1.Prospective study of lung V5 and V10 in predicting radiation-induced lung injury in advanced non-small-cell lung cancer treated with three-dimensional conformal radiation therapy
Heyi FU ; Bing LU ; Bingqing XU ; Yinxiang HU ; Jiaying GAN ; Weiwei OUYANG ; Shengfa SU ; Gang WANG ; Huiqin LI
Chinese Journal of Radiation Oncology 2009;18(6):439-442
Objective To analyze the low dose-volume associated with radiation-induced lung injury (RILI) in patients with advanced non-small cell lung cancer (NSCLC) treated by three-dimensional confor-real radiation therapy (3DCRT). Methods Data of 100 patients with histologically proved NSCLC treated with 3DCRT or IMRT between November 2006 and January 2009 were collected. Nine patients treated with radiotherapy alone and 91 with radiotherapy combined with chemotherapy. A median dose of 70 Gy (range,60-80 Gy) was delivered with late-course accelerated hyperfractionated radiotherapy (LAHRT). Twenty-four patients received dose of 61-69 Gy and 76 received more than 70 Gy. The V_5 ,V_(10) ,V_(20) ,V_(30)and mean lung dose (MLD) were calculated from the dose volume histogram system. The RILI was evaluated according to Common Toxicity Criteria 3.0(CTC 3.0). Results The range of V_5 ,V_(10) ,V_(20) ,V_(30) was 37%-98%,27%-78%, 17%-54% and 9%-31%, respectively, with a median value of 65%, 47.5%, 31% and 24%, respectively. The acute RILI of grade 1, 2, 3, 4 and 5 was observed in 34, 27, 8, 1 and 1 patients,respectively. The chronic RILI of grade 1, 2 and 3 was observed in 46, 14 and 2 patients, respectively. V_5 ,V_(10) ,V_(20) and MLD were significantly correlated with acute RILI of ≥ grade 1. V_5 ,V_(20) ,V_(30) and MLD were significantly correlated with acute RILI of ≥ grade 2. The acute RILI of ≥ grade 2 was significantly in-creased when V_5, V_(20) and V_(30) were more than 65%, 31% and 24%, respectively. The acute RILI of ≥ grade 3 was significantly increased when V_5 was more than 65%. The acute RILI of ≥ grade 1 was signifi-candy increased when V_(20)was more than 31%. The gross tumor volume and planning target volume were sig-nificantly correlated with the acute RILI of ≥ grade 1 and chronic RILI of ≥ grade 2. Conclusions The dose-volume V_5 and V_(10) are effective in predicting RILI.
2.Role of active screening in the diagnosis and treatment of early lung cancer and suggestions for health management
Zeng XIONG ; Bingqing LONG ; Shaohui LIU ; Shulin LIU ; Yuanda CHENG ; Bihan OUYANG ; Baoxiang WANG ; Xuewei ZHANG ; Weihua LIAO
Chinese Journal of Health Management 2023;17(3):188-193
Objective:To explore the role of active screening in the diagnosis and treatment of early lung cancer, and give health management recommendations.Methods:A retrospective study was conducted to collect lung cancer patients who had complete population sociology, clinical information, pathology and imaging characteristics in the Thoracic Surgery in Xiangya Hospital of Central South University from 2016 to 2019. According to different diagnostic modes, they were divided into an active screening group (1082 cases) and a passive case finding group (974 cases), to analyze their differences in demographic sociological, clinical information, pathology and imaging characteristics, and to discuss the key points of population management in the active screening group.Results:From 2016 to 2019, the proportion of lung cancer patients in the active screening group increased from 36.1% to 54.2%, and the proportion of patients found to have lung cancer by CT examination in the active screening group increased from 82.2% to 96.8%. Compared with the passive case finding group, the active screening group had a higher proportion of women, non-smokers, patients with precursor glandular lesions and adenocarcinoma, patients in stage 0 and stage I, patients with lesion diameter (d)≤1 cm and 1
3.Mechanistic study of anti-inflammatory effect of Fu-Fang-Yu-Jie granules through inhibition of NLRP3 inflammasome activation in BMDM
Yuhui MA ; Jialei MENG ; Lin YUAN ; Luyao QI ; Bingqing OUYANG ; Ming LEI
Chinese Journal of Immunology 2024;40(7):1467-1473
Objective:To investigate the effect of Fu-Fang-Yu-Jie(FFYJ)granules on LPS-induced inflammation model in bone marrow-derived macrophages(BMDM)and its intervention of FFYJ on nucleotide-bound oligomeric domain-like receptor protein 3(NLRP3)inflammatory signaling pathway in macrophages.Methods:Primary cells were extracted and isolated from the leg bone mar-row of C57BL/6 mice and BMDM macrophages were obtained after 7 days of induction with 50 ng/ml M-CSF.Groups included control group(Control),model group(LPS+ATP),FFYJ low dose group(FFYJ 50 μg/ml),FFYJ medium dose group(FFYJ 100 μg/ml),FFYJ high dose group(FFYJ 200 μg/ml)and positive drug dexamethasone group(DEX).BMDM in FFYJ treatment group and posi-tive drug group were pretreated for 1 hour before modeling.Lactate dehydrogenase(LDH)release assay was used to detect the level of LDH in the supernatant of each group of cells;ELISA was used to detect the level of inflammatory factors TNF-α,IL-6 and IL-1β in the supernatant of each group of cells;qRT-PCR was used to detect the levels of TNF-α,IL-6 and IL-1β in each group of cells;protein levels of NF-κB,p-NF-κB,NLRP3,Caspase-1 p45,Caspase-1 p20 and GSDMD-N in each group of cells were detected by Western blot;inverted fluorescence microscope was used to observe the cell pyroptosis of each group after Hoechst-PI staining.Results:Compared with control group,the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of the model group were signifi-cantly higher(P<0.000 1);the mRNA levels of TNF-α,IL-6 and IL-1β in the model group were significantly higher(P<0.000 1);the protein levels of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N were significantly higher(P<0.05);and the number of PI-posi-tive cells was significantly higher(P<0.05).Compared with the model group,FFYJ and DEX significantly reduced the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of BMDMs(P<0.05);down-regulated the mRNA levels of TNF-α,IL-6 and IL-1β in the cells(P<0.05);and inhibited the expressions of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N protein expressions(P<0.05);and significantly reduced the number of PI-positive cells(P<0.05).Conclusion:FFYJ exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in BMDM macrophages.
4.The mechanism of 5-hydroxytryptamine in electroacupuncture pre-treatment for myocardial injury in sepsis mice
Yunfeng LI ; Luyao QI ; Bingqing OUYANG ; Huan GENG ; Xiaoxiao LI ; Ming LEI
Chinese Critical Care Medicine 2024;36(8):835-840
Objective:To observe the changes of 5-hydroxytryptamine (5-HT) level in myocardial tissue of pre-treatment mice with sepsis myocardial injury by electroacupuncture at Zusanli point, and to explore the protective effect and possible mechanism of electroacupuncture on myocardial injury in sepsis.Methods:Twenty male C57BL/6 mice were divided into control group (NC group), sepsis model group (LPS group), electroacupuncture group (EA group) and electroacupuncture + fluoxetine group (EA+FLU group) by random number table method, with 5 mice in each group. The myocardial injury model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 g/L. The NC group was intraperitoneally injected with the same amount of normal saline. 3 days before mold making, EA group and EA+FLU group were electrocuted at Zusanli point on both sides for 15 minutes, once a day for 3 days. The EA+FLU group was intraperitoneally injected fluoxetine 1.4 g/L before electroacupuncture. After modeling, the cardiac histopathological changes were observed by hematoxylin-eosin (HE) staining. The serum levels of inflammatory cytokines interleukins (IL-6, IL-8), and tumor necrosis factor-α (TNF-α), the content of 5-HT in myocardial tissue, myocardial injury markers MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTnI), and the levels of adenosine triphosphate (ATP) and lactic acid in myocardial tissue were detected. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expressions of 5-hydroxytryptamine transporter (5-HTT), hexokinase 2 (HK2) and glucose transporter 4 (GLUT4) in myocardial tissue. GLUT4 expression in myocardial tissue was detected by immunofluorescence assay.Results:Compared with NC group, the serum levels of IL-6, IL-1β and TNF-α, myocardial 5-HT content, myocardial tissue injury markers CK-MB, cTnI in LPS group and EA+FLU group were significantly increased. Compared with LPS group, the above indexes in EA group were significantly decreased [IL-6 (ng/L): 443.03±156.16 vs. 19?843.75±0.00, IL-1β (ng/L): 75.72±10.60 vs. 894.66±350.88, TNF-α (ng/L): 46.17±4.71 vs. 533.01±170.58, 5-HT (μg/L): 161.19±5.96 vs. 244.74±14.38, CK-MB (ng/L): 468.21±12.46 vs. 662.02±22.54, cTnI (ng/L): 0.83±0.05 vs. 0.99±0.08, all P < 0.05]. Compared with NC group, the levels of ATP in myocardium of LPS group, EA group and EA+FLU group were significantly decreased, the levels of lactic acid in myocardium were significantly increased. Compared with LPS group, the level of ATP in myocardium of EA group was significantly increased, the level of lactic acid in myocardium was significantly decreased [ATP (mmol/L): 0.10±0.01 vs. 0.08±0.01, lactic acid (mmol/L): 56.03±1.07 vs. 72.45±4.32, both P < 0.05]. Compared with NC group, the mRNA expression of HK2 in myocardium of LPS group was significantly increased, and the mRNA expressions of GLUT4 and 5-HTT were significantly decreased. Compared with LPS group, the mRNA expression of HK2 in myocardium of EA group was significantly decreased, the mRNA expressions of GLUT4 and 5-HTT were significantly increased [HK2 mRNA (relative expression level): 0.73±0.19 vs. 1.82±0.57, GLUT4 mRNA (relative expression level): 1.00±0.33 vs. 0.47±0.18, 5-HTT mRNA (relative expression level): 1.18±0.31 vs. 0.38±0.15, all P < 0.05]. Compared with NC group, the fluorescence intensity of GLUT4 in LPS group and EA+FLU group were significantly decreased. Compared with LPS group, the fluorescence intensity of GLUT4 in EA group was significantly enhanced. Conclusions:Electroacupunctureat Zusanli can reduce the content of 5-HT in myocardial tissue of sepsis mice, and its regulatory mechanism may be related to the regulation of 5-HTT and GLUT4.
5.Role of Mitophagy Affecting Macrophage Polarization in Immunomodulationin Sepsis and Traditional Chinese Medicine Intervention:A Review
Luyao QI ; Jixiang XING ; Bingqing OUYANG ; Yunfeng LI ; Ming LEI
Acta Academiae Medicinae Sinicae 2024;46(5):720-731
Sepsis,a syndrome characterized by organ dysfunction caused by infection,exhibits high incidence and mortality.The pathogenesis of sepsis is complex and involves a cascade of immune reactions,with no specific drugs currently available.Sepsis is mainly treated with Western medical supportive therapies such as antibiotics,hemodynamic management,and mechanical ventilation.However,the occurrence of immune cas-cades significantly increases patients'vulnerability to secondary infections,leading to septic shock and unfavor-able prognoses.International consensus indicates that initiating dynamic monitoring of patients'immune function within 48 h post-sepsis diagnosis can effectively decelerate sepsis progression.Extensive studies have indicated that macrophages,serving as the first line of defense in the innate immune system against pathogens,play a vital role in treating immune system disorders by regulating macrophage polarization and the ratio of cytokines activated.Mitophagy,a hot topic in recent years,has increasingly been shown to play a crucial role in regulating inflammatory signal transduction.Promoting mitophagy during the stage of cytokine storm can mitigate uncontrolled infection and excessive inflammation in sepsis,and inhibiting mitophagy during immunosuppression can enhance host immunity,facilitate bacterial clearance,and improve the survival rate of patients.The idea of treating dis-ease before its onset in traditional Chinese medicine(TCM)coincides with the current consensus among sepsis experts on prevention and interception.The TCM therapies such as extracts of Chinese medicine decoction pieces,TCM compound prescriptions,and acupuncture and moxibustion have the effects of clearing heat and detoxifying,activating blood and resolving stasis,reinforcing healthy qi and consolidating root,and purging.These approa-ches dynamically regulate the levels of mitophagy-related proteins,such as phosphatase and tension homology-induced putative kinase 1,Parkin-E3 ubiquitin protein ligase,light chain 3,and p62,while maintaining a suitable ratio between M1 and M2 macrophages.Consequently,they effectively prevent,halt,or even reverse the progression of sepsis,offering a novel perspective on sepsis management by emphasizing prevention before disease onset and controlling development of existing disease.