1.Mito-TEMPO Ameliorates Sodium Palmitate Induced Ferroptosis in MIN6 Cells through PINK1/Parkin-Mediated Mitophagy
Chang BAOLEI ; Su YANYU ; Li TINGTING ; Zheng YANXIA ; Yang RUIRUI ; Lu HENG ; Wang HAO ; Ding YUSONG
Biomedical and Environmental Sciences 2024;37(10):1128-1141
		                        		
		                        			
		                        			Objective Mitochondrial reactive oxygen species(mtROS)could cause damage to pancreatic β-cells,rendering them susceptible to oxidative damage.Hence,investigating the potential of the mitochondria-targeted antioxidant(Mito-TEMPO)to protect pancreatic β-cells from ferroptosis by mitigating lipid peroxidation becomes crucial. Methods MIN6 cells were cultured in vitro with 100 μmol/L sodium palmitate(SP)to simulate diabetes.FerroOrange was utilized for the detection of Fe2+fluorescence staining,BODIPY581/591C11 for lipid reactive oxygen species,and MitoSox-Red for mtROS.Alterations in mitophagy levels were assessed through the co-localization of lysosomal and mitochondrial fluorescence.Western blotting was employed to quantify protein levels of Acsl4,GPX4,FSP1,FE,PINK1,Parkin,TOMM20,P62,and LC3.Subsequently,interventions were implemented using Mito-TEMPO and Carbonyl cyanide 3-chlorophenylhydrazone(CCCP)to observe changes in ferroptosis and mitophagy within MIN6 cells. Results We found that SP induced a dose-dependent increase in Fe2+and lipid ROS in MIN6 cells while decreasing the expression levels of GPX4 and FSP1 proteins.Through bioinformatics analysis,it has been uncovered that mitophagy assumes a crucial role within the ferroptosis pathway associated with diabetes.Additionally,SP decreased the expression of mitophagy-related proteins PINK1 and Parkin,leading to mtROS overproduction.Conversely,Mito-TEMPO effectively eliminated mtROS while activating the mitophagy pathways involving PINK1 and Parkin,thereby reducing the occurrence of ferroptosis in MIN6 cells.CCCP also demonstrated efficacy in reducing ferroptosis in MIN6 cells. Conclusion In summary,Mito-TEMPO proved effective in attenuating mtROS production and initiating mitophagy pathways mediated by PINK1 and Parkin in MIN6 cells.Consequently,this decreased iron overload and lipid peroxidation,ultimately safeguarding the cells from ferroptosis.
		                        		
		                        		
		                        		
		                        	
2.Use of indocyanine green fluorescence navigation in laparoscopic anatomical hepatectomy.
Zi Qi HOU ; Qing Yun XIE ; Ming Heng LIAO ; Chang LIU ; Guo Teng QIU ; Zhao Xing JIN ; Shi Zheng MI ; Ji Wei HUANG
Chinese Journal of Surgery 2023;61(5):368-374
		                        		
		                        			
		                        			Objective: To examine the clinical value of fluorescence-guided indocyanine green (ICG) laparoscopic anatomical hepatectomy in the treatment of primary hepatocellular carcinoma. Methods: Data from patients diagnosed with hepatocellular carcinoma and who underwent laparoscopic hepatectomy with ICG fluorescence navigation in the Department of Liver Surgery and Liver Transplantation Center of West China Hospital between September 2020 and May 2022 were retrospectively collected. There were 53 males and 19 females, with an age of (55.5±12.9)years(range:42.6 to 68.4 years). Among them, 13 of the cases underwent laparoscopic anatomical liver resection(LALR) guided by tans-arterial ICG,43 of the cases received LAIR guided by portal vein negative ICG, and 16 of the cases received LALR positive by portal vein. Comparison among the three groups was performed by one-way ANOVA; and the rank sum test was used for comparison between groups. The counting data was expressed as percentage,and the χ2 test or Fisher's exact probability method was used for comparison between groups. Results: (1) Postoperative pathology: Resection R0 was achieved in all operations. The maximum tumor diameter of the patients in the arterial staining group, the reverse staining group, and the positive staining group(M (IQR)) was 2.5 (2.4) cm, 3.0 (2.5) cm and 3.0(2.4) cm,respectively. There were no statistically significant differences in the maximum tumor diameter between the three groups (P=0.364). The minimum tumor margin was 1.1 (1.1) cm, 1.0 (1.0) cm, 1.1 (1.6) cm in the the arterial staining group, reverse staining group and the positive staining group, respectively. There was no significant difference in the margin among the three groups (P=0.878). (2) Operation conditions: the operation time of the arterial staining group, the negative staining group, and the positive portal staining group was (348±93)minutes,(277±112)minutes,and (295±116)minutes,respectively. There were no significant differences in operation time among the three groups (P=0.134). The intraoperative blood loss of the three groups was 80(150)ml,200(350)ml,and 100(150)ml,respectively. There was no statistically significant difference in intraoperative bleeding volume between the three groups(P=0.743). All cases were not transfused during the operation and were not converted to laparotomy. ALT in the arterial staining group was higher than in the negative staining group in the first two days after the operation ((559±398)IU/L307(257) IU/L, q=235.5,P=0.004;(611±389)IU/L(331±242) IU/L, q=265.2, P=0.002). There was only one case of a grade III complication (Clavien-Dindo grading system) postoperative complication in the negative and positive staining group of the portal vein, respectively. Tumor markers in all patients decreased to the normal range after 2 months of operation. Conclusion: Laparoscopic anatomical hepatectomy guided by ICG fluorescence through arterial staining and portal vein staining is safe and feasible for primary hepatocellular carcinoma treatment.
		                        		
		                        		
		                        		
		                        	
3.Mis-estimation of coronary lesions and rectification by SYNTAX score feedback for coronary revascularization appropriateness.
Shen LIN ; Heng ZHANG ; Si-Peng CHEN ; Chen-Fei RAO ; Fan WU ; Fa-Jun ZHOU ; Yun WANG ; Hong-Bing YAN ; Ke-Fei DOU ; Yong-Jian WU ; Yi-Da TANG ; Li-Hua XIE ; Chang-Dong GUAN ; Bo XU ; Zhe ZHENG
Chinese Medical Journal 2020;133(11):1276-1284
		                        		
		                        			BACKGROUND:
		                        			Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate revascularization. Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is a comprehensive system to evaluate the complexity of the overall lesions. We hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease (CAD).
		                        		
		                        			METHODS:
		                        			In this single-center, historical control study, patients with stable CAD with coronary lesion stenosis ≥50% were consecutively recruited. During the control period, SYNTAX scores were calculated by treating cardiologists. During the intervention period, SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid decision-making. The primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary revascularization.
		                        		
		                        			RESULTS:
		                        			A total of 3245 patients were enrolled and assigned to the control group (08/2016-03/2017, n = 1525) or the intervention group (03/2017-09/2017, n = 1720). For SYNTAX score tertiles, 17.9% patients were overestimated and 4.3% were underestimated by cardiologists in the control group. After adjustment, inappropriate revascularization significantly decreased in the intervention group compared with the control group (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.73-0.95; P = 0.007). Both inappropriate percutaneous coronary intervention (adjusted OR: 0.82; 95% CI: 0.74-0.92; P < 0.001) and percutaneous coronary intervention utilization (adjusted OR: 0.88; 95% CI: 0.79-0.98; P = 0.016) decreased significantly in the intervention group. There was no significant difference in 1-year adverse cardiac events between the control group and the intervention group.
		                        		
		                        			CONCLUSIONS:
		                        			Real-time SYNTAX score feedback significantly reduced inappropriate coronary revascularization in stable patients with CAD.
		                        		
		                        			CLINICAL TRIAL REGISTRATION
		                        			Nos. NCT03068858 and NCT02880605; https://www.clinicaltrials.gov.
		                        		
		                        		
		                        		
		                        	
5.Repeatability of macular thickness profiles of intra-retinal layers determined by an automated algorithm with Cirrus HD-OCT
Sheng, YANG ; Chang-Zheng, CHEN ; Jing-Heng, LIU
International Eye Science 2017;17(8):1558-1561
		                        		
		                        			
		                        			AIM: To evaluate the repeatability and reproducibility of thickness profile measurement of intra-retinal layers determined by an automated algorithm applied to OCT images from Cirrus optical coherence tomography (OCT) instrument.METHODS: In this prospective cross-sectional study,retinal thickness images at 6mm×6mm around fovea were obtained from 86 eyes of 43 normal subjects with Cirrus HD-OCT instrument.The retinal images from patients were analysis by Cirrus automated algorithm GCA software,including ganglion cell layer and inner plexiform layer(GCIPL).During this study,operator A would make 2 times measurements to all patients,after that operator B would make another 2 times measurements by Repeat scan model.All the data,including GCL average thickness,min thickness,12 clock average thickness,2 clock average thickness,4 clock average thickness,6 clock average thickness,8 clock average thickness and 10 clock average thickness were measured by SPSS 15.0 software.Standard deviation (SD),coefficient of variation (CV) and interclass correlation coefficient (ICC) were calculated from the results of three-times tests by different examiner to evaluate the repeatability and from the results of two different examiners to assess the reproducibility.Written informed consent was obtained from each subject prior to any medical procedure.RESULTS: The average GCIPL thickness of OD was 85.12±3.95μm;the minimum average GCIPL thickness was 83.21±4.41μm;the standard deviation of OD in clock map was from 3.79μm to 4.84μm;CV(95%CI) was between 0.26 and 0.93;ICC was from 0.939 to 0.989.The average GCL+IPL thickness of OS was 84.65±8.73μm;the minimum average GCPL thickness was 81±13.08μm;the standard deviation of OS in clock map was from 8.24μm to 10.56μm;CV(95%CI) was between 0.92 and 4.94;ICC was from 0.264 to 0.968.CONCLUSION: Cirrus HD-OCT GCA software with automated algorithm can offer accurate and repeatable thickness profile of OCT retinal image.GCA is a useful and reliable approach to the measurement of intra-retinal layer thickness,which may improve the diagnosis and monitoring of retinal diseases.
		                        		
		                        		
		                        		
		                        	
6.Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based on PK/PD.
Shi-jia LIU ; Guo-liang DAI ; Bing-ting SUN ; Chang-yin LI ; Lei WU ; Ma SHI-TANG ; Wen-zheng JU ; Heng-shan TAN ; Hai-yan FU
China Journal of Chinese Materia Medica 2015;40(2):334-338
		                        		
		                        			
		                        			To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Arthritis, Rheumatoid
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Biomarkers
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Interleukin-17
		                        			;
		                        		
		                        			antagonists & inhibitors
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Interleukin-6
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Phytotherapy
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Tripterygium
		                        			;
		                        		
		                        			Triterpenes
		                        			;
		                        		
		                        			pharmacokinetics
		                        			;
		                        		
		                        			pharmacology
		                        			
		                        		
		                        	
7.Leihong granule intervened in-stent restenosis after endovascular therapy for lower extremity arterial occlusive diseases: a clinical observation.
Bing HAN ; Chang-Qing GE ; Li-Pu WANG ; Su-Fei ZHANG ; Heng-Zhou LI ; Hong-Guang ZHANG ; Chen-Guang ZHOU ; Guo-Hui JI ; Zheng YANG ; Liang ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(2):153-156
OBJECTIVETo observe the intervention effect of Leihong Granule (LG) in in-stent restenosis (ISR) after endovascular therapy for lower extremity arterial occlusive diseases (LEAOD).
METHODSRecruited 80 LEAOD patients who successfully underwent endovascular therapy (balloon dilation and stent implantation) were randomly assigned to two groups, the control group and the LG group, 40 in each group. Patients in the control group received basic treatment, while those in the LG group additionally took LG for 3 months. Plasma levels of IL-10, IL-18, CRP, and the intima-media thickness (IMT) of lower extremity artery were observed in the two groups between and after treatment. The rate of stent patency, ABI, intermittent claudication, rest pain, and the incidence of amputation the two groups were recorded and observed in the two groups.
RESULTSIn the control group, serum levels of IL-10, IL-18, CRP, and IMT were significantly higher one month after surgery than before surgery (P < 0.05). There was no significant difference in serum levels of IL-10, IL-18, CRP, or IMT between the two groups before surgery (P > 0.05). These indices were obviously lower in the LG group than in the control group after surgery (P < 0.05). Compared with the control group, the incidence rates of intermittent claudication and the rest pain at 6 months and 12 months after surgery significantly decreased (P < 0.05). The stent patency rate at 6 months and 12 months after surgery, and ABI were significantly higher than those of the control group (P < 0.05). There was no statistical difference in the amputation rate between the two groups (P > 0.05).
CONCLUSIONLG might effectively improve ischemic symptoms of affected limbs possibly through lowering the ISR rate after endovascular therapy for LEAOD through preventing immunosuppressive actions.
Aged ; Aged, 80 and over ; Arterial Occlusive Diseases ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Graft Occlusion, Vascular ; therapy ; Humans ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Phytotherapy ; Stents ; Treatment Outcome
8.Efficacy of surgical therapy for carotid body tumors.
Lian LI-SHAN ; Liu CHANG-WEI ; Guan HENG ; Zheng YUE-HONG ; Chen XING-MING ; Li YONG-JUN
Chinese Medical Sciences Journal 2011;26(4):241-245
OBJECTIVETo evaluate the efficacy of surgical therapy for carotid body tumors.
METHODSA retrospective analysis was conducted, covering the diagnosis, surgical procedure, postoperative complications, and prognosis of 120 cases of carotid body tumors in Peking Union Medical College Hospital from 1949 to May, 2011.
RESULTSSurgical excision was successfully performed in 111 cases with 117 tumors. In all those cases, 50 underwent simple tumor resection, 42 underwent resection of tumors and ligation of the external carotid arteries, 7 underwent co-resection of tumors and common carotid arteries, internal carotid arteries, as well as external arteries without vascular reconstruction, and the other 12 cases experienced tumor resection and vascular reconstruction as internal carotid arteries were involved. After operation, 3 cases developed cerebral infarction, 30 cases showed cranial nerve palsy, including 15 cases of hypoglossal nerve damage, 10 cases of vagus paralysis, and 5 cases of Horner's syndrome.
CONCLUSIONIt is essential to make a proper surgical strategy, which can reduce postoperative complications.
Adolescent ; Adult ; Aged ; Carotid Body Tumor ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Retrospective Studies
9.Endovascular revascularization for lower extremity atherosclerosis obliterans in elderly patients:a report of 86 cases.
Wei YE ; Chang-wei LIU ; Yong-jun LI ; Yue-hong ZHENG ; Ji-dong WU ; Bao LIU ; Rong ZENG ; Wei-wei WU ; Xiao-jun SONG ; Heng GUAN
Chinese Journal of Surgery 2010;48(4):261-264
OBJECTIVETo analyze the outcome and risk factors of endovascular revascularization of lower limb artery for elder patients.
METHODSFrom January 2006 to November 2008, 86 elder patients (98 ischemia limbs) underwent endovascular revascularization due to lower limb ischemia. Age of this group were 60 to 82 years old with a mean of (70 +/- 6) years old. Fifty-four limbs (55.0%) had severe intermittent claudication, 28 limbs (28.6%) had rest pain, 11 limbs (11.2%) had ulcer, and 5 limbs (5.1%) had gangrene. Sixty-six limbs were mono segment disease, including 25 aorta-iliac lesions, 33 femoral-popliteal lesions and 8 infra-popliteal lesions. Thirty-two limbs were multiple segment disease involving 2 or 3 segment lesions. Mortality, morbidity, primary patency, secondary patency and limb salvage were retrospectively analyzed. Risk factors on outcome were also evaluated.
RESULTSTen limbs underwent angioplasty, while the rest 88 limbs underwent angioplasty plus primary stent implantation. The total operation success rate was 95.9%. Perioperative mortality within the first 30 d was 0. Perioperative morbidity within the first 30 d was 5 cases (5.1%), including 2 myocardial infarction, 2 major amputations and 1 irreversible contrast-induced nephropathy. Follow-up duration were 1 to 35 months with a mean of (18 +/- 10) months. Eighty-three (96.5%) patients had effectively follow-up. Mortality was 2.3% (2 cases died due to myocardial infarction). Primary patency rate was 83.7%, secondary patency rate was 94.9% and limb salvage rate was 95.9%. Risk factor analysis showed that diabetes mellitus, critical ischemia and multiple segment lesions were associated with worse patency.
CONCLUSIONSEndovascular treatment is effective, safe and repeatable revascularization for elder patients of Critical lower limb ischemia. Patients with diabetes mellitus, critical ischemia and multiple segment lesions should be paid more attention because their rather worse outcome.
Aged ; Aged, 80 and over ; Angioplasty, Balloon ; Arteriosclerosis Obliterans ; surgery ; Female ; Follow-Up Studies ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; Stents ; Treatment Outcome
            
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