1.The value of 125iodine implantation combining transcatheter arterial chemoembolization to prevent digestive tract bleeding in patients with portal vein tumor thrombus in primary hepatocellular carcinoma
Li JIANG ; Dongming HAN ; Hongtao HU ; Junli MA ; Yan ZHAO ; Hailiang LI ; Chenyang GUO ; Quanjun YAO
Chinese Journal of Radiology 2016;50(10):784-788
Objective This study was to investigate the value of CT guided 125iodine implantation combining transcatheter arterial chemoembolization(TACE) to prevent digestive tract bleeding in patients with portal vein tumor thrombus in primary hepatocellular carcinoma. Methods Forty patients with portal vein tumor thrombus which were diagnosed to have primary hepatocellular carcinomas by diagnostic criteria of Chinese Anti-Cancer Association were collected prospectively. They were divided into the treatment group and the control group, with 20 patients in each group. The treatment group was treated by TACE for hepatic tumor and 125iodine seed implantation for portal vein tumor thrombus, while the control group was treated by TACE for hepatic tumor and only given β-blockers medicines after treatment. Intraoperative and postoperative surgery-related complications were observed. Three months after surgery, enhanced abdominal CT scanning was performed to evaluate treatment effects which were divided into complete response (CR), partial response (PR), and progressive disease (PD) and stable of disease (SD), and the local tumor control rates were calculated. The bleeding rates and mortality after 3 months, 6 months, 12 months were recorded. Treatment effects of the two groups were compared with continuously correction Chi-square test, bleeding rates were compared with Fisher test, and survival rates were analyzed with Kaplan-Meier survival curve and compared with Log-rank test. Results Overall the 40 patients were treated successfully without serious surgery-related complications. In the treatment group, there were 8 patients with PR, 6 with SD and 6 with PD, and the local control rates were 40% (8/20). In the control group, there were 1 patient with PR, 6 patients with SD and 13 with PD. The difference of the local control rates was statistically significant (χ2=5.161, P=0.023).The bleeding rates at 3, 6 and 12 months were 2, 2 and 3 cases in the treatment group, for control group they were 2, 6 and 10 cases respectively. There was no statistical difference between the 3 months and 6 months bleeding rates (P values were 1.000 and 0.235), but for 12 months bleeding rates, the difference was statistically significant (P=0.041).The 1 year cumulative survival rates of the treatment group and control group were 70% (14/20) and 40% (8/20), and the difference was statistically significant (χ2=4.675, P=0.031). Conclusion The treatment of 125iodine implantation combining transcatheter arterial chemoembolization in patients with portal vein tumor thrombus in primary hepatocellular carcinoma can reduce variceal bleeding rate and improve survival rate.
2. Interleukin-17-mediated inflammation promotes nonalcoholic fatty liver disease in mice with regulation of M1-type macrophage polarization
Yi YANG ; Chenyang HAN ; Qiaobing GUAN ; Shuiliang RUAN
Chinese Journal of Hepatology 2018;26(12):916-921
Objective:
To study the mechanism of interleukin (IL)-17 in mice with non-alcoholic fatty liver disease for promoting M1-type macrophage polarization to exacerbate liver inflammation, and to provide references for the mechanism of NAFLD occurrence and development.
Methods:
A mouse model of NAFLD was constructed by high-fat diet. Mice were divided into control group, model group, IL-17 group, and anti IL-17 group. Histopathological changes of the liver were observed by HE staining. The serum levels of ALT and AST in peripheral blood of mice was detected by chemical colorimetry. Macrophages labeled with F4/80-PE, CD11C-FITC was designated as M1-type macrophages, those labeled with F4/80-PE, and CD206-APC was designated as M2-type macrophages. The proportion of M1 and M2 macrophages infiltrated into the liver tissues of mice were measured by flow cytometry. CD168 expression level of liver tissues was detected using immunohistochemistry. Protein and mRNA levels of the marker molecules (iNOS, TNF-alpha and IL-6) of M1 macrophages were detected using ELISA and RT-Q PCR. Western blot was used to detect the protein expression of JAK-STAT signal pathway and the expression level of MCP-1. Data were analyzed using one-way ANOVA and t-test.
Results:
High-fat diet NAFLD mice model was successfully constructed. IL-17 had increased the proportion of M1 macrophages in mice liver tissues and decreased the proportion of M2 macrophages (
3.Effects of CD68 + CD163 + M2 macrophages on tumor angiogenesis in hepatocellular carcinoma
Chenyang HAN ; Yi YANG ; Jin WANG ; Li GUO
Chinese Journal of Microbiology and Immunology 2020;40(4):283-289
Objective:To study the effects of CD68 + CD163 + M2 macrophages on promoting tumor angiogenesis in hepatocellular carcinoma. Methods:CD68 + M0 macrophages in human spleen tissues were separated by mechanical grinding and magnetic bead separation and used to induce CD68 + CD163 + M2 macrophages in vitro with the presence of IL-4 and IL-13. CD68 + M0 and CD68 + CD163 + M2 macrophages were respectively co-cultured with human umbilical vein endothelial cells (HUVEC) in vitro. CCK-8 assay and scratch test were performed to detect the viability and migration ability of HUVEC. Tube formation assay was used to analyze in vitro angiogenesis. Expression of vascular endothelial growth factor receptor 2 (VEGFR2), Notch1 and Dll4 in HUVEC was detected by Western blot. Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of vascular endothelial growth factor (VEGF) and IL-8 in media. BALB/c nude mice were used to construct HepG2 hepatoma model. CD68 + M0 and CD68 + CD163 + M2 macrophages were respectively injected into the mice. Expression of CD105 in tumor tissues was detected by immunohistochemistry. Expression of VEGF, VEGFR2, Notch1 and Dll4 in tumor tissues was detected by Western blot. Results:(1) IL-4 and IL-13 could induce CD68 + M0 macrophages to differentiate into CD68 + CD163 + M2 macrophages. (2) In the cell experiments, CD68 + M0 macrophages did not significantly promote the angiogenesis of HUVEC, and there was no significant change in the level of VEGF, VEGFR2, Notch1, Dll4 or IL-8. CD68 + CD163 + M2 macrophages could promote the in vitro tube formation of HUVEC, which was related to the activation of VEGF-VEGFR2-Notch1/Dll4 signaling pathway. (3) In the animal experiments, CD68 + CD163 + M2 macrophages could promote the expression of CD105, the formation of tumor vessels and the expression of VEGF-VEGFR2-Notch1/Dll4 signals. Conclusions:CD68 + CD163 + M2 macrophages could promote the formation of tumor vessels in hepatocellular carcinoma by secreting angiogenic factors including VEGF and activating VEGF-VEGFR2-Notch1/Dll4 signals.
4.Analgesic mechanism of minocycline inhibiting activation of glial cells in rat models of trigeminal neuralgia
Yi YANG ; Chenyang HAN ; Li GUO ; Qiaobin GUAN
Chinese Journal of Neuromedicine 2018;17(7):656-661
Objective To study the mechanism of minocycline inhibiting inflammatory reaction of trigeminal ganglion glial cells in trigeminal neuralgia rats,and provide reference and support for treatment of trigeminal neuralgia.Methods (1) The rat models of trigeminal neuralgia were established by laser chemical induction oftrigeminal nerve injury.Thirty SD rats were randomly divided into sham-operated group,model Ⅰ group,minocycline group (intragastric administration of 50 μg minocycline for 7 d,n=10).The threshold of mechanical pain was measured in the facial nerve areas of rats.The protein and mRNA expressions of nuclear transcription factor (NF)-κB and interleukin (IL)-1β in the trigeminal ganglion were detected,the activation of satellite glial cells was observed by glial fibrillary acidic protein (GFAP) staining,and immunohistochemical staining was used to detect NF-κB level.(2) The inflammatory models of glial cells were established with nitroglycerin;and trigeminal glial cells from the SD rats were cultured in vitro;the cell models were divided into control group,model Ⅱ group,low-dose minocycline group (15 μmol/L),and high-dose minocycline group (30 μmol/L);the expressions of NF-κB and IL-1β in cells were detected.Fluo-3/AM probe load was used to observe the concentration changes of calcium ions in the glial cells.Results (1) The threshold of pain in trigeminal neuralgia of minocycline group was significantly higher than that of model Ⅰ group (P<0.05);the protein and mRNA expressions of NF-κB and IL-1β in the minocycline group were significantly decreased as compared with those in model Ⅰ group (P<0.05);weak NF-rB expression was noted in the sham-operated group,strong NF-κB expression was noted in the model Ⅰ group,and that in the minocycline group was obviously decreased as compared with that in model Ⅰ group;number of GFAP positive cells in the minocycline group was significantly smaller as compared with the model Ⅰ group (P<0.05).(2)The protein and mRNA expressions of NF-κB and IL-1β in the low-dose minocycline group and high-dose minocycline group were significantly decreased as compared with those in the model Ⅱ group (P<0.05);and the concentration of calcium ions in astrocytes of the low-dose minocycline group and high-dose minocycline group was significantly decreased as compared with that of model Ⅱ group (P<0.05).Conclusion Minocycline can alleviate pain in trigeminal neuralgia rats by inhibiting the activation of satellite glial cells and decreasing the levels of inflammatory factors NF-κB and IL-1β.
5.Effect of intestinal bacteria on motor function and its mechanism in amyotrophic lateral sclerosis mice
Qiaobing GUAN ; Xiaoling ZHANG ; Shuiliang RUAN ; Chenyang HAN
Chinese Journal of Neuromedicine 2019;18(2):115-121
Objective To study the effect of intestinal bacteria on motor ability of amyotrophic lateral sclerosis (ALS) mice models and its mechanism. Methods Twenty wild type C57BL/6J mice (WT group) and 20 SOD1-G93A transgenic ALS mice (ALS group) were selected as the research subjects. (1) Ten mice in both WT group and ALS group were selected, respectively; 5 mice in each group were fed in SPF environment, and the remaining 5 mice were fed in aseptic environment; they were defined as WT+SPF group, WT+aseptic group, ALS+SPF group and ALS+aseptic group. (2) Ten mice in WT group and ALS group were fed in sterile environment; 5 mice in each group were transplanted with fecal bacteria, and the remaining 5 mice were not interfered; they were defined as WT+transplantation group, WT+non-transplantation group, ALS+transplantation group and ALS+non transplantation group. The grip strength of mice was measured by grip force meter, the motor coordination ability of mice was tested by roller treadmill and rotating rod test, the number of motor neurons in the anterior horn of spinal cord was measured by Nissl staining, the expression of microglia activation marker ionic calcium junction protein (IBA-1) in spinal cord tissues was detected by immunohistochemical staining, and the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in spinal cord tissues were detected by Western blotting; the β-N-methylamino-L-alanine (BMAA) expression was detected by high performance liquid chromatography-tandem mass spectrometry. Results (1) The grip strength, drop latency and drop time of ALS+aseptic mice were significantly higher than those of ALS+SPF mice, the number of Nissl-stained positive cells was significantly larger than that of ALS+SPF mice, the number of IBA-1 positive cells was significantly smaller than that of ALS+SPF mice, the levels of TNF-α and IL-6 protein expressions and BMAA concentration were statistically lower than those of ALS+SPF mice (P<0.05). (2) The grip strength, drop latency and drop time of ALS+transplantion mice were significantly lower than those of ALS+non-transplantation mice, the number of Nissl-stained positive cells was significantly smaller than that of ALS+non-transplantation mice, the number of IBA-1 positive cells was significantly larger than that of ALS+non-transplantation mice, the TNF-α and IL-6 protein expressions and BMAA concentration were significantly higher than those of ALS+non-transplantation mice (P<0.05). Conclusion Imbalance of intestinal bacteria homeostasis can decrease the motor ability of ALS mice, which is related to the activation of microglia.
6.Helper T cell Th9 and its cytokine interleukin-9 in peripheral blood of patients with Parkinson's disease
Yi YANG ; Chenyang HAN ; Li GUO ; Qiaobing GUAN
Chinese Journal of Neurology 2018;51(3):171-174
Objective To investigate the proportion of helper T cell subset Th 9 and the expression of its cytokine interleukin-9(IL-9)in Parkinson's disease(PD)and the clinical significance.Methods Seventy-two patients diagnosed with PD between January 2016 and June 2017 and 20 healthy volunteers in the same period were selected.The PD patients were staged according to the Hoehn-Yahr(H-Y)staging method,21 in stage one,19 in stage two,18 in stage three,11 in stage four,and three in stage five.The proportion of Th9 subset in peripheral blood of PD patients and healthy volunteers was measured by flow cytometry.The expression of IL-9 in peripheral blood of PD patients and healthy volunteers was measured by enzyme-linked immunosorbent assay.Results The proportion of Th9 cells in peripheral blood of PD patients(1.27%±0.34%)was significantly higher than that of healthy volunteers(0.61%±0.11%,t=8.530,P<0.05),and the higher stage of PD,the higher proportion of Th9,suggesting that the proportion of Th9 was related to the PD staging.IL-9 was also highly expressed in PD patients((16.04 ±2.94) pg/ml)and had statistically significant difference compared with healthy volunteers((7.53 ±0.70)pg/ml;t=12.781,P<0.05).IL-9 was similar to Th9, the higher stage of PD, the higher expression of IL-9. Conclusion The proportion of Th9 cells and the expression of IL-9 in peripheral blood of patients with PD increased significantly,having a significant relationship with the H-Y staging of PD.
7.Effects of dl-3-n-butylphthalide on angiogenesis of human umbilical vein endothelial cells under ischemia/hypoxia condition:in vitro experiment and its mechanism
Yi YANG ; Qiaobing GUAN ; Li GUO ; Xiaoling ZHANG ; Chenyang HAN
Chinese Journal of Neurology 2018;51(6):464-469
Objective To investigate the effects of dl-3-n-butylphthalide ( NBP) on angiogenesis of human umbilical vein endothelial cells ( HUVEC) in vitro under ischemia/hypoxia and the correlation with vascular endothelial growth factor/vascular endothelial growth factor receptor 2 ( VEGF/VEGFR2 )-Notch1/Dll4 signaling pathway .Methods The control group , ischemia/hypoxia group , and ischemia/hypoxia +NBP group ( high dose group and low dose group ) were set up after HUVEC subculture . The cell concentration was adjusted to be 1 ×105/ml, and each group was randomly added 1 ml (1 ×105 cells in each group).Both of the ischemia/hypoxia group and the ischemia/hypoxia +NBP group were cultured under the condition of ischemia and hypoxia .The NBP concentrations of the high and low dose groups were 20 μmol/L and 5 μmol/L respectively.The cell viability of each group was detected by cell counting kit-8, and cell scratch test was used to detect the migration ability of the cells in each group .The cell formation ability of each group was examined by in vitro angiogenesis assay.Western blotting was used to detect the expressions of receptor proteins VEGFR2, Notch1 and Dll4,and mRNA expressions of VEGF, VEGFR2, Notch1 and Dll4 were detected by real-time quantitative PCR.Results NBP increased the survival rates of HUVEC under ischemia/hypoxia condition.In the low dose group, the survival rates of HUVEC at 6, 12, 24, 48 h were 78.6% ±3.0%, 59.6% ±5.3%, 44.6% ±4.2%, 38.2% ±4.3%, respectively, significantly higher than that in the ischemia/hypoxia group (75.2%±5.8%, 53.2%±4.8%, 36.2%± 7.8%, 22.5%±4.1%;t=4.513, 6.231, 9.322, 9.674; P=0.021, 0.018, 0.026, 0.015).In the high dose group, the survival rates of HUVEC at 6, 12, 24, 48 h were 88.6%±6.3%, 67.5%±5.4%, 53.3%±4.2%, 46.3%±3.9%, respectively , also significantly higher than that in the ischemia/hypoxia group (t=8.123, 11.211, 12.312, 14.154;P=0.001, 0.002, 0.001, 0.001).The mobility of the low dose group was 52.3%+4.2%, with statistically significant difference compared with that in the ischemia /hypoxia group ( 18.5% ±3.2%) and the control group ( 22.3% ±4.1%; t=18.324, 15.183; P=0.000, 0.000).The mobility of the high dose group was 87.5%±5.2%, also with statistically significant difference compared with that in the ischemia/hypoxia group and the control group ( t=22.142, 19.341;P=0.000, 0.000).NBP increased the protein and mRNA expression of VEGF , VEGFR2, Notch1 and Dll4.The relative expression of VEGFR2, Notch1 and Dll4 in the low dose group was 1.12 ±0.17, 0.35 ± 0.07 and 0.42 ±0.08, respectively, with statistically significant difference compared with that in the ischemia/hypoxia group (0.82 ±0.05, 0.30 ±0.03, 0.32 ±0.04;t=6.120, 2.123, 4.112;P=0.000, 0.020, 0.003).The relative expression of VEGFR2, Notch1 and Dll4 in the high dose group was 1.30 ± 0.15, 0.41 ±0.10 and 0.48 ±0.11, respectively, also with statistically significant difference compared with that in the ischemia/hypoxia group ( t=8.122, 3.851, 5.130; P=0.000, 0.000, 0.001 ) .The mRNA expressions of VEGF , VEGFR2, Notch1 and Dll4 in the low dose group were 0.43 ±0.08, 0.41 ± 0.05, 0.38 ±0.03 and 0.36 ±0.04, respectively, with statistically significant difference compared with that in the ischemia/hypoxia group (0.28 ±0.03, 0.34 ±0.04, 0.27 ±0.03, 0.19 ±0.04;t=3.122, 3.825, 4.311, 5.211; P=0.000, 0.006, 0.001, 0.000).And the mRNA expressions of VEGF, VEGFR2, Notch1 and Dll4 in the high dose group were 0.58 ±0.05, 0.50 ±0.06, 0.41 ±0.05, 0.52 ±0.06, respectively, also with statistically significant difference compared with that in the ischemia /hypoxia group (t=4.225, 4.872, 5.311, 8.220;P=0.000, 0.000, 0.000, 0.000).Conclusions NBP can promote HUVEC to form blood vessels under ischemia/hypoxia condition , the mechanism of which may be related to the activation of VEGF/VEGFR2-Notch1/Dll4 signaling pathway .It may be one of the mechanisms that NBP improves cerebral microcirculation in acute ischemic stroke .
8.Therapeutic effect of continuous arterial catheter directed thrombolysis on lower limb arterial ischemic disease
Jie FANG ; Yongbao ZHANG ; Han LI ; Chengjia QU ; Lequn TENG ; Chenyang SHEN
International Journal of Surgery 2019;46(7):477-480
Objective To investigate the clinical efficacy of continuous arterial catheter directed thrombolysis for ischemia disease of lower extremity.Methods Retrospective analysis of clinical data of 29 patients undergoing continuous arterial catheter directed thrombolysis from June 2016 to June 2018 in Department of Aortic and Vascular Surgery Center,Fuwai Hospital,CAMS&PUMC was conducted.There were 25 males and 4 females,aged (65.3 ± 11.2) years,with an age range of 51-81 years.The patients were diagnosed after admission and received continuous arterial thrombolysis.After thrombolytic therapy,estimate was conducted whether to place the stent further based on the result of angiographit.The patients' pain symptom relief,embolism,bleeding and other complications were observed in the 6 months,12 months and 24 months by telephone follow-up or outpatient review.Meanwhile,the patients improved the color Doppler ultrasound examination.Results The 21 patients were markedly effective,7 patients were effective,and 1 patient was ineffective in all the 29 patients who accepted the continuous arterial catheter directed thrombolysis therapy.Two of the patients developed distal toe arterial embilization during thrombolysis and improved after drug treatment.The total effective rate was 96.5% (28/29).Stents implant rate was 20.7% (6/29).The follow-up rate was 86.2% (25/29).No symptom relapse was observed.Conclusion Continuous arterial catheter directed thrombosis for ischemia disease of lower extremity is minimally invasive,safe and effective.
9.To study the correlation of peripheral blood F-box and WD repeat domain-containing domain protein7 and myeloid cell leukemia-1 expression levels with the prognosis of Icotinib administration in elderly patients with advanced non-small-cell lung cancer
Yi YANG ; Qiaobin GUAN ; Li GUO ; Chenyang HAN
Chinese Journal of Geriatrics 2018;37(8):888-891
Objective To study the correlation of the prognosis of Icotinib administration with the expression levels of F-box and WD repeat domain-containing 7(FBW7) and myeloid cell leukemia-1 (MCL-1) in peripheral blood in elderly patients with advanced non-small-cell lung cancer.Methods A total of 76 patients aged 60 years or over diagnosed with non-small-cell lung cancer(NSCLC) with EGFR-sensitive mutations and under Icotinib treatment were enrolled in this study.FBW7 and MCL-1 mRNA expression levels in peripheral blood were detected by real-time quantitative PCR(RT-QPCR).The correlation of FBW7 and MCL-1 expression levels with clinical and histological parameters,overall survival (OS),and progression-free-survival (PFS) was analyzed.Results The FBW7 expression level and the MCL-1 expression level were negative correlated(r =-0.37,P <0.001).High FBW7 expression levels and low MCL-1 expression levels in peripheral blood were associated with improved therapeutic efficacy of Icotinib (P<0.001) and extended OS and PFS.Cox regression analysis showed that the expression levels of FBW7 and MCL-1 in peripheral blood were independent influencing factors for OS and PFS.Conclusions Patients with high FBW7 expression levels and low MCl-1 expression levels are more likely to benefit from Icotinib treatment.Expression levels for either factor can be used as a predictive indicator for the effectiveness of Icotinib and provide guidance for its clinical use.
10.Single-docking transperitoneal robotic-assisted nephroureterectomy: surgical techniques and outcomes
Chenyang WANG ; Hao LIU ; Jinli HAN ; Chun JIANG ; Jian HUANG
Chinese Journal of Urology 2020;41(2):85-89
Objective To introduce and discuss the efficacy of a new technique to perform transperitoneal single-docking robot-assisted laparoscopic nephroureterectomy (RNU).Methods A total of 44 patients diagnosed with urothelial neoplasm of the renal pelvis or were investigated from January 2016 to November 2019.RNU was performed by a single surgeon.Among the 44 patients,31 were male,and 13 were female.The median age was 63 (IQR:58-71).The median body mass index (BMI) was 23.08 (IQR:21.55-24.60) kg/m2.All operations were performed with general anesthesia.The patients were positioned 80 degrees flank with the diseased side up,and the head was tilted 10 degrees downwards.The camera port was placed one finger lateral to the umbilicus.For the right-sided tumors,robotic arm 1 was inserted through the trocar on the right pararectus line,8 cm above the umbilicus,and robotic arm 2 was inserted through the trocar on the same line,8 cm below the umbilicus.Assistant trocar 1 was placed where the anterior midline joins the perpendicular bisector of the camera port and robotic 2,and assistant trocar 2 was placed below the xiphoid process.For the left-sided tumors,all trocars were centrosymmetric to that of the right-sided tumors,except that assistant port 2 was placed 3 finger width above the pubic symphysis.The peritoneum was incised along the Toldt line,and the inferior vena cava was isolated (for left sided tumor,the abdominal aorta was isolated instead).The renal artery and vein were clipped with Hem-o-lok and ligated,and the kidney were isolated.The ureter was identified and isolated downwards across the common iliac artery and then clipped distal to the tumor site.The bladder cuff was resected and sutured under the laparoscopy.Results The median operation time was 145 (IQR:130-175) min,with the median console time of 119 (IQR:108.5-136.0) min,the anastomosis of bladder cuff of 12 min,and the median estimated blood loss of 50 (20-100)ml.After the surgery,6 Clavien-Dindo grade 2 complications occurred,including 2 chylous leakage,1 hemostasis,1 blood transfusion,1 deep vein thrombus,and 1 acute coronary syndrome.The median length of stay (LOS) was 8 (IQR:6.5-10.0) d.The median length of follow-up was 12 months.In total,5 patients were dead,including 3 cancer-specific death.Four recurrence occurred and caused 3 death.The 2-year overall survival and progression-free survival were 68.2% and 77.9%,respectively.Conclusions The technique of RNU with simultaneous bladder cuff excision (BCE).Our technique improved the surgical outcome.The perioperative complication rate was low,and the short-term survival outcomes were satisfactory.