1.Inhibitory effect of SM-1 on human liver microsomal cytochrome P450 enzyme
Yanfen CHEN ; Jingxiu CHEN ; Meng SUN ; Junyao DING ; Zeneng CHENG ; Gaoyun HU ; Jinsong DING ; Qubo ZHU
Chinese Pharmacological Bulletin 2017;33(5):627-629
Aim To investigate the effect of SM-1 on seven main cytochrome P450(CYP450)in human liver microsomes.Methods Substrate or SM-1 was incubated with human liver microsomes for 30 min in vitro,and divided into control group and experimental group.The effects of SM-1 on the main phase I metabolic enzymes in human liver microsomes was detected by HPLC.Phenacetin,bupropion,paclitaxel,tolbutamide,omeprazole,dextromethorphan,testosterone were investigated as probe drugs.Results Inhibition rate of SM-1 on the classical substrate of human liver microsomal CYP was 0.05%,3.37%,0.08%,2.07%,4.20%,-0.15%and 10.84%,respectively.Conclusions SM-1 may have inhibitory effect on CYP3A4.Attention should be paid to the interaction of clinical drug induced by CYP enzyme inhibition.
2.Research on immune mechanism of Shengxian decoction in experimental autoimmune myasthenia gravis rats
Junyao XU ; Jie ZHU ; Yang CHENG ; Zhouye WU ; Yidi CHEN ; Baomei XIA ; Haoxin WU
Chinese Journal of Immunology 2016;32(10):1462-1466
Objective:To investigate the immune mechanism of Shengxian decoction in experimental autoimmune myasthenia gravis(EAMG) rats. Methods:Lewis rats were immunized with the rat sequence 97-116 of the AChRαsubunit(Rα97-116) in CFA, 25 of which were successful. They were randomly divided into 5 groups:EAMG model group,prednisone group(5. 4 mg/kg),Shengxian decoction low, medium, high dose groups ( dosage 2. 6 g/kg, 5. 2 g/kg, 10. 4 g/kg ) . Clinical symptoms, weight, and the decrement percentage of RNS(5 Hz) were evaluated,and ELISA were adopted to determine the titers of AChR Ab,TGF-β,IFN-γ,IL-2,IL-4 and IL-17 in serum. Results:After molding,the percentage of decrement of RNS in each group noticeably increased by more than 10% in comparison with that in the CFA control group ( P<0. 01 or P<0. 05 ) . At the same time, they were also subjected to progressive decreasing weight and typical myasthenia symptoms,showing the successful molding. With medication,the decrement percentage of RNS of rats in the groups with low,medium and high dose of Shengxian decoction were all on obvious decline with alleviated weight decrease (P<0. 01),testifying to the symptom improvement. Compared with the CFA control group,the groups with low,medium and high dose of Shengxian decoction were coupled with decreasing AChR Ab content(P<0. 05),rising TGF-βlevel and reducing IFN-γ,IL-2,IL-4 and IL-17 level(P<0. 01 or P<0. 05). Conclusion: Shengxian decoction can turn the decrement percentage of RNS around,improve the progressive weight decrease in EAMG rats and increase the weight gains. By up-regulating the TGF-βlevel,lowering IFN-γ,IL-2,IL-4 and IL-17 level,preventing B cells from producing AChR Ab and reducing the content of AChR Ab in serum,it will soothe the damage of NMJ to AChR and cure EAMG.
3. Imaging study of second sacral alar-iliac screw placement in adult degenerative scoliosis
Bing WU ; Kai SONG ; Zhaohan WANG ; Junyao CHENG ; Pengfei CHI ; Zheng WANG
Chinese Journal of Orthopaedics 2019;39(16):1013-1019
Objective:
To discuss the imagingcharacteristics of S2AI screw trajectory in ADS patients.
Methods:
Forty patients with degenerative scoliosis were scanned with Simens Sliding 40-slice spiral CT scanner. Three-dimensional scanning and reconstruction were performed in these patients with the scanning range including thoracolumbar spine, lumbar spine, lumbosacral region, pelvis and bilateral hip joints. The base of the lateral sacral crest on the midline between the lower edge of S1 dorsal foramina and the upper edge of S2 dorsal foramina was the starting point. The placement plane of S2AI screw trajectory was determined from the starting point to the lower margin of anterior inferior iliac spine. A 10mm diameter screw was the design template. A circle with a diameter of 5 mm as the center of the lowest point of the ilium inner cortex was made, and a tangent line from the starting point to the outer diameter of the circle (the inner part of the ilium) was selected as the axis of the screw trajectory. The lateral angle and the length of the axis of the screw trajectory and iliac width were measured in transverse plane. The caudal angle, the distance from the axis of the screw trajectory to iliosciatic notch, and the caudal angle, the distance from the axis of the screw trajectory to the upper edge of the acetabulum were measured in sagittal plane. These parameters were recorded and analyzed.
Results:
The trajectory length of S2AI screw in ADS patients was 12.00±0.99 cm, the lateral angle was 41.24°±3.92°, the caudal angle was 27.73°±6.45°, and the distance from the axis of the screw trajectory to iliosciatic notch was 1.05±0.81 cm, the distance from the axis of the screw trajectory to the upper edge of the acetabulum was 1.85 ± 0.33 cm, and the iliac width was 2.12±1.65 cm. The trajectory length, lateral angle, caudal angle, distance from the axis of the screw trajectory to iliosciatic notch, distance from the axis of the screw trajectory to the upper edge of the acetabulum and iliac width of S2AI screw was respectively 12.40±0.83 cm, 39.47°±1.76°, 28.00°±6.39°, 1.08±0.32 cm, 1.76±0.34 cm, 2.26±0.25 cm in male patients, and was respectively 11.75±1.01 cm, 42.30°±4.48°, 27.56°±6.61°, 1.21±1.00 cm, 1.90±0.32 cm, 2.04±0.18 cm in female patients. The screw length and lateral angle had statistically difference between male and female patients(
4.The application of robotic nephrectomy, work bench surgery with robotic kidney autotransplantation in nephron-sparing surgery of complex renal tumors
Yang FAN ; Jun DONG ; Qiang ZU ; Xin MA ; Hongzhao LI ; Qiang ZHU ; Junyao DUAN ; Xinning WANG ; Baojun WANG ; Cheng PENG ; Xu ZHANG
Chinese Journal of Urology 2019;40(5):340-345
Objective To investigate the safety and feasibility of robotic nephrectomy,work bench surgery with robotic kidney autotransplantation in the treatment of complex renal tumors.Methods The clinical data of 5 patients with renal tumors admitted from January 2018 to July 2018 were analyzed retrospectively.There were 4 males and 1 females.The median age was 49 years old,ranging 32-66 years.The median body mass index was 25.6 kg/m2,ranging 21.1-27.8 kg/m2.Serum creatinine level was 87.2 μmol/L,ranging 78.0-88.9μmol/L before bench surgery.5 patients had multiple bilateral renal tumors and had undergone laparoscopic or robotic partial nephrectomy on the contralateral kidney.For bench surgery kidney,4 cases were on the left side and 1 case was on the right side.Each kidney has more than 2 separate tumors,combined with complete endophytic tumors,tumors larger than 7 cm in diameter or hilar tumors.5 patients were all performed robotic nephrectomy,work bench partial nephrectomy with robotic kidney autotransplantation under general anesthesia.The patient was first in a lateral decubitus position for robotic nephrectomy,and the kidney was removed through a median 6 cm periumbilical incision.After kidney removal,kidney tumors were resected and kidney was reconstructed on a hypothermic working table.Then the kidney was packed in a plastic bag,filling with ice slush.The corresponding parts of the plastic bag were cut to expose the renal artery and vein.Finally,the patient was moved to lithotomy position with Trendelenburg tilt of 20°,and the autologous kidney wrapped in the plastic bag was placed through the previous periumbilical incision into the abdominal cavity for robotic kidney autotransplantation.The renal artery and vein were anastomosed end-to-side with the right external iliac artery and vein.The ureter and bladder were anastomosed.Autologous kidneys were placed in abdominal cavity in 4 cases,and placed in right iliac fossa with retroperitonealization in 1 case.Ice slush on the surface of the autologous kidney did not completely melt before the blood supply was restored during the operation,and the autologous kidney immediately urinated after the blood supply was restored.Results All surgeries were performed successfully without conversion to open surgeries.The total operation time was 460 min,ranging (415-645 min),the time of robotic nephrectomy was 120 min,ranging (74-300 min),the time of robotic kidney autotransphntation was 135 min,ranging(103-163 min),the warm ischemia time was 3 min,ranging (1.5-6.0 min),the cold ischemia time was 182 min,ranging(135-210 min),the rewarming time was 50 min,ranging(45-55 min),the estimated blood loss during operation was 100 ml,ranging(50-300 ml),and the hospital stay was 6 d,ranging(5-9 d).The number of resected tumors was 4,ranging(2-6).The pathology reveals clear cell carcinoma in 3 cases and chromophobe cell carcinoma in 2 cases.The surgical margins were all negative.The serum creatinine levels were 111.1 μmol/L (87-217.6 μ mol/L) and 106.1 μmol/L (87.1-172 μmol/L) on the 7th and 30th day after operation,respectively.One month after operation,CT showed that the function and morphology of the autologous kidneys were fine.No recurrence or metastasis was found in 5 patients during a median follow-up of 7 months,ranging (5.4-11.7 mon).Conclusions For patients with complex renal tumors who cannot undergo in situ partial nephrectomy,robotic nephrectomy,work bench surgery with robotic kidney autotransplantation can completely remove the tumors,maximize the preservation of renal function and minimize the trauma of patients,making the ultimate means of nephron-sparing surgery for patients with complex renal tumors more minimally invasive and safe.
5.Mechanism of Qianyang Yuyin Granules Regulating NR3C2/ROS/ERK Pathway to Alleviate Aldosterone-induced Podocyte Injury
Yin LI ; Fang YUAN ; Junyao XU ; Cheng NING ; Yixuan WANG ; Lichao QIAN ; Haitao LI ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):95-105
ObjectiveTo investigate the protective mechanism of Qianyang Yuyin granules (QYYY) on aldosterone-induced podocyte injury. MethodA total of 30 C57BL/6J mice were randomly divided into five groups: control group, model group, QYYY low dose (QYYY-L) group, QYYY high dose (QYYY-H) group, and spironolactone (SPL) group, with six mice in each group. Except for the control group, mice were implanted with osmotic minipumps and injected continuously with aldosterone (300 μg·kg-1·d-1) to induce renal injury. The drug administration group was given low and high doses (2.6, 5.2 g·kg-1·d-1) of QYYY and SPL (18 mg·kg-1·d-1) for 28 days. The renal pathological changes of mice were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of Nephrin, Desmin, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved Caspase-3, nuclear receptor subfamily 3 group C member 2 (NR3C2), extracellular regulated protein kinases (ERK), and phospho-ERK (p-ERK) in kidney tissue were detected by Western blot. The apoptosis levels of kidney tissue were detected by TdT-mediated dUTP nick and labeling (TUNEL) staining, and the superoxide dismutase (SOD) levels were detected. In vitro, the mice were divided into five groups: Control group, model group (aldosterone concentration of 200 nmol·L-1), QYYY-L group, QYYY medium dose (QYYY-M) group, and QYYY-H group (25, 50, and 100 mg·L-1). The effect of different concentrations of QYYY on the relative viability of aldosterone-induced podocytes was detected by cell proliferation and viability assay (CCK-8). The expressions of Nephrin, Desmin, Bax, Bcl-2, cleaved Caspase-3, NR3C2, and p-ERK/ERK were detected by Western blot. AnnexinV-FITC/PI flow cytometry was used to detect the apoptosis levels of podocytes. Reactive oxygen species (ROS) in podocytes were observed by DCFH-DA. ResultCompared with the control group, the model group showed structural pathological changes and fibrotic conditions in the kidney, increased apoptosis levels (P<0.01), and decreased SOD levels (P<0.01). Aldosterone concentration at 200 nmol·L-1 showed a significant decrease in podocyte activity (P<0.05). Podocytes in the model group showed structural pathological changes, disordered arrangement of intercellular microfilaments, increased apoptosis levels (P<0.01), and increased intracellular ROS levels (P<0.01). The protein expressions of Nephrin, Bcl-2, and p-ERK/ERK in kidney tissue and podocytes were decreased (P<0.05, P<0.01). The protein expressions of Desmin, Bax, cleaved Caspase-3, and NR3C2 were increased (P<0.05, P<0.01). Compared with the model group, QYYY alleviated the structural damage and fibrosis of the kidney, decreased the apoptosis levels (P<0.05, P<0.01), and enhanced the SOD content of the kidney (P<0.05, P<0.01). QYYY improved the activity of podocytes (P<0.05, P<0.01), restored the foot process structure of podocytes, and decreased apoptosis levels (P<0.01) and ROS levels of podocytes (P<0.01). The protein expressions of Nephrin, Bcl-2, and p-ERK/ERK in kidney tissue and podocytes were increased (P<0.05, P<0.01), and the protein expressions of Desmin, Bax, cleaved Caspase-3, and NR3C2 were down-regulated (P<0.05, P<0.01). ConclusionQYYY improves aldosterone-induced podocyte injury by regulating the NR3C2/ROS/ERK pathway.