were no significant differences in age, gender, tumor location, clinical stage between two groups(all P>0.05). The total operation time of left and right neck anastomosis groups was (278.3±39.4) minutes and (287.8±39.4) minutes, respectively (t=1.563, P=0.120). The intraoperative blood loss was (134.9±71.5) ml and(147.9±85.5) ml, respectively (t=1.074, P=0.284). The number of lymph node dissections was (17.45±5.68) and (16.47±4.98), respectively (t=1.190, P=0.236). Seventeen cases(20.7%) in the right neck anastomosis group developed postoperative complications, while 31 cases (35.6%) in the left neck anastomosis group developed postoperative complications (χ²=4.609,P=0.032). Compared with left neck anastomosis group, right neck anastomosis group had lower rate of gastric emptying disorder (0% vs. 6.9%, P=0.029), anastomotic fistula (7.3% vs. 18.4%, χ²=4.572, P=0.033), pneumonia (18.3% vs. 32.2%, χ²=4.294, P=0.038) and ICU management (4.9% vs. 16.1%, χ²=4.726, P=0.030).
CONCLUSIONThoracoscopic and laparoscopic esophagectomy with right neck anastomosis is safe and effective, can completely remove the tumor, at the same time, has less complications than left neck anastomosis, and improve the quality of life.
Anastomosis, Surgical ; Esophageal Neoplasms ; surgery ; Esophagectomy ; Female ; Humans ; Laparoscopy ; Lymph Node Excision ; Male ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Thoracoscopy
7.Pancreatic stent in prevention of postoperative acute pancreatitis in patients with benign biliary stricture treated by full-covered self-expanding removable metal stents
Cheng ZHANG ; Hai HU ; Hongwei ZHANG ; Yulong YANG ; Meiju LIN ; Gang ZHAO ; Yuefeng MA
Chinese Journal of General Surgery 2018;33(9):725-728
Objective To investigate the clinical value,safety and efficacy of pancreatic stent in prevention of postoperative acute pancreatitis in patients with benign biliary stricture (BBS) treated by fullcovered self-expanding removable metal stents (FCSERMSs).Methods From Jan 2011 to Dec 2017,92 BBS patients who met the inclusion criteria were admitted and divided into pancreatic stent (PS) group and control group.The acute pancreatitis (AP) and hyperamylase (HP) after FCSERMS implantation and removal was observed.Results 55 cases in PS group and 37 cases in control group underwent successful FCSERMS implantation.The incidences of postoperative elevated amylase and HP had no significant differences between the two groups (23.6% vs.32.4%,3.6% vs.10.8%,all P >0.05).The incidences of postoperative AP and moderately elevated amylase had significant differences (0 vs.13.5%,20.0% vs.8.1%,all P < 0.05).The average placement time of FCSERMSs was 7.84 ± 1.22 months.The incidence of elevated amylase,AP,HP and moderately elevated amylase after the FCSERMS and PS removed had no statistical differences (3.6% vs.14.3%,0vs.2.9%,0 vs.2.9%,3.6%vs.8.6%,all P>0.05).Conclusion The placement of pancreatic stents in the treatment of BBS with FCSERMS is a simple,safe and effective method for the prevention of post-ERCP pancreatitis.
8.Application of X-ray assisted nasal catheter extractor to nose biliary oronasal conversion
Cheng ZHANG ; Yulong YANG ; Jingyi LI ; Meiju LIN ; Yuefeng MA ; Lijun SHI ; Hongwei ZHANG ; Chunchun QI
Chinese Journal of Digestive Endoscopy 2018;35(3):167-170
Objective To investigate the effect of X-ray assisted nasal catheter extractor on nose biliary oronasal conversion. Methods A total of 892 patients,receiving endoscopic nasal biliary drainage in Affiliated Zhongshan Hospital of Dalian University from January 2014 to December 2015, were randomly divided into experiment group and control group. X-ray assisted nasal catheter extractor was used in the experiment group,and guide wire was used in the control group. The mean extracting number and operation time, the total success rate, one-time success rate, response to stimulation and the incidence of complications were compared between the two groups. Results There were 457 cases in the experiment group. The mean extracting number was 1.08±0.32,the mean operation time was 1.07±0.29 min,the total success rate was 100.00%(457/457)and one-time success rate was 93.65%(428/457). The stimulation degree score was 1.27±0.50 with 348 cases of mild response,96 cases of moderate response and 13 cases of severe response. The rate of adverse reaction was 15.54%(71/457)with 50 cases of nausea, 18 cases of vomiting and 3 cases of mucosal bleeding. There were 435 cases in control group. The mean extracting number was 1.68±0.61,the mean operation time was 1.75±0.53 min, the total success rate was 75.63%(329/435)and one-time success rate was 38.16%(166/435). The stimulation degree score was 1.59 ±0.62 with 210 cases of mild response,194 cases of moderate response and 31 cases of severe response. The rate of adverse reaction was 35.86%(156/435)with 87 cases of nausea,36 cases of vomiting,27 cases of mucosal bleeding,and 6 cases of nasal duct prolapsed for vomiting. There were significant differences in the mean extracting number, mean operation time, stimulation degree score and the adverse reaction rate between the two groups(all P<0.001). The total success rate and one-time success rate in the experiment group were higher than those in the control group(all P<0.001).Conclusion X-ray assisted nasal catheter extractor can improve the success rate of operation,shorten the operation time,reduce the stimulation degree and the rate of adverse reactions in nose biliary oronasal conversion.
9.Effect of drinking water test combined with swallowing training for the treatment of cerebral infarction patients with dysphagia
Guoju LIU ; Yun DING ; Yuefeng CHENG ; Caihong LIANG
Journal of Clinical Medicine in Practice 2018;22(2):5-8
Objective To explore the therapeutic effect of drinking water test combined with swallowing training on cerebral infarction patients with dysphagia.Methods A total of 68 cerebral infarction patients with dysphagia in our department were randomly divided into observation group and control group.The control group was given routine nursing,while the observation group was given drinking water test to guide diet,and systemic swallowing function training on the basis of the control group.The therapeutic effects,feeding conditions and VSD scale scores were compared after 1 month of intervention between the two groups.Results The drinking water test score in the observation group was lower than that in the control group,and the total effective rate of the swallowing function improvement was higher than that in the control group,the differences were statistically significant (P < 0.05).The FOIS score in the observation group was higher,and the score of VSD scale was lower than that in the control group,the differences were statistically significant (P < 0.05).Conclusion Drinking water test combined with swallowing training can effectively improve the swallowing function of patients with dysphagia after cerebral infarction,and is beneficial to the normal diet of the patients.
10.Effect of drinking water test combined with swallowing training for the treatment of cerebral infarction patients with dysphagia
Guoju LIU ; Yun DING ; Yuefeng CHENG ; Caihong LIANG
Journal of Clinical Medicine in Practice 2018;22(2):5-8
Objective To explore the therapeutic effect of drinking water test combined with swallowing training on cerebral infarction patients with dysphagia.Methods A total of 68 cerebral infarction patients with dysphagia in our department were randomly divided into observation group and control group.The control group was given routine nursing,while the observation group was given drinking water test to guide diet,and systemic swallowing function training on the basis of the control group.The therapeutic effects,feeding conditions and VSD scale scores were compared after 1 month of intervention between the two groups.Results The drinking water test score in the observation group was lower than that in the control group,and the total effective rate of the swallowing function improvement was higher than that in the control group,the differences were statistically significant (P < 0.05).The FOIS score in the observation group was higher,and the score of VSD scale was lower than that in the control group,the differences were statistically significant (P < 0.05).Conclusion Drinking water test combined with swallowing training can effectively improve the swallowing function of patients with dysphagia after cerebral infarction,and is beneficial to the normal diet of the patients.

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