1.Effect and mechanism of cytochrome P450 1A1 on regulating phagocytosis of macrophage
Lixing TIAN ; Linghui WAN ; Junyu ZHU ; Huaping LIANG
Chinese Critical Care Medicine 2023;35(2):158-163
		                        		
		                        			
		                        			Objective:To explore the effect and mechanism of cytochrome P450 1A1 (CYP1A1) on regulating phagocytosis of macrophage treated with Escherichia coli ( E.coli). Methods:① The mouse leukemia cells lines of monocyte macrophage RAW264.7 (RAW) were cultured in vitro and treated with 30 multiplicity of infection (MOI) dosages of E.coli for 40 minutes, glycerin control group was set up to observe the change of CYP1A1 during infection. ② The RAW cells with CYP1A1 overexpression (CYP1A1/RAW) and knock out (CYP1A1 KO/RAW) were cultured in vitro and treated with 30 MOI E. coli for 40 minutes, while the negative controlled RAW cells (NC/RAW) were established as control to observe the relationship between cell phagocytosis and CYP1A1 expression, and the effect of CYP1A1 on phagocytic receptor [scavenger receptor-A (SR-A)] and its signal pathway [mitogen-activated protein kinase (MAPK) pathway]. ③ NC/RAW and CYP1A1 KO/RAW cells were cultured in vitro and pretreated with 1 μmol/L extracellular signal-regulated kinase (ERK) inhibitor (U0126) for 2 hours, and then treated with 30 MOI E.coli for 40 minutes, phosphate buffered solution (PBS) control group was set up to observe whether the effect of CYP1A1 on phagocytosis through controlled the MAPK pathway. ④ The RAW cells were cultured in vitro and pretreated with 100 nmol/L CYP1A1 hydroxylase active product 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] for 2 hours, and then treated with 30 MOI E.coli for 40 minutes, and PBS control group was set up to observe whether the effect of CYP1A1 on phagocytosis was related to CYP1A1 hydroxylating metabolite. ⑤ The RAW cells with overexpression CYP1A1 hydroxylase-activity mutation (CYP1A1m/RAW) were cultured in vitro and treated with 30 MOI E.coli for 40 minutes, the CYP1A1/RAW cells were set up as control group to observe whether the effect of CYP1A1 on phagocytosis was related to CYP1A1 hydroxylase-activity. Results:① Compared with glycerin control group, CYP1A1 mRNA expression was significantly increased by E.coli stimulation (2 -ΔΔCt: 7.79±0.71 vs. 1.00±0.00, P < 0.05), indicating that CYP1A1 might participate in regulating infection progress. ② Compared with NC/RAW cells, the number of E.coli colonies phagocytized by CYP1A1/RAW cells was significantly decreased after 40 minutes of E.coli stimulation (×10 3 CFU/mL: 4.67±3.06 vs. 15.67±5.03, P < 0.05), while CYP1A1 KO/RAW cells had a significant increase in the number of E.coli colonies phagocytized (×10 3 CFU/mL: 46.00±5.29 vs. 15.67±5.03, P < 0.05), suggesting that CYP1A1 might negatively control macrophage phagocytosis function. Meanwhile, compared with NC/RAW cells, the expression of SR-A mRNA in CYP1A1/RAW cells was significantly down-regulated (2 -ΔΔCt: 0.31±0.03 vs. 1.00±0.00, P < 0.05), and the activation level of ERK was significantly reduced. However, the expression of SR-A mRNA in CYP1A1 KO/RAW cells was significantly up-regulated (2 -ΔΔCt: 3.74±0.25 vs. 1.00±0.00, P < 0.05), and the activation of ERK was enhanced, indicating that CYP1A1 could negatively regulate phagocytic receptors and their signaling pathways.③ Compared with PBS, U0126 pretreatment significantly inhibited the CYP1A1 knockout induced upregulation of SR-A mRNA expression (2 -ΔΔCt: 0.62±0.05 vs. 4.38±0.39, P < 0.05) and ERK activation, and inhibited the enhancement of phagocytosis in macrophages induced by CYP1A1 knock out [ E.coli colonies phagocytized by cells (×10 3 CFU/mL): 12.67±1.15 vs. 45.33±4.16, P < 0.05], suggesting that CYP1A1 inhibited macrophage phagocytosis function by regulating ERK activation. ④ Compared with PBS, the phagocytosis of RAW cells pretreated with 12(S)-HETE did not change significantly [ E.coli colonies phagocytized by cells (×10 3 CFU/mL): 17.00±1.00 vs. 16.33±2.52, P > 0.05], suggesting that CYP1A1 might not control phagocytosis function by its hydroxylase-activity metabolism 12(S)-HETE. ⑤ Compared with CYP1A1/RAW cells, there was no significant change in the phagocytic function of CYP1A1m/RAW cells [ E.coli colonies phagocytized by cells (×10 3 CFU/mL): 3.67±1.15 vs. 3.33±0.58, P > 0.05], suggesting that CYP1A1 might not control phagocytosis function by its hydroxylase-activity. Conclusion:CYP1A1 can negatively regulate the phagocytosis of macrophages by inhibiting the activation of ERK and reducing the expression of SR-A, but this regulatory effect is not related to the activity of CYP1A1 hydroxylase and its pro-inflammatory metabolism 12(S)-HETE.
		                        		
		                        		
		                        		
		                        	
2.Significance of expressions of HDGF、VEGF and mucin 5B in hepatolithiasis associated with intrahepatic cholangiocarcinoma
Jinhai LI ; Minghui ZHU ; Lixing SUN ; Qingfan PU ; Haifeng ZHANG ; Shenghua PAN
Chinese Journal of Hepatobiliary Surgery 2022;28(2):97-102
		                        		
		                        			
		                        			Objective:To study the roles of hepatoma-derived growth factor (HDGF), vascular endothelial growth factor (VEGF) and mucin 5B (MUC5B) in hepatolithiasis associated with intrahepatic cholangiocarcinoma (HICC).Methods:The clinical data and tissue specimens of 116 patients who underwent hepatectomy at the Third Affiliated Hospital of Wenzhou Medical University from October 1999 to October 2019 were retrospectively analyzed. There were 41 patients with HICC (the HICC group), 38 patients with intrahepatic cholangiolithiasis (the intrahepatic cholangiolithiasis group), and 37 patients with benign liver tumor who underwent hepatectomy (the control group). There were 47 males and 69 females, with age of (66.1±3.2) years old. The positive expressions of HDGF, VEGF and MUC5B in the three groups were compared. In 41 patients with HICC, the correlation between positive expressions of HDGF, VEGF and MUC5B with patients’ clinical characteristics were studied.Results:Compared with the control group, the positive expression rates of HDGF, VEGF and MUC5B in the HICC group and the intrahepatic cholangiolithiasis group were significantly increased, ( P<0.05). Compared with the intrahepatic cholangiolithiasis group, the positive expression rates of HDGF, VEGF and MUC5B in the HICC group were significantly increased ( P<0.05). Positive expression of VEGF in HICC patients was correlated with tumor differentiation, tumor local invasion, tumor length, tumor stage, tumor carbohydrate antigen CA19-9 level and lymph node metastasis ( P<0.05). Spearman correlation analysis showed that HDGF was positively correlated with VEGF expression in HICC tissues specimens ( r=0.935, P<0.01). Survival analysis showed that the cumulative survival rates (36.7%, 17.1%, 7.3%) of patients with positive expression of VEGF were significantly lower than that of patients with negative expression (51.2%, 26.8%, 19.5%) at 1, 3, 5 years after surgery ( P<0.01). The cumulative survival rate (34.1%, 17.1%, 4.9%) of patients with MUC5B positive expression were significantly lower than that of patients with negative expression (53.7%, 31.7%, 17.1%) at 1, 3, 5 years after surgery ( P<0.01). Conclusion:HDGF can be used as a reference indicator for early assessment of HICC. Overexpressions of VEGF and MUC5B can be used as important indicators for HICC in evaluating disease progression and prognosis.
		                        		
		                        		
		                        		
		                        	
3.Endovascular treatment of innominate artery stenosis or occlusion
Chengchao ZHANG ; Yuhao JIAO ; Yongquan GU ; Lianrui GUO ; Zhu TONG ; Lixing QI ; Shijun CUI ; Jianming GUO
Journal of Chinese Physician 2020;22(11):1640-1644
		                        		
		                        			
		                        			Objective:To explore the method and effect of endovascular treatment to innominate artery stenosis or occlusion.Methods:The data of 11 patients with stenosis or occlusion of innominate artery from January 2014 to November 2019 at Xuanwu Hospital of Capital Medical University were collected. All patients received endovascular treatment. We summarized the changes of clinical symptoms, surgical methods, perioperative complications, stent patency, and analyzed the changes in systolic blood pressure and peak blood flow velocity on the involving side.Results:All 11 patients underwent endovascular treatment. The surgical technique success rate was 100%. All patients were followed up. The follow-up time was 4-69 months, with an average of (30.1±23.4)months. 2 patients used cerebral umbrella during the operation. 1 patient was performed ipsilateral carotid endarterectomy, 1 patient underwent contralateral carotid stent implantation, 1 patient was diagnosed as severe stenosis of the innominate artery and left common carotid artery, and an innominate artery stent implantation was performed at one stage, left common carotid artery stent implantation was performed after half a year. We done operation from the femoral artery puncture approach (6 patients), brachial artery puncture approach (2 patients), axillary artery and femoral artery puncture approach (1 patients), and right common carotid artery and the femoral artery puncture approach (2 patients). 3 patients had in-stent restenosis at 6, 7and 12 months after stenting, respectively. 1 patient underwent balloon dilatation, and 2 patients underwent re-stent implantation. We have not do further intervention to 1 case of in-stent occlusion occurred 14 months after the stenting, for the clinical symptoms did not improve significantly. The clinical re-intervention rate in this group was 3/11, and the primary patency rate was 7/11. The secondary patency rate was 10/11. The symptoms of 10 patients were relieved and the weakness of right upper extremity was not significantly changed in 1 patient. No puncture point complications occurred in all patients, and no cerebral infarction occurred during the perioperative period. There were statistically significant differences in systolic blood pressure, blood pressure difference and peak blood flow velocity before and after the operation ( P<0.05). Conclusions:Endovascular treatment of innominate arterial stenosis or occlusion was safe and effective, and the appropriate surgical approach and plan should be selected according to the lesion characteristics and the whole body conditions.
		                        		
		                        		
		                        		
		                        	
4.Comparison of 68Ga-PSMA-617 and MRI in diagnosis and staging of primary prostate cancer
Sijuan ZOU ; Shuang SONG ; Lixing CHEN ; Jianyuan ZHOU ; Zhaoting CHENG ; Xiaohua ZHU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(12):710-715
		                        		
		                        			
		                        			Objective:To compare the performance of 68Ga-prostate specific membrane antigen (PSMA) PET/CT and MRI in preoperative diagnosis and staging of primary prostate cancer. Methods:Twenty-four patients with prostate cancer, who underwent preoperative 68Ga-PSMA PET/CT and prostate MRI in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2018 and December 2019, were retrospectively enrolled. The pathological and follow-up results were considered as the gold standard, and diagnostic efficiencies of the 2 imaging methods were compared per patient and per type of lesions (seminal vesicle invasion, bladder neck invasion, lymph node metastasis and bone metastasis). The χ2 test was used for data analysis. Results:Prostate cancer was confirmed by pathology in 24 patients, including 6 cases with both seminal vesicle and bladder neck invasion, 5 cases with seminal vesicle invasion and 3 cases with invasion of bladder neck. Gleason scores in patients were as follow: 7 in 9 patients, 8-9 in 15 patients. The detection rates of 68Ga-PSMA PET/CT and MRI for primary prostate cancer were both 100%(24/24). The sensitivity, specificity and accuracy of 68Ga-PSMA PET/CT and MRI for detecting seminal vesicle invasion were 10/11, 13/13, 95.8%(23/24) and 9/11, 11/13, 83.3%(20/24), respectively. The specificity and accuracy were significantly different ( χ2 values: 6.231, 13.470, both P<0.05). The sensitivity, specificity and accuracy of 68Ga-PSMA PET/CT and MRI for detecting bladder invasion, which were 7/9, 13/15, 83.3%(20/24) and 3/9, 14/15, 70.8%(17/24), respectively, were not significantly different( χ2 values: 1.285, 0.164, 2.880, all P>0.05). Furthermore, the sensitivity, specificity and accuracy of 68Ga-PSMA PET/CT for detecting pelvic lymph node metastasis were 11/11, 13/13 and 100%(24/24), respectively, and those of MRI for evaluating pelvic lymph node metastasis were 6/11, 11/13 and 70.8%(17/24), and the specificity of the 2 methods were significantly different ( χ2=6.231, P<0.05). All the 5 patients with pelvic bone metastasis were positive on 68Ga-PSMA PET/CT imaging, but only 2 of them were positive on MRI. Information from 68Ga-PSMA PET/CT changed pelvic TNM stage in 41.7%(10/24) patients who underwent MRI for initial staging. Conclusions:68Ga-PSMA PET/CT imaging and MRI can both accurately detect intermediate- to high-risk primary prostate cancer and seminal vesicle invasion. 68Ga-PSMA PET/CT imaging is superior to MRI for evaluating lymph nodes and bone metastasis. 68Ga-PSMA PET/CT provides high accuracy for preoperative diagnosing and staging intermediate- to high-risk prostate cancer.
		                        		
		                        		
		                        		
		                        	
5. Endovascular treatment to cerebral infarction combined with right aortic arch and Kommerell 's diverticulum: case report
Chengchao ZHANG ; Yongquan GU ; Lianrui GUO ; Lixing QI ; Zhu TONG ; Shijun CUI ; Jianming GUO ; Yiren LIU
Journal of Chinese Physician 2019;21(12):1774-1777
		                        		
		                        			 Objective:
		                        			To investigate the effect of endovascular treatment of cerebral infarction with right aortic arch and Kommerell's diverticulum.
		                        		
		                        			Methods:
		                        			Retrospective analysis was done to assess the treatment effect of a case from vascular surgery, Xuanwu Hospital of Capital Medical University. This case was diagnosed as cerebral infarction with right aortic arch and Kommerell's diverticulum.
		                        		
		                        			Results:
		                        			One month after the treatment of cerebral infarction, we successfully used the thoracic aortic stent to isolate the Kommerell's diverticulum. There were no operative complications occurred. The stent had good shape and smooth blood flow was seen in the stent.
		                        		
		                        			Conclusions
		                        			Endovascular treatment to cerebral infarction with right aortic arch and Kommerell's diverticulum is safe and feasible, and the clinical outcome requires further long-term follow-up. 
		                        		
		                        		
		                        		
		                        	
6.Targeted imaging and therapy of prostate cancer by radionuclide labeled small molecule inhibitors of prostate specific membrane antigen
Lixing CHEN ; Sijuan ZOU ; Xiaohua ZHU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(1):53-58
		                        		
		                        			
		                        			Prostate specific membrane antigen (PSMA) overexpresses in most prostate cancer (PCa) lesions and plays an important role in the early diagnosis and preoperative staging,clinical decision making,recurrence and metastasis detection as well as targeted therapy.Radionuclide (especially 68Ga and 177Lu) labeled multiple small molecule inhibitors of PSMA have been wildly used in SPECT,PET imaging on PCa,and play an important role in the treatment of metastatic castration resistant prostate cancer (mCRPC).This review summarizes the development in these fields.
		                        		
		                        		
		                        		
		                        	
7.Clinical study on surgical treatment of lower extremity chronic ischemia caused by arteriosclerosis obliterans of lower extremity-analysis of 4602 cases
Jianming GUO ; Lianrui GUO ; Lixing QI ; Shijun CUI ; Zhu TONG ; Zhiwen CAI ; Yuehao XING ; Yongquan GU
Journal of Chinese Physician 2018;20(12):1787-1791
		                        		
		                        			
		                        			Objective The incidence of chronic lower limb ischemia caused by arteriosclerotic obliteration of lower extremities is increasing recent years and there is a high risk of amputation and mortality.This study was to find out the changes in a single center for 16 years.Methods A retrospective analysis of the data of patients in single-center vascular surgery in the past 16 years was carried out.The patients with chronic lower limb ischemia caused by lower limb arteriosclerosis obliterans were screened out,and the data of operation information,amputation,length of stay and hospitalization expenses during hospitalization were collected.Results A total of 4 602 patients were included,of whom 57.39% were diabetic.It was found that the number of patients admitted,the number of endovascular treatment,the average cost of hospitalization increased year by year,and the average length of hospitalization decreased year by year.The amputation rate decreased from 8.12% (from 2002 to 2007) to 0.92% (from 2008 to 2017) (P < 0.01).The average days of hospitalization decreased from 28.20 days (from 2002 to 2007) to 11.65 days (from 2008 to 2017) (P < 0.01).The average hospitalization cost rose from 54 466.94 yuan (from 2002 to 2007) to 73 685.22 yuan (from 2008-2017) (P < 0.01).There was no significant difference in amputation rate,hospitalization days and hospitalization costs between diabetic group and non-diabetic group.In diabetic subgroup,amputation rate decreased from 8.83% (between 2002 and 2007) to 1.05% (between 2008 and 2017) (P < 0.01).The average hospitalization days decreased from 30.12 days (between 2002 and 2007) to 12.60 days (between 2008 and 2017) (P < 0.01).The average cost of hospitalization rose from 58 530.94 yuan (between 2002 and 2007) to 74 433.75 yuan (between 2008 and 2017) (P < 0.01).Conclusions From 2002 to 2017,the number of patients with chronic lower limb ischemia increased gradually,and so as the number of endovascular treatment.While the amputation rate and average hospitalization time decreased,and the average hospitalization cost increased.The same trend was observed in the diabetic subgroup.The significant decrease in amputation rate may be related to the development of endovascular therapy and angiogenesis therapy.
		                        		
		                        		
		                        		
		                        	
8.Preliminary study on selective usage of embolic protection device during SilverHawk atherectomy to prevent distal embolization
Lianrui GUO ; Yongquan GU ; Lixing QI ; Shijun CUI ; Yingfeng WU ; Zhu TONG ; Jianming GUO ; Yixia QI ; Shengjia YANG ; Xixiang GAO ; Jian ZHANG ; Zhonggao WANG
Journal of Chinese Physician 2017;19(12):1768-1771
		                        		
		                        			
		                        			Objective To explore the clinical effectiveness and safety of selective usage of embolic protection device to prevent distal embolization during SilverHawk atherectomy for atherosclerotic femoropo-pliteal artery disease. Methods From Jan 2014 to December 2015, 45 femoropopliteal artery atherosclerot-ic patients were treated with SilverHawk atherectomy and selective embolic protection device (EPD). The indication for EPD was instent restenosis, highly calcified lesion, suspicious of thrombosis, ulcerated le-sion, and single below-the-knee runoff. All cases who met the indication were treated with atherectomy and EPD, and those who did not meet the indication were treated with or without EPD according to the patient's choice. The embolic related complications were analyzed. Results Twenty three out of 45 patients who met the EPD indication were all treated with SilverHawk atherectomy under EPD protection, filter captured deb-ris in 17 patients (73. 9%) of the patients. The other 22 patients who did not meet the indication were di-vided into 2 groups according to the patient's choice of EPD usage, 11 were treated by atherectomy with EPD and 11 without EPD. One case out of 11 unindicated patients without EPD suffered a tibioperoneal trunk embolization and restored with catheter aspiration. For 1/11 (9. 1%) unindicated cases with EPD protec-tion, the filter captured embolization. There was a significant difference of distal embolization rate between the indicated and unindicated patients (χ2 =19. 368,P =0. 000). All filters were retrieved successfully without any distal embolization and any complications except arterial spasm occurred in 2 patients and re-stored well with nitroglycerin. Conclusions It is safe and effective for selective usage of embolic protection device to prevent distal embolization during SilverHawk atherectomy for atherosclerotic femoropopliteal artery disease.
		                        		
		                        		
		                        		
		                        	
9.The long-term patency and fracture rates of stents placed in the popliteal arteries in Chinese patients with chronic critical limb ischemia or lifestyle-limiting claudication
Shijun CUI ; Lianrui GUO ; Lixing QI ; Zhu TONG ; Jianming GUO ; Yongquan GU
Journal of Chinese Physician 2017;19(12):1772-1775
		                        		
		                        			
		                        			Objective To evaluate efficacy, safety, and long-term patency and fracture rates of self-expanding nitinol stent after failed percutaneous transluminal angioplasty ( PTA) of popliteal artery in patients with chronic critical limb ischemia ( CLI ) or lifestyle-limiting claudication in Chinese patients. Methods A total of 64 patients (68 limbs) was retrospectively analyzed who underwent endovascular treat-ment for stenoocclusive lesions in the popliteal artery from January 2008 to July 2012. In a single-center study, self-expanding nitinol stents were implanted in 68 popliteal arteries for the treatment of stenosis grea-ter than 75% or occlusions in the popliteal arteries. Follow-up patency was assessed by clinical examina-tion, ankle-brachial index, and color ultrasound or digital subtraction angiography, and stent fracture was assessed by plain X-rays at 6 and 12 months and annually thereafter. Results Stent implantation was suc-cessful in 63 patients (98. 5%). Mean follow-up was 22. 1 months (22. 1 ± 13. 8). 1-year, 2-year and 3-year primary patency rate ( PPR) was 76%, 60% and 43%, respectively. The 1-year, 2-year, and 3-year secondary patency rate ( SPR) was 87%, 82% and 73%, respectively. The 1-year , 2-year, and 3-year PPRs and SPRs for subgroups, trans-articular surface versus no trans-articular surface were not significant difference (P>0. 05). Two patients were lost to follow-up (3%). Two patients (3%) died during the fol-low-up period. Stent fractures were seen in 11 limbs (11 of 68, 16. 2%) and the fractures were identified in P1 and P2 segment. Three patients were performed above-knee amputation because of stent occlusion and gangrene of limb (3 of 68, 4. 4%). Conclusions Stent implantation is a safe and effective treatment of popliteal artery occlusion. One can improve the popliteal arterial stent patency rate by interventional tech-nique, such as transcatheter arterial thrombolysis, balloon angioplasty, silverhawk atherectomy, and rescue stent. One maybe try to avoid stent placement up to the popliteal arterial P1 and P2 segment owing to stent fracture.
		                        		
		                        		
		                        		
		                        	
10.Treatment of atherosclerosis obliterans in lower extremity with drug-coated balloon
Lixing QI ; Yongquan GU ; Lianrui GUO ; Shijun CUI ; Zhu TONG ; Shengjia YANG ; Yixia QI
Journal of Chinese Physician 2017;19(12):1782-1785
		                        		
		                        			
		                        			Objective To investigate the clinical outcome of drug-coated balloon ( DCB) treated atherosclerosis obliterans ( ASO) in lower extremity. Methods Data of 28 patients were retrospectively an-alyzed to determine the effectiveness and characteristics of DCB treatment. Results All the 28 patients were successfully treated with endovascular intervention therapy. Lesions mainly located in the superficial femoral arteries were divided into Groups A, B, C, and D according to TransAtlantic InterSociety Consensus (TASC) Ⅱ classification. Follow-up at 6, 9, and 12 months showed 100%, 84. 6% and 76. 9% patency rate in treated artery. After 9 months of endovascular intervention therapy, the combined artery patency rates in Groups A and B was 92. 8%, which was significantly better than 66. 7% in Groups C and D ( P <0. 05 ) . DCB angioplasty had an artery patency rate of 86. 7%, while DCB angioplasty plus stenting had the patency rate of 85. 7% (P>0. 05). Artery patency rate of Simple DCB angioplasty in ten patients (Exclu-ding patients with in-stent restenosis ) was 80% and of Atherectomy plus DCB angioplasty in 5 patients was 100% (P<0. 05). Conclusions DCB angioplasty has superiority over conventional intervention therapy. Combined debulky and DCB angioplasty appear to be the best choice in current treatment of ASO in lower extremity.
		                        		
		                        		
		                        		
		                        	
            
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