1.Hypertonic saline resuscitation contributes to early accumulation of circulating myeloid-derived suppressor cells in a rat model of hemorrhagic shock
Yuan-Qiang LU ; Lin-Hui GU ; Qin ZHANG ; Jiu-Kun JIANG ; Han-Zhou MOU
Chinese Medical Journal 2013;(7):1317-1322
Background Hemorrhagic shock is usually associated with complicated immune and inflammatory responses,which are sometimes crucial for the prognosis.As regulators of the immune and inflammatory system; proliferation,migration,distribution and activation of myeloid-derived suppressor cells (MDSCs) are intimately linked to the inflammation cascade.Methods In a model of severe hemorrhagic shock,thirty-five rats were randomly divided into control,sham,normal saline resuscitation (NS),hypertonic saline resuscitation (HTS),and hydroxyethyl starch resuscitation (HES),with seven in each group.M DSCs were analyzed by flow cytometric staining of CD11b/c+Gra+ in peripheral blood mononuclear cells (PBMC),spleen cell suspensions,and bone marrow nucleated cells (BMNC).Simultaneously,the expressions of arginase-1 (ARG-1) and inducible nitric oxide synthase (iNOS) mRNA in MDSCs were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results In the early stage after hemorrhagic shock,fluid resuscitation and emergency treatment,the MDSCs in the PBMC of NS,HTS and HES groups markedly increased,and MDSCs in BMNC of these groups decreased accordingly,significantly different to the control group.In hemorrhagic shock rats infused with HTS at the early resuscitation stage,MDSCs in PBMC increased about 2 and 4 folds,and MDSCs in BMNC decreased about 1.3 and 1.6 folds,as compared to the sham group respectively,with statistically significant difference.Furthermore,compared to the NS and HES groups,the MDSCs in PBMC of HTS group increased 1.6 and 1.8 folds with statistically significant differences; the MDSCs decrease in BMNC was not significant.However,there was no statistically significant difference in MDSCs of spleen among the five groups.In addition,compared to the control,sham,NS and HES groups,the ARG-1 and iNOS mRNA of MDSCs in PBMC,spleen and BMNC in the HTS group had the highest level of expression,but no statistically significant differences were noted.Conclusions In this model of rat with severe and controlled hemorrhagic shock,small volume resuscitation with HTS contributes to dramatically early migration and redistribution of MDSCs from bone marrow to peripheral circulation,compared to resuscitation with NS or HES.
2.Early changes of CD4⁺CD25⁺Foxp3⁺ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation.
Qin ZHANG ; Yuan-Qiang LU ; Jiu-Kun JIANG ; Lin-Hui GU ; Han-Zhou MOU
Chinese Medical Journal 2012;125(12):2163-2167
BACKGROUNDHemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses. This study was conducted to investigate the early pathophysiological changes of CD4(+)CD25(+)Foxp3(+) Treg and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation.
METHODSA rat model of controlled hemorrhagic shock with no fluid resuscitation was established. Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation. Three color flow cytometry was used to detect Tregs, Th1, Th2, Tc1 and Tc2 cells in the samples.
RESULTSIn the peripheral blood of rats, the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P = 0.001). The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08 ± 8.98)% to (23.91 ± 15.36)%, and from (40.40 ± 21.56)% to (65.48 ± 23.88)%, respectively.
CONCLUSIONSAt an early stage, the advent of hemorrhagic shock is related to an early decrease of Tregs, and a mild shift in the Th1/Th2, Tc1/Tc2 balance toward Th1 and Tc1 dominance. These changes are part of a hyper-inflammatory state of the host, and will deteriorate the maintenance of immune balance. Further influences and detailed mechanisms need to be investigated.
Animals ; CD4 Antigens ; metabolism ; Forkhead Transcription Factors ; metabolism ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Resuscitation ; Shock, Hemorrhagic ; immunology ; metabolism ; T-Lymphocytes, Cytotoxic ; metabolism ; T-Lymphocytes, Regulatory ; metabolism ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism
3.Effect of hypertonic versus isotonic saline resuscitation on heme oxygenase-1 expression in visceral organs following hemorrhagic shock in rats.
Yuan Qiang LU ; Lin Hui GU ; Jiu Kun JIANG ; Han Zhou MOU
Biomedical and Environmental Sciences 2013;26(8):684-688
To compare the early effects of hypertonic and isotonic saline resuscitation on heme oxygenase-1 (HO-1) expression in organs of rats with hemorrhagic shock. Rats were randomly divided into hypertonic saline resuscitation (HTS), normal saline resuscitation (NS) and sham groups. HO-1 mRNA, protein expression and apoptosis were evaluated in organs. In the HTS group, significant difference was noted in HO-1 protein in small intestinal mucosa and liver compared with the NS and sham groups, and in HO-1 mRNA in liver and kidney compared with the sham group. The apoptosis of small intestinal mucosa, liver, heart, and lung was significantly lower in the HTS group than that in the NS group. In this study, small volume resuscitation with HTS can efficiently up-regulate the expression level of HO-1 in small intestinal mucosa and liver, which may be one of the mechanisms alleviating organ damage.
Animals
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Base Sequence
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Blood Pressure
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DNA Primers
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Gene Expression Regulation, Enzymologic
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drug effects
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Heme Oxygenase-1
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metabolism
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Intestine, Small
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enzymology
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Kidney
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enzymology
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Liver
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enzymology
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RNA, Messenger
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genetics
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Rats
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Resuscitation
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methods
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Reverse Transcriptase Polymerase Chain Reaction
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Saline Solution, Hypertonic
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pharmacology
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Shock, Hemorrhagic
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enzymology
4.Synovial chondromatosis in the temporomandibular joint: analysis of 5 cases.
Bo JIA ; Hong-Xing CHU ; Jiu-Song HAN ; Xiang SUN ; Zhi-Ping WANG ; Hui-Xi ZHOU
Journal of Southern Medical University 2017;37(6):858-inside back cover
Five patients with synovial chondromatosis in the temporomandibular joint were treated in our hospital between August, 2011 and August, 2014. All the patients underwent preoperative imaging examinations for clinical diagnosis and determining the involvement of the lesions. Surgeries were performed and the lesions were confirmed as synovial chondromatosis by pathological diagnosis. The clinical manifestations, imaging features, diagnosis and treatment results were analyzed. All the 5 patients had pain in the joint region, 3 had limited mouth opening, and 3 had swelling in the joint region. X-ray film showed widening of the joint space in all the 5 cases and radiographic findings showed space-occupying lesions in the intra-articular space. Open joint surgeries was performed and completed successfully in all the cases. The postoperative imaging showed no residual lesions in the surgical area. As a rare clinical entity, synovial chondromatosis in the temporomandibular joint was poorly documented without specific clinical manifestations. The diagnosis of synovial chondromatosis relies on imaging, arthroscopic and pathological findings. Corpus liberum is an important feature of the disease occurring frequently in the joint cavity. Surgical intervention is the primary choice for treatment of synovial chondromatosis in the temporomandibular joint, in which the corpus liberum and the affected synovial membrane shall be removed after joint incision.
5.Hypertonic saline resuscitation contributes to early accumulation of circulating myeloid-derived suppressor cells in a rat model of hemorrhagic shock.
Yuan-Qiang LU ; Lin-Hui GU ; Qin ZHANG ; Jiu-Kun JIANG ; Han-Zhou MOU
Chinese Medical Journal 2013;126(7):1317-1322
BACKGROUNDHemorrhagic shock is usually associated with complicated immune and inflammatory responses, which are sometimes crucial for the prognosis. As regulators of the immune and inflammatory system; proliferation, migration, distribution and activation of myeloid-derived suppressor cells (MDSCs) are intimately linked to the inflammation cascade.
METHODSIn a model of severe hemorrhagic shock, thirty-five rats were randomly divided into control, sham, normal saline resuscitation (NS), hypertonic saline resuscitation (HTS), and hydroxyethyl starch resuscitation (HES), with seven in each group. MDSCs were analyzed by flow cytometric staining of CD11b/c(+)Gra(+) in peripheral blood mononuclear cells (PBMC), spleen cell suspensions, and bone marrow nucleated cells (BMNC). Simultaneously, the expressions of arginase-1 (ARG-1) and inducible nitric oxide synthase (iNOS) mRNA in MDSCs were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
RESULTSIn the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the MDSCs in the PBMC of NS, HTS and HES groups markedly increased, and MDSCs in BMNC of these groups decreased accordingly, significantly different to the control group. In hemorrhagic shock rats infused with HTS at the early resuscitation stage, MDSCs in PBMC increased about 2 and 4 folds, and MDSCs in BMNC decreased about 1.3 and 1.6 folds, as compared to the sham group respectively, with statistically significant difference. Furthermore, compared to the NS and HES groups, the MDSCs in PBMC of HTS group increased 1.6 and 1.8 folds with statistically significant differences; the MDSCs decrease in BMNC was not significant. However, there was no statistically significant difference in MDSCs of spleen among the five groups. In addition, compared to the control, sham, NS and HES groups, the ARG-1 and iNOS mRNA of MDSCs in PBMC, spleen and BMNC in the HTS group had the highest level of expression, but no statistically significant differences were noted.
CONCLUSIONSIn this model of rat with severe and controlled hemorrhagic shock, small volume resuscitation with HTS contributes to dramatically early migration and redistribution of MDSCs from bone marrow to peripheral circulation, compared to resuscitation with NS or HES.
Animals ; Arginase ; genetics ; metabolism ; Blood Pressure ; physiology ; Disease Models, Animal ; Flow Cytometry ; Fluid Therapy ; methods ; Leukocytes, Mononuclear ; metabolism ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Saline Solution, Hypertonic ; therapeutic use ; Shock, Hemorrhagic ; immunology ; metabolism ; therapy
6.In-vivo and ex-vivo studies on region-specific remodeling of large elastic arteries due to simulated weightlessness and its prevention by gravity-based countermeasure.
Fang GAO ; Jiu-Hua CHENG ; Jun-Hui XUE ; Yun-Gang BAI ; Ming-Sheng CHEN ; Wei-Quan HUANG ; Jing HUANG ; Sheng-Xi WU ; Hai-Chao HAN ; Li-Fan ZHANG
Acta Physiologica Sinica 2012;64(1):14-26
The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure. This study consisted of two interconnected series of in-vivo and ex-vivo experiments. In the in-vivo experiments, the tail-suspended, hindlimb unloaded rat model was used to simulate microgravity-induced cardiovascular deconditioning for 28 days (SUS group); and during the simulation period, another group was subjected to daily 1-hour dorso-ventral (-G(x)) gravitation provided by restoring to normal standing posture (S + D group). The activity of vascular L-RAS was evaluated by examining the gene and protein expression of angiotensinogen (Ao) and angiotensin II receptor type 1 (AT1R) in the arterial wall tissue. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. And for both arteries, the most prominent changes were in the innermost SM layers. Immunohistochemistry and in situ hybridization revealed that SUS induced an up- and down-regulation of Ao and AT1R expression in the vessel wall of common carotid artery and abdominal aorta, respectively, which was further confirmed by Western blot analysis and real time PCR analysis. Daily 1-hour restoring to normal standing posture over 28 days fully prevented these remodeling and L-RAS changes in the large elastic arteries that might occur due to SUS alone. In the ex-vivo experiments, to elucidate the important role of transmural pressure in vascular regional remodeling and differential regulation of L-RAS activity, we established an organ culture system in which rat common carotid artery, held at in-vivo length, can be perfused and pressurized at varied flow and pressure for 7 days. In arteries perfused at a flow rate of 7.9 mL/min and pressurized at 150 mmHg, but not at 0 or 80 mmHg, for 3 days led to an augmentation of c-fibronectin (c-FN) expression, which was also more markedly expressed in the innermost SM layers, and an increase in Ang II production detected in the perfusion fluid. However, the enhanced c-FN expression and increased Ang II production that might occur due to a sustained high perfusion pressure alone were fully prevented by daily restoration to 0 or 80 mmHg for a short duration. These findings from in-vivo and ex-vivo experiments have provided evidence supporting our hypothesis that redistribution of transmural pressures might be the primary factor that initiates region-specific remodeling of arteries during microgravity and the mechanism of IAG is associated with an intermittent restoration of the transmural pressures to their normal distribution. And they also provide support to the hypothesis that L-RAS plays an important role in vascular adaptation to microgravity and its prevention by the IAG countermeasure.
Angiotensinogen
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genetics
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metabolism
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Animals
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Aorta, Abdominal
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pathology
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physiopathology
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Carotid Artery, Common
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pathology
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physiopathology
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Hindlimb Suspension
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Male
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Muscle, Smooth, Vascular
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metabolism
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pathology
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RNA, Messenger
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genetics
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metabolism
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Rats
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Rats, Sprague-Dawley
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Receptor, Angiotensin, Type 1
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genetics
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metabolism
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Renin-Angiotensin System
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physiology
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Weightlessness Simulation
7.Effect evaluation of cognitive intervention on nurses' early discovery of hip dislocation
Gai-Yan WEI ; Xiao-Zhen CHEN ; Su-Yan YANG ; Qian LIN ; Yan LIU ; Jiu-Hui HAN
Chinese Journal of Modern Nursing 2013;19(17):2027-2028
Objective To explore the effect of cognitive intervention on nurses' early discovery of developmental dislocation of hip (DDH),in order to implement early treatment.Methods A totals of 30 nurses were chosen to have cognitive intervention on DDH,and their detectable rate of DDH positive was compared before and after.Results Nurses' detectable rate of DDH positive was 0.15% before intervention and 0.40% after,and the difference was statistically significant (x2 =6.798,P < 0.05).Confirmed diagnostic rate of DDH in newborns was 12.5% before intervention and 90.9% after,and the difference was statistically significant (x2 =4.078,P < 0.05).Conclusions Cognitive intervention can improve nurses' detectable rate of DDH to achieve early discovery and early treatment,reduce disability rate and the burden of family and society.
8.Protective effect of Yiqi Huoxue decoction on kidney in diabetic GK rats.
Jiu-Ling DENG ; Liang CHEN ; Qi-Yang SHOU ; Qi-Han LUO ; Hui-Ming WANG ; Hui WANG
China Journal of Chinese Materia Medica 2018;43(11):2372-2377
To investigate the protective effect of Yiqi Huoxue decoction on the kidney in diabetic goto-Kaizaki (GK) rats. Eight Wistar rats were used as normal control group. According to body weight and blood glucose, 16 GK rats were randomly divided into model control group and Yiqi Huoxue group, with 8 rats in each group. Drugs were administrated for 6 weeks. The rats were weighed and fasting blood glucose (FBG) were measured weekly; the glycosylated hemoglobin (HbALc) and 24 h metabolic rate were measured at the end of third and sixth weeks, at the same time, urine was collected to measure urinary glucose (U-GLU), urinary creatinine (U-CREA) and total proteinuria (U-TP) by biochemical method and calculate 24 h protein excretion rate (UAER). At the end of treatment, rats were sacrificed in anesthesia, and creatinin (CREA), uric acid (UA) and cholesterol (CHOL) were detected by biochemical method and glutathione peroxidase (GSH-Px) was detected by manual method with the blood drawn from heart. Both kidneys were taken and weighed to calculate the renal hypertrophy index. The kidneys were placed into neutral formalin and observed under light microscope for pathological change after Periodic Acid-Schiff (PAS) staining. The results showed that as compared with the normal control group, FBG, HbALc, 24 h Metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were significantly increased (<0.05) in the model group, while the body weight growth rate, serum GSH-Px level were significantly reduced(<0.05); in addition, renal glomerular injury and structural changes were observed in the model group. As compared with the model group, serum GSH-Px level was significantly increased (<0.05) in the Yiqi Huoxue group, While FBG, HbALc, 24 h Metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were significantly reduced (<0.05); meanwhile, renal glomerular injury and structural changes were improved in the Yiqi Huoxue group. The results showed that Yiqi Huoxue decoction can significantly increase serum GSH-Px level, reduce FBG, HbALc, 24 h metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index, and improve renal pathology in diabetic GK rats.
9.Anti-N-methyl-D-aspartate receptor encephalitis in seven children.
Xiao-hui WANG ; Fang FANG ; Chang-hong DING ; Jun-lan LÜ ; Tong-li HAN ; Li-ying LIU ; Jiu-wei LI ; Yun WU ; Li-ying CUI ; Hai-tao REN ; Chun-ling XU
Chinese Journal of Pediatrics 2012;50(12):885-889
OBJECTIVETo study the clinical and laboratory features and diagnosis of the patient with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis in children.
METHODThe data of clinical feature, laboratory findings, and radiological manifestation were reviewed and analyzed.
RESULTOf the 7 patients, 4 were female and 3 were male. The age of onset was from 6.6 to 15.5 years (average 9.5 years). The onset of 4 cases started with convulsion. Six cases had seizures which was difficult to control by antiepileptic drugs. All patients had psychiatric symptoms and speech disorder. Six cases had different levels of decreased consciousness and dyskinesias. 6 cases had autonomic nerve instability, and 7 cases developed sleep disorders. The results of MRI examination were normal in all patients. The EEG of most patients showed focal or diffuse slow waves. Six cases had oligoclonal bands. All cases were confirmed to have the disease by detection of anti-NMDA receptor antibodies. No tumor was detected in any of the patients. All patients received immunotherapy.
CONCLUSIONAnti-NMDAR encephalitis is a severe but treatable disorder that frequently affects children and adolescents. Pediatric patients had clinical manifestations similar to those of adult patients. But children have a lower incidence of tumors and hypoventilation also occurs less frequently in children. Most of children had a good prognosis.
Adolescent ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; complications ; diagnosis ; therapy ; Autoantibodies ; blood ; cerebrospinal fluid ; Autonomic Nervous System ; physiopathology ; Brain ; diagnostic imaging ; pathology ; Child ; Electroencephalography ; Female ; Humans ; Immunotherapy ; methods ; Magnetic Resonance Imaging ; Male ; Movement Disorders ; etiology ; Radiography ; Receptors, N-Methyl-D-Aspartate ; immunology ; Retrospective Studies ; Seizures ; etiology
10.Correlation of circulating tumor DNA EGFR mutation levels with clinical outcomes in patients with advanced lung adenocarcinoma.
Xiang-Liang LIU ; Ri-Lan BAI ; Xiao CHEN ; Yu-Guang ZHAO ; Xu WANG ; Ke-Wei MA ; Hui-Min TIAN ; Fu-Jun HAN ; Zi-Ling LIU ; Lei YANG ; Wei LI ; Fei GAI ; Jiu-Wei CUI
Chinese Medical Journal 2021;134(20):2430-2437
BACKGROUND:
Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma.
METHODS:
A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables.
RESULTS:
The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014).
CONCLUSIONS
Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.
Adenocarcinoma of Lung/genetics*
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Circulating Tumor DNA/genetics*
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ErbB Receptors/genetics*
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Humans
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Lung Neoplasms/genetics*
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Mutation/genetics*
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Protein Kinase Inhibitors