1.Morphological classification of postero-superior protuberance of calcaneus and its relationship with Haglund deformity.
Lei ZHANG ; Man ZHANG ; Lu JIANG ; Lei HUANG ; Yu WU ; Rao LENG ; Houyin SHI ; Guoyou WANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):592-597
OBJECTIVE:
To explore the morphological characteristics of the postero-superior protuberance of the calcaneus and to explore its relationship with Haglund malformation.
METHODS:
Ankle lateral X-ray films of 391 hospitalized patients between May 2021 and June 2024 were retrospectively collected. The morphological parameters of the postero-superior protuberance of the calcaneus were measured, including the length of the base, the height of the base, and the tip angle of the postero-superior protuberance of the calcaneus, and the morphological types were classified according to the above parameters, including the peak type, the hill type, and the flat type. The related parameters of Haglund malformation were measured, including Fowler-Philipp angle (FPA), calcaneal pitch angle (CPA), parallel pitch line (PPL), Chauveaux-Liet angle (CLA), and X/Y ratio (total calcaneal length/length of greater tuberosity of calcaneus). The differences of the morphological parameters of the postero-superior protuberance of the calcaneus and the related indicators of Haglund deformity among the three types and between the males and the females were compared and analyzed, and the differences of the positive numbers of the related indicators of Haglund deformity among the three types were compared.
RESULTS:
According to the morphological parameters of the postero-superior protuberance of the calcaneus, there were 64 cases of peak type, 245 cases of hill type, and 82 cases of flat type. There was no significant difference in the length of the base of the postero-superior protuberance of the calcaneus, CPA, CLA, and X/Y ratio among the three types ( P>0.05). Among the three types, the peak type had the largest FPA and the flat type had the smallest ( P<0.05); the peak type had the smallest tip angle of the postero-superior protuberance of the calcaneus and the flat type had the largest ( P<0.05); the positive rate of PPL in the hill type was significantly higher than that in the peak type and flat type ( P<0.05); the height of the base of the postero-superior protuberance of the calcaneus in the flat type was the smallest ( P<0.05). FPA, CPA, CLA, PPL, and X/Y ratio were positive in 2, 42, 172, 142, and 77 patients, respectively. There was no significant difference in the number of positive Haglund deformity indicators among the three types ( P>0.05). There was no significant difference between male and female patients in the tip angle of the postero-superior protuberance of the calcaneus, FPA, the positive rate of PPL, and X/Y ratio ( P>0.05). The length and the height of the base of the postero-superior protuberance of the calcaneus, CPA, and CLA in male patients were significantly higher than those in female patients ( P<0.05).
CONCLUSION
The postero-superior protuberance of the calcaneus can be divided into three types: the peak type, the hill type, and the flat type. The peak type is more likely to suffer from Haglund deformity, and the males are more likely to suffer from Haglund deformity than the females.
Humans
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Calcaneus/anatomy & histology*
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Male
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Female
;
Retrospective Studies
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Adult
;
Middle Aged
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Adolescent
;
Young Adult
;
Radiography
;
Child
;
Aged
2.Construction and validation of a prognostic prediction model for pediatric sepsis based on the Phoenix sepsis score.
Yongtian LUO ; Hui SUN ; Zhigui JIANG ; Zhen YANG ; Chengxi LU ; Lufei RAO ; Tingting PAN ; Yuxin RAO ; Xiao LI ; Honglan YANG
Chinese Critical Care Medicine 2025;37(9):856-860
OBJECTIVE:
To construct and validate a prognostic prediction model for children with sepsis using the Phoenix sepsis score (PSS).
METHODS:
A retrospective case series study was conducted to collect clinical data of children with sepsis admitted to the pediatric intensive care unit (PICU) of the Affiliated Hospital of Guizhou Medical University from January 2022 to April 2024. The data included general information, the worst values of laboratory indicators within the first 24 hours of PICU admission, PSS score, pediatric critical illness score (PCIS), and the survival status of the children within 30 days of admission. The statistically significant indicators in univariate Logistic regression analysis were included in multivariate Logistic regression analysis to screen the risk factors affecting the prognosis of children with sepsis and construct a nomogram model. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive performance of the model. The Bootstrap method was used to perform 1 000 repeated sampling internal verification and draw the calibration curve of the model.
RESULTS:
A total of 199 children with sepsis were included, of which 32 died and 167 survived 30 days after admission. In the univariate Logistic regression analysis, shock, white blood cell count (WBC), international normalized ratio (INR), lactic acid (Lac), PSS score, and PCIS score were identified as statistically significant predictors. These variables were then included in the multivariate Logistic regression analysis, which demonstrated that shock [odds ratio (OR) = 4.258, 95% confidence interval (95%CI) was 1.049-17.288], WBC (OR = 1.124, 95%CI was 1.052-1.210), and PSS score (OR = 1.977, 95%CI was 1.298-3.012) were independent risk factors for mortality in pediatric patients with sepsis (all P < 0.05). A nomogram model was constructed based on these three risk factors, with the model equation as follows: -4.809+1.449×shock+0.682×PSS score+0.117×WBC. The calibration curve results showed that the model's predictions were highly consistent with the actual observations. The ROC curve showed that when the Youden index of the prediction model was 0.792, the sensitivity and specificity were 90.6% and 88.6%, respectively, and the area under the curve (AUC) was 0.957 (95%CI was 0.930-0.984), which was higher than the AUC of shock, WBC, and PSS score alone (0.808, 0.667, 0.908, respectively).
CONCLUSIONS
Shock, WBC, and PSS score have demonstrated certain predictive value for mortality in children with sepsis. The nomogram model based on the above indicators has important clinical significance for evaluating the prognosis and guiding treatment of children with sepsis.
Humans
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Sepsis/diagnosis*
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Prognosis
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Retrospective Studies
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Logistic Models
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Intensive Care Units, Pediatric
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Nomograms
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Child
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ROC Curve
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Risk Factors
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Male
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Female
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Child, Preschool
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Infant
3.Species identification and antimicrobial resistance of bacteria isolated from sepsis patients in a tertiary hospital in Shanghai from 2021 to 2024
Panpan LYU ; Guihua RAO ; Qiang WANG ; Yue JIANG ; Fang ZHAO ; Mingliang CHEN
Chinese Journal of Microbiology and Immunology 2025;45(7):560-566
Objective:To identify the bacteria isolated from sepsis patients in a tertiary hospital in Shanghai and analyze their antimicrobial resistance features.Methods:This study included 439 patients with clinically diagnosed sepsis who underwent microbiological culture in a tertiary hospital in Shanghai from July 2021 to October 2024. Results of microbiological culture and antimicrobial susceptibility testing were retrospectively collected and analyzed. Differences between groups were analyzed using Chi-square test and Fisher′s exact test. Results:The positive rate of microbiological culture was 49.0% (215/439). The positive rate of blood culture was 24.1% (93/386) and 100 strains were isolated from the samples, including 57 Gram-negative bacteria (57.0%). The predominant isolates in blood samples were Escherichia coli, Klebsiella pneumoniae, and coagulase-negative staphylococci. The positive rate of bacterial culture from bronchoalveolar lavage fluid samples was 84.1% (37/44), with Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa being the predominant strains. The positive rate of bacterial culture from urine samples was 35.6% (127/357), with Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium being the most common. Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, coagulase-negative staphylococci, Pseudomonas aeruginosa, and Acinetobacter baumannii exhibited high resistance rates to fluoroquinolones [46.8% (29/62)-97.0% (32/33)]. The resistance rates of Acinetobacter baumannii to most commonly used antibiotics were >80.0%. The resistance rates of Escherichia coli and Klebsiella pneumoniae to the third-generation cephalosporins ranged from 41.8% (28/67) to 66.0% (31/47). Carbapenem resistance was observed in 38.1% (24/63)-40.3% (25/62) of Klebsiella pneumoniae isolates, and most of the isolates from bronchoalveolar lavage fluid samples showed a higher resistance rate than those from blood or urine samples ( P<0.05). Conclusions:The positive rate of bacterial culture is nearly 50% in this study, with Gram-negative bacteria being the most common. Six major pathogenic bacteria exhibit high resistance rates to fluoroquinolones. Klebsiella pneumoniae isolates have high resistance rates to the third-generation cephalosporins and carbapenems, with significant differences in the resistance rate between isolates from different samples, and it should be cautious to choose the third-generation cephalosporins and carbapenems in clinical practice.
4.Comparison of biomechanical characteristics of superior and inferior pubic ramus fractures fixed with different internal fixation methods
Xin RAO ; Daixiang JIANG ; Hui LU ; Yangxing LUO ; Meng LI ; Dingxi LIU ; Qimei WU ; Rong LIU
Chinese Journal of Tissue Engineering Research 2025;29(27):5757-5764
BACKGROUND:Percutaneous retrograde screws and minimally invasive percutaneous plates are extensively used in the treatment of unilateral pubic ramus fractures.However,the above internal fixations have the disadvantages of mistakenly penetrating the hip joint and damaging the medial pelvic trophoblastic artery.A new type of retrograde superior pubic ramus intramedullary nail offers advantages,such as fewer radiographic exposures and shorter surgery times,but the validation of the biomechanical properties of the three endoprostheses is lacking.OBJECTIVE:To compare the biomechanical differences post-treatment of upper and lower pubic ramus fractures using percutaneous retrograde screws,minimally invasive percutaneous plates,and retrograde superior pubic ramus intramedullary nail under various conditions through finite element analysis.METHODS:Pelvic CT data were collected from one volunteer and imported into Mimics 20,Geomagic Wrap 2021,and SolidWorks 2019 to create geometric models of three types of internal fixation for treating unilateral pubic ramus fractures:hollow screw group,plate group,and intramedullary nail group.Each model was imported into Ansys 2022 software,where it was set up in vertical,book-opening,and shear conditions for preprocessing and calculation to compare and analyze the mechanical stability of the implants.RESULTS AND CONCLUSION:(1)In vertical conditions,the biomechanical stability of the hollow screw treatment for unilateral pubic fractures was superior to that of the steel plate and intramedullary nail,with the smallest peak stress in the implant,which was four times lower compared to the other two groups.(2)In book-opening conditions,the steel plate treatment for unilateral pubic fractures showed better biomechanical stability,particularly in reducing stress at the fracture ends of the upper pubic branch,with stress values five times higher in the other two groups.(3)In shear conditions,the intramedullary nail treatment for unilateral pubic fractures exhibited good biomechanical stability,maintaining the best pelvic displacement,with a 25%greater displacement observed in the other two groups.(4)These findings reveal the biomechanical differences of different implants:the peak stress of implants is the smallest under vertical working conditions with percutaneous retrograde screws.Minimally invasive percutaneous plates reduce the stress at the broken end of superior pubic branch under open-book working condition.Retrograde superior pubic ramus intramedullary nail of superior pubic branch maintains pelvic displacement under shear working condition.The surgeon can combine the biomechanical differences of the implants with the actual situation of pubic injury in clinical practice to make the best implant treatment.
5.Quantitative trait locus(QTL) mapping and candidate gene expression analysis of cold tolerance of rice at plumule and seedling stages.
Beibei ZHAO ; Zhining ZHANG ; Yanan JIANG ; Chengxiang HU ; Luyi ZHANG ; Jun LIU ; Jiangmin XU ; Yuexing WANG ; Yuchun RAO
Chinese Journal of Biotechnology 2025;41(10):3939-3955
Rice (Oryza sativa L.), as a thermophilic crop, is highly susceptible to cold stress during its growth process. Chilling injury at the plumule stage and seedling stage often affects the morphological development and leads to yield reduction of rice. The exploration and utilization of cold tolerance genes are among the most direct and effective approaches to address cold stress in rice. To identify quantitative trait loci (QTLs) associated with cold tolerance at plumule and seedling stages, in this study, we measured the seedling rates and survived seedling rates of the indica rice cultivar 'HZ', the japonica cultivar 'Nekken2', and their 120 recombinant inbred lines (RILs) under cold stress. A previously constructed high-density genetic linkage map was used for the mapping of the QTLs conferring cold tolerance at the plumule and seedling stages. A total of 4 QTLs for plumule-stage cold tolerance and 9 QTLs for seedling-stage cold tolerance were detected, with the maximum limit of detection reaching 5.20. Notably, a genetically overlapping QTL for both plumule and seedling stages was identified on chromosome 8, spanning a physical interval of 24 432 953-25 295 129 bp. Candidate genes within the detected QTL intervals were screened, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the gene expression during the plumule and seedling stages. The results revealed that LOC_Os03g06570, LOC_Os03g07100, LOC_Os06g08280, LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540 exhibited significantly differential expression between the parental lines. These genes were either significantly downregulated or upregulated under cold stress. Among them, the first three gene (LOC_Os03g06570, LOC_Os03g07100, and LOC_Os06g08280) were hypothesized to be key candidates regulating the cold tolerance of rice seedlings, while the latter three genes (LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540) were identified as comprehensive regulators of cold tolerance during both plumule and seedling stages. These findings lay a foundation for the fine mapping and cloning of cold tolerance genes at the plumule and seedling stages, providing valuable insights for breeding cold-tolerant rice varieties.
Quantitative Trait Loci/genetics*
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Oryza/growth & development*
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Seedlings/growth & development*
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Cold Temperature
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Chromosome Mapping
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Gene Expression Regulation, Plant
6.Synthesis and Application of Salicylhydrazone Probe for Highly Selective Detection of Al3+
Hao-Xue TAN ; Zhong-Long WANG ; Xiao-Qin YANG ; Xiao-Ping RAO ; Ping ZHAO ; Qian JIANG
Chinese Journal of Analytical Chemistry 2025;53(2):214-223,中插3-中插12
In this work,four salicylhydrazone compounds(L1?L4)were designed and synthesized by using vanillin derivatives as raw material.The structures were confirmed by nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HRMS).The optical experiments showed that probe L1 and probe L3 could be used as aluminium ion(Al3+)fluorescence probes.The fluorescence color of probe L1 solution changed from colorless to blue after adding Al3+,and the limit of detection was 25.1 nmol/L.Compared with probe L1,the fluorescence color of probe L3 solution changed from colorless to green after complexing with Al3+,and the limit of detection was 17.3 nmol/L.Probe L1 and probe L3 showed the advantages of fast response speed,high selectivity and good anti-interference.The mechanism of Al3+recognition was further demonstrated by HRMS and 1H NMR.Cell imaging experiments showed that probe L1 and L3 had low cytotoxicity and had great application potential in detection of Al3+in vivo.
7.In-Situ Controlled Growth of NiCr Layered Double Hydroxide Nanosheets on Nichrome Alloy Fibers for Solid Phase Microextraction of Chlorophenols
Hai-Xia LIU ; Hong-Hong RAO ; Fang LIU ; Yan-Ping ZHENG ; Yong-Qiang JIANG
Chinese Journal of Analytical Chemistry 2025;53(3):481-491,后插1-后插4,封3
Nichrome(NiCr)wire with strong mechanical properties,excellent flexibility,good corrosion resistance and high thermal stability was selected as a promising fiber substrate to replace the fragile fused-silica counterpart.The NiCr layered double hydroxide nanosheets(NiCr LDHs NSs)were in-situ grown on the NiCr fiber substrate.Then,the extraction performance of the NiCr@NiCr LDHs NSs fiber was evaluated using four kinds of chlorophenol(CPs)as model compounds combined with high performance liquid chromatography-ultraviolet detection(HPLC-UV).The results showed that the assembled fibers exhibited superior extraction selectivity and enhanced extraction efficiency for CPs in comparison to commercial PA,PDMS,and PDMS/DVB fibers.Under the optimized experimental conditions,the established method showed good linearity in the range of 0.2-200 μg/L,with coefficient of determination(R2)>0.9989.The limits of detection(LODs)and limits of quantification(LOQs)were 0.050-0.157 μg/L and 0.165-0.502 μg/L,respectively.Relative standard deviations(RSDs)for intra-day and inter-day analyses ranged from 2.85%to 4.05%and from 3.16%to 4.96%,respectively.The developed method with the constructed fiber was applied to preconcentration and detection of different types of CPs in real water samples,showing satisfactory recoveries ranging from 80.0%to 106.9%,with RSDs of 3.12%-7.81%.Moreover,the NiCr@NiCr LDHs NSs fiber could maintain good extraction performance even after 240 extraction-desorption cycles.
8.BCCIP promotes resistance of gastric cancer to cisplatin by modulating DNA damage repair pathways
Zhe JIA ; Guangyan ZENG ; Peng ZOU ; Zongli FU ; Chuzhou ZHOU ; Xionghui RAO ; Yuhang ZHOU ; Chao JIANG ; Xinghan JIN ; Nuoqing WENG ; Huixing LUO
Chinese Journal of Pathophysiology 2025;41(5):871-881
AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.
9.Farrerol relaxes isolated pulmonary arteries in C57BL/6J mice by activating Kv channel
Keyu ZHANG ; Xiaomin HOU ; Jiajia ZOU ; Guojiao RAO ; Xuelu JIANG ; Lin DONG ; Yiwei SHI ; Xiaojiang QIN
Chinese Journal of Arteriosclerosis 2025;33(3):202-208
Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4 ℃ K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pul-monary artery rings were treated with different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1 μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experi-ment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concen-trations of PE(10-9,3×10-9,10-8,3 × 10-8,10-7,3×10-7 and 10-6 mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were meas-ured in the state of calcium free or recalcification { 2.5 mmol/L[Ca2+]ex }.(5)The relationship between farrerol in-duced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tet-raethylammonium(TEA),30 μmol/L BaCl2,and 10 μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-dependent relaxing effect on the mouse pulmonary arteries pre-contracted with PE and KCl.While the pretreatment of 3×10-5 mol/L farrerol could sig-nificantly reduce the maximum contraction of mouse pulmonary arteries induced by PE and KCl(P<0.01),as well as sig-nificantly reduce the contraction of mouse pulmonary arteries induced by KCl under calcium free or recalcification conditions(P<0.01).Addition of the voltage-dependent potassium ion channel blocker 4-AP significantly reduced the maximum diastolic rate of mouse pulmonary arteries induced by farrerol(P<0.01),while addition of the high conductivity calcium activated potassium ion channel blocker TEA,inward rectifying potassium ion channel blocker BaCl2,or ATP sensitive po-tassium ion channel blocker Gli had no significant effect on the vasodilation effect of farrerol(P>0.05).Conclusion Farrerol has a relaxing effect on isolated mouse pulmonary arteries,and its mechanism may be related to open voltage-de-pendent potassium ion channels.
10.Analysis of MET gene variation and clinicopathological characteristics of non-small cell lung cancer
Qiong ZHANG ; Yang SHEN ; Zhenhong JIANG ; Jianping HU ; Xinyu LONG ; Zhiqing CHEN ; Yuting RAO ; Yan ZHENG ; Yeqing ZOU
Chinese Journal of Clinical and Experimental Pathology 2025;41(6):713-718
Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53%(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P<0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P>0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P<0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62%of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P<0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

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