1.Analysis of the metabolic profile in 4-minute low-volume high-intensity intermittent training based on the W'balance model
Junchao YANG ; Zhihui LU ; Xiangxin LI ; Xueyuan ZHAO ; Junqiang QIU
Chinese Journal of Sports Medicine 2025;44(5):358-364
Objective To evaluate the effectiveness of low-volume high-intensity interval training(LV-HIIT)protocols defined by the W'Balance(W'BAL)model in achieving maximal activation of both anaerobic and aerobic energy systems.Methods Twenty-eight national-level athletes(age:20±1 years old;height:174±9 cm;weight:65.1±9.4 kg)completed an incremental exercise test,followed by six supra-critical power(supra-CP)and five sub-CP constant-load tests to determine VO2max,maximal accumulated oxygen deficit(MAOD),critical power(CP),and W prime(W').They then performed three randomly ordered LV-HIIT protocols(each of 4-minute total duration),with a 10-second inter-val for passive recovery between bouts.The protocols consisted of 10s(HIIT10/10),20s(HIIT20/10),and 30 s(HIIT30/10).Exercise intensities were individually prescribed using the W'BAL model.Accu-mulated oxygen deficit(AOD)and net AOD(NAOD)were calculated for each protocol.Results Final 10-s oxygen uptake(VO2)reached 77%,88%,and 89%of VO2max in HIIT10/10,HIIT20/10,and HIIT30/10,respectively(P<0.05).VO2 in HIIT10/10 was significantly lower than in HIIT20/10 and HIIT30/10(P<0.05),with no significant difference between the latter two(P>0.05).AOD did not differ significantly from MAOD among the three protocols(P>0.05),whereas NAOD was significantly lower than MAOD in all cases(P<0.05).Additionally,NAOD in HIIT10/10 was significantly lower than in HIIT20/10 and HI-IT30/10(P<0.05),with no significant difference between the latter two(P>0.05).Conclusion The HIIT20/10 and HIIT30/10 intensity established by the W'BAL model can substantially elicit maximal activation of both anaerobic and aerobic energy systems.While the W'BAL model demonstrates potential for set-ting exercise intensities in LV-HIIT,future studies are necessary to develop specific W'recovery rate models for targeted populations and to refine CP models that are better suited for intermittent exercises.
2.Effectiveness of predicting ventilatory and lactate thresholds using a combination of muscle oxygenation and heart rate variability
Xiangxin LI ; Junchao YANG ; Zhihui LU ; Kuan TAO ; Junqiang QIU
Chinese Journal of Sports Medicine 2025;44(7):537-549
Objective To compare the effectiveness of the heart rate variability threshold(HRVT),muscle oxygenation threshold(MOT),and their combined threshold(COMT)in predicting the ventila-tory threshold(VT)and lactate threshold(LT).Methods Twenty male athletes at or above the nation-al level were recruited to perform an incremental exercise test to determine VT and LT,during which gas exchange,muscle oxygenation,and heart rate variability were collected.The HRVT,MOT,and COMT methods were then applied,and their predictive validity was evaluated by comparing the correla-tions and agreements between heart rate(HR)and power output(PO)at VT and LT.Results For HR,VT1 showed strong correlation and agreement with MOT1(r=0.958,ICC=0.944)and COMT1(r=0.957,ICC=0.951),with COMT1 having the smallest mean bias(1.4 bpm)and the narrowest limits of agreement(LOA)(-5.4 to 8.2 bpm).Moreover,VT2 demonstrated the highest correlation and agree-ment with COMT2(r=0.985,ICC=0.982),with a mean bias of-0.7 bpm and LOA of-5.0 to 3.7 bpm.Meanwhile,LT showed high correlation and good agreement with COMT2(r=0.884,ICC=0.754)and MOT2(r=0.886,ICC=0.738),with mean biases of-6.8 bpm and-7.3 bpm,and LOA of-17.5 to 3.8 bpm and-17.9 to 3.2 bpm,respectively.For PO,VT1 had the best correlation and agreement with MOT1(r=0.836,ICC=0.808),with a mean bias of-0.2 W and LOA of-11.7 to 11.3 W.VT2 performed best correlation and agreement with COMT2(r=0.910,ICC=0.900),with a mean bias of 2.3 W and LOA of-8.9 to 13.5 W.In LT prediction,MOT2(r=0.736,ICC=0.692)outperformed COMT2(r=0.635,ICC=0.618),with mean biases of-2.6 W and 0.2 W,and LOA of-26.0 to 20.7 W and-26.6 to 27.1 W,respectively.Conclusion All three indicators—HRVT,MOT,and COMT—demonstrates high validity in predicting VT and LT.MOT1 performs best for predicting PO at VT1,while COMT2 shows the highest consistency for predicting both HR and PO at VT2.Howev-er,for LT prediction,MOT2 is more advantageous for predicting PO,whereas COMT2 is more accu-rate for predicting HR.Therefore,method selection should be tailored to the specific threshold type and measurement target.
3.Effects of hypoxic exercise on Irisin secretion in obese rats and lipid-deposited L6 myoblasts
Peiyuan LI ; Junpeng FENG ; Mingyue LU ; Kaixuan CHE ; Zhihui LU ; Junqiang QIU
Chinese Journal of Sports Medicine 2025;44(10):813-820
Objective To explore the effect of hypoxic exercise on Irisin secretion of obese rats with a palmitic acid-induced lipid accumulation in L6 myotubes and a high-fat diet-induced model.Methods L6 myotubes were treated with 750 μmol/L palmitic acid to induce lipid accumulation and subsequently divided into four groups of normoxia(N),exercise(E),hypoxia(H),and hypoxic exer-cise(HE).Hypoxic conditions(1%O2)were used to simulate a low-oxygen environment,while AICAR stimulation was applied to the E and HE groups to mimic exercise.Eighty 3-week-old Sprague-Dawley rats were fed a high-fat diet for 16 weeks to establish an obesity model.Fifty obese rats that met the criteria were then selected and randomly assigned according to their body weight into five groups of normoxia-sedentary(NC),normoxia-exercise(NE),hypoxia-sedentary(HC),high-liv-ing high-training(HH),and low-living high-training(LH),each of 10.The hypoxic environment was set at 13.6%O2(simulating 3,500 m altitude).Then the NE,HH and LH groups performed daily one-hour treadmill training(NE:20 m/min;HH and LH:16 m/min),5 days/week for 4 weeks.After the intervention,the body composition was measured using dual-energy X-ray absorptiometry(DEXA),while Irisin concentrations in cell culture media and rat serum were determined by using the enzyme-linked immunosorbent assay.Moreover,fibronectin type Ⅲ domain-containing 5(FNDC5)mRNA expression in L6 cells and rat skeletal muscle was measured by quantitative polymerase chain reaction(qPCR),while FNDC5 and silent information regulator 1-peroxisome proliferators-activated re-ceptor γ coactivator lalpha(SIRT1-PGC-1α)pathway proteins were analyzed using Western blotting.Results(1)Cell experiments:①Compared with the N group,there were significantly higher Irisin lev-els in the culture medium of the E,H,and HE groups(P<0.01,P<0.05),as well as elevated FNDC5 mRNA and protein expression in the E and HE groups(P<0.05,P<0.01).Moreover,the Iri-sin concentration and FNDC5 protein levels of group HE were significantly higher than group E(P<0.05).②Compared with group N,significantly increased SIRT1 and PGC-1α protein expression was observed in groups E and HE(P<0.05,P<0.01).(2)Animal experiments:①Compared with the NC group,body weight and fat mass were significantly lower in the NE,LH,and HH groups(P<0.01),with further reductions observed in the HH group compared with the NE group(P<0.05).② Com-pared with group NC,groups NE,LH,and HH exhibited higher serum Irisin levels and increased FNDC5 mRNA and protein expression in skeletal muscle(P<0.05,P<0.01).Furthermore,FNDC5 pro-tein expression of the HH group was significantly higher than the NE group(P<0.05).③ Compared with the NC group,SIRT1 and PGC-1α protein levels were significantly upregulated in the NE,LH,and HH groups(P<0.05,P<0.01).Conclusion Hypoxic exercise effectively alleviates obesity,reduces body weight and fat accumulation in high-fat diet-induced obese rats,and enhances FNDC5 expres-sion and Irisin secretion,which may be mediated through activation of the SIRT1-PGC-1α signaling pathway.Moreover,among the different hypoxic exercise modalities,the"high-living high-training"protocol appears to have greater benefits in promoting FNDC5/Irisin expression and facilitating weight and fat reduction in obese rats.
4.Effectiveness of predicting ventilatory and lactate thresholds using a combination of muscle oxygenation and heart rate variability
Xiangxin LI ; Junchao YANG ; Zhihui LU ; Kuan TAO ; Junqiang QIU
Chinese Journal of Sports Medicine 2025;44(7):537-549
Objective To compare the effectiveness of the heart rate variability threshold(HRVT),muscle oxygenation threshold(MOT),and their combined threshold(COMT)in predicting the ventila-tory threshold(VT)and lactate threshold(LT).Methods Twenty male athletes at or above the nation-al level were recruited to perform an incremental exercise test to determine VT and LT,during which gas exchange,muscle oxygenation,and heart rate variability were collected.The HRVT,MOT,and COMT methods were then applied,and their predictive validity was evaluated by comparing the correla-tions and agreements between heart rate(HR)and power output(PO)at VT and LT.Results For HR,VT1 showed strong correlation and agreement with MOT1(r=0.958,ICC=0.944)and COMT1(r=0.957,ICC=0.951),with COMT1 having the smallest mean bias(1.4 bpm)and the narrowest limits of agreement(LOA)(-5.4 to 8.2 bpm).Moreover,VT2 demonstrated the highest correlation and agree-ment with COMT2(r=0.985,ICC=0.982),with a mean bias of-0.7 bpm and LOA of-5.0 to 3.7 bpm.Meanwhile,LT showed high correlation and good agreement with COMT2(r=0.884,ICC=0.754)and MOT2(r=0.886,ICC=0.738),with mean biases of-6.8 bpm and-7.3 bpm,and LOA of-17.5 to 3.8 bpm and-17.9 to 3.2 bpm,respectively.For PO,VT1 had the best correlation and agreement with MOT1(r=0.836,ICC=0.808),with a mean bias of-0.2 W and LOA of-11.7 to 11.3 W.VT2 performed best correlation and agreement with COMT2(r=0.910,ICC=0.900),with a mean bias of 2.3 W and LOA of-8.9 to 13.5 W.In LT prediction,MOT2(r=0.736,ICC=0.692)outperformed COMT2(r=0.635,ICC=0.618),with mean biases of-2.6 W and 0.2 W,and LOA of-26.0 to 20.7 W and-26.6 to 27.1 W,respectively.Conclusion All three indicators—HRVT,MOT,and COMT—demonstrates high validity in predicting VT and LT.MOT1 performs best for predicting PO at VT1,while COMT2 shows the highest consistency for predicting both HR and PO at VT2.Howev-er,for LT prediction,MOT2 is more advantageous for predicting PO,whereas COMT2 is more accu-rate for predicting HR.Therefore,method selection should be tailored to the specific threshold type and measurement target.
5.Effects of hypoxic exercise on Irisin secretion in obese rats and lipid-deposited L6 myoblasts
Peiyuan LI ; Junpeng FENG ; Mingyue LU ; Kaixuan CHE ; Zhihui LU ; Junqiang QIU
Chinese Journal of Sports Medicine 2025;44(10):813-820
Objective To explore the effect of hypoxic exercise on Irisin secretion of obese rats with a palmitic acid-induced lipid accumulation in L6 myotubes and a high-fat diet-induced model.Methods L6 myotubes were treated with 750 μmol/L palmitic acid to induce lipid accumulation and subsequently divided into four groups of normoxia(N),exercise(E),hypoxia(H),and hypoxic exer-cise(HE).Hypoxic conditions(1%O2)were used to simulate a low-oxygen environment,while AICAR stimulation was applied to the E and HE groups to mimic exercise.Eighty 3-week-old Sprague-Dawley rats were fed a high-fat diet for 16 weeks to establish an obesity model.Fifty obese rats that met the criteria were then selected and randomly assigned according to their body weight into five groups of normoxia-sedentary(NC),normoxia-exercise(NE),hypoxia-sedentary(HC),high-liv-ing high-training(HH),and low-living high-training(LH),each of 10.The hypoxic environment was set at 13.6%O2(simulating 3,500 m altitude).Then the NE,HH and LH groups performed daily one-hour treadmill training(NE:20 m/min;HH and LH:16 m/min),5 days/week for 4 weeks.After the intervention,the body composition was measured using dual-energy X-ray absorptiometry(DEXA),while Irisin concentrations in cell culture media and rat serum were determined by using the enzyme-linked immunosorbent assay.Moreover,fibronectin type Ⅲ domain-containing 5(FNDC5)mRNA expression in L6 cells and rat skeletal muscle was measured by quantitative polymerase chain reaction(qPCR),while FNDC5 and silent information regulator 1-peroxisome proliferators-activated re-ceptor γ coactivator lalpha(SIRT1-PGC-1α)pathway proteins were analyzed using Western blotting.Results(1)Cell experiments:①Compared with the N group,there were significantly higher Irisin lev-els in the culture medium of the E,H,and HE groups(P<0.01,P<0.05),as well as elevated FNDC5 mRNA and protein expression in the E and HE groups(P<0.05,P<0.01).Moreover,the Iri-sin concentration and FNDC5 protein levels of group HE were significantly higher than group E(P<0.05).②Compared with group N,significantly increased SIRT1 and PGC-1α protein expression was observed in groups E and HE(P<0.05,P<0.01).(2)Animal experiments:①Compared with the NC group,body weight and fat mass were significantly lower in the NE,LH,and HH groups(P<0.01),with further reductions observed in the HH group compared with the NE group(P<0.05).② Com-pared with group NC,groups NE,LH,and HH exhibited higher serum Irisin levels and increased FNDC5 mRNA and protein expression in skeletal muscle(P<0.05,P<0.01).Furthermore,FNDC5 pro-tein expression of the HH group was significantly higher than the NE group(P<0.05).③ Compared with the NC group,SIRT1 and PGC-1α protein levels were significantly upregulated in the NE,LH,and HH groups(P<0.05,P<0.01).Conclusion Hypoxic exercise effectively alleviates obesity,reduces body weight and fat accumulation in high-fat diet-induced obese rats,and enhances FNDC5 expres-sion and Irisin secretion,which may be mediated through activation of the SIRT1-PGC-1α signaling pathway.Moreover,among the different hypoxic exercise modalities,the"high-living high-training"protocol appears to have greater benefits in promoting FNDC5/Irisin expression and facilitating weight and fat reduction in obese rats.
6.Analysis of the metabolic profile in 4-minute low-volume high-intensity intermittent training based on the W'balance model
Junchao YANG ; Zhihui LU ; Xiangxin LI ; Xueyuan ZHAO ; Junqiang QIU
Chinese Journal of Sports Medicine 2025;44(5):358-364
Objective To evaluate the effectiveness of low-volume high-intensity interval training(LV-HIIT)protocols defined by the W'Balance(W'BAL)model in achieving maximal activation of both anaerobic and aerobic energy systems.Methods Twenty-eight national-level athletes(age:20±1 years old;height:174±9 cm;weight:65.1±9.4 kg)completed an incremental exercise test,followed by six supra-critical power(supra-CP)and five sub-CP constant-load tests to determine VO2max,maximal accumulated oxygen deficit(MAOD),critical power(CP),and W prime(W').They then performed three randomly ordered LV-HIIT protocols(each of 4-minute total duration),with a 10-second inter-val for passive recovery between bouts.The protocols consisted of 10s(HIIT10/10),20s(HIIT20/10),and 30 s(HIIT30/10).Exercise intensities were individually prescribed using the W'BAL model.Accu-mulated oxygen deficit(AOD)and net AOD(NAOD)were calculated for each protocol.Results Final 10-s oxygen uptake(VO2)reached 77%,88%,and 89%of VO2max in HIIT10/10,HIIT20/10,and HIIT30/10,respectively(P<0.05).VO2 in HIIT10/10 was significantly lower than in HIIT20/10 and HIIT30/10(P<0.05),with no significant difference between the latter two(P>0.05).AOD did not differ significantly from MAOD among the three protocols(P>0.05),whereas NAOD was significantly lower than MAOD in all cases(P<0.05).Additionally,NAOD in HIIT10/10 was significantly lower than in HIIT20/10 and HI-IT30/10(P<0.05),with no significant difference between the latter two(P>0.05).Conclusion The HIIT20/10 and HIIT30/10 intensity established by the W'BAL model can substantially elicit maximal activation of both anaerobic and aerobic energy systems.While the W'BAL model demonstrates potential for set-ting exercise intensities in LV-HIIT,future studies are necessary to develop specific W'recovery rate models for targeted populations and to refine CP models that are better suited for intermittent exercises.
7.Clinical application of intravenous dexmedetomidine combined with target-controlled remifentanil in anesthesia of ERCP surgery in older adult patients
Ning CHEN ; Dandan SONG ; Zhihui QIU ; Ming XU ; Bo CUI ; Yugang DIAO
Journal of China Medical University 2024;53(1):39-45
Objective To explore the safety and feasibility of intravenous dexmedetomidine(Dex)combined with targeted infusion of remifentanil in endoscopic retrograde cholangiopancreatography(ERCP)anesthesia in older adult patients.Methods From January to August 2021,98 older adult patients(≥65 years old)undergoing ERCP were randomly divided into TRP and TRD groups.The TRP group was anesthetized with target-controlled infusion of propofol and remifentanil and the TRD group was treated with Dex combined with target-controlled infusion of remifentanil.mean arterial pressure(MAP),heart rate(HR),electrocardiogram(ECG),respiratory rate(RR),pulse oxygen saturation(SpO2),bispectral index(BIS)before anesthesia induction(T0),immediately after induction of anesthesia(T1),endoscopic introduction(T2),duodenal papilla intubation(T3),endoscopy withdrawal(T4)and postoperative awakening(T5)were observed.Arterial blood gas analysis at different time points(T0,every 15 min after anesthesia induction and T5),PaO2,and PaCO2,were recorded at the above mentioned time points;and the remifentanil concentration in target-controlled infusion,operation time,recovery time(from infusion of remifentanil to consciousness recovery),anesthesia recovery time(from consciousness recovery to leaving the operating room),intraoperative body movement,Aldrete scores out of the room,Visual Analogue Scale(VAS)at 60 min after surgery,occurrence of post-operative adverse reactions,as well as the satisfaction of anesthesiologists,endoscopists,and patients were recorded.Results Compared with the TRP group,MAP at T1 and T3,SpO2 and RR at T1,T2,T3,and T4,and BIS at T2,T3,T4,and T5 increased,whereas HR at T1,T2,T3,and T4 decreased;the number of mandibular rests,incidence of hypoxemia,Aldrete score,and satisfaction increased,whereas the VAS score at 60 min after surgery decreased in the TRD group(P<0.05).There were no statistically significant differences in postoperative adverse reactions,PaO2 and PaCO2,target-controlled infusion remifentanil concentration,operation time,recovery time,and anesthesia recovery time between the two groups.Conclusion Compared with the target-controlled infusion of propofol-remifentanil,intravenous infusion of Dex combined with target-controlled infusion of remifentanil can reduce the incidence of hypoxemia in older adult patients during ERCP surgery,and the anesthesia regimen can meet the anesthesia needs of ERCP surgery,which is safe and feasible.
8.Therapeuti ceffect and potential mechanism of cholesterol sulfate on a mouse model of Hashimoto's thyroiditis
Linye HE ; Huandi QIU ; Wei HE ; Yiguo HU ; Zhihui LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):105-111
Objective To investigate the therapeutic effect of cholesterol sulfate(CS)on the Hashimoto's thyroiditis mouse model.Methods Female NOD.H-2h4 mice were fed with 0.05%NaI in different periods and treated with CS by intraperitoneal injection for two consecutive weeks.HE staining was used to visualize and score the degree of lymphocyte infiltration in the thyroid;serum levels of thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb),thyroxine(T4),and thyroid stimulating hormone(TSH)were detected by ELISA.The proportions of B cells and Treg,Th17,Th1,and Th2 cells were analyzed by immunofluorescence staining flow cytometry.Results HE staining showed that the inflammatory score of thyroid tissue in mice after intraperitoneal injection of CS in the 8-week group and the 16-week group decreased significantly(P<0.05).In the 64-week group,there was no significant difference between the treatment group and the induction group(P=0.31).Serological analysis showed that after CS intervention,the levels of TgAb and TPOAb in mice induced by 0.05%NaI significantly lowered(P<0.05)in the 8-week group and the 16-week group,while thyroid function(TSH and T4 levels)of the mice changed significantly only in the 16-week group.Flow cytometry analysis showed that in the 8-week group,after CS intervention the proportions of B lymphocytes and Th1,Th2,Th17 and Treg cells in mice were significantly changed(P<0.05).Conclusion CS has significant therapeutic and remission effects on the early and middle stages of Hashimoto's thyroiditis.
9.Application of 9-gene panel in assisting fine needle aspiration cytology to diagnose thyroid cancer
Yanqi ZHANG ; Huan ZHAO ; Linlin ZHAO ; Yue SUN ; Cong WANG ; Zhihui ZHANG ; Tian QIU ; Xin YANG ; Ting XIAO ; Huiqin GUO
Chinese Journal of Oncology 2024;46(11):1049-1057
Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P<0.01), but there is no significant difference in SN, accuracy (both P>0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.
10.Application of 9-gene panel in assisting fine needle aspiration cytology to diagnose thyroid cancer
Yanqi ZHANG ; Huan ZHAO ; Linlin ZHAO ; Yue SUN ; Cong WANG ; Zhihui ZHANG ; Tian QIU ; Xin YANG ; Ting XIAO ; Huiqin GUO
Chinese Journal of Oncology 2024;46(11):1049-1057
Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P<0.01), but there is no significant difference in SN, accuracy (both P>0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

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