1.Study on the Effect of Liuwei Dihuang Pills on Regulating the Antigen Cross-Presenting Ability of Dendritic Cells by Interfering with Gap Junctional Communication Function
Yue SONG ; Man-Si XU ; Xue-Ying ZHONG ; Wen-Jing ZHANG ; Xiao-Yi CHEN ; Biao-Yan DU ; Jian-Yong XIAO ; Kun WANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):169-177
		                        		
		                        			
		                        			Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.
		                        		
		                        		
		                        		
		                        	
2.Construction of CRISPR/Cas9 knock-in system for tardigrade damage suppressor gene Dsup and its effect on HEK 293T cell proliferation
Yuting GAO ; Biao ZHANG ; Yali JIA ; Haiyang WANG ; Tao FAN ; Jiafei XI ; Wen YUE ; Quan ZENG ; Junnian ZHOU
Military Medical Sciences 2024;48(8):586-593
		                        		
		                        			
		                        			Objective To construct HEK 293T cells that express tardigrade Dsup protein fused with green fluorescent protein copGFP in order to study the effect of Dsup protein on proliferation of HEK 293T cells.Methods The CRISPR/Cas9 gene knock-in system was constructed.The target gene fragments of Dsup,copGFP,EF1α and puromycin were amplified by PCR and inserted into pAAVS1-SFFV to construct the fusion vector of Dsup and copGFP,which was known as pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro.pAAVS1-SFFV-Dsup-copGFP-EF1 α-Puro and pAAVS1-CRISPR-Cas9 vector were co-transfected into HEK 293T cells before Dsup gene was inserted into the AAVS1 region of HEK 293T cells via homologous recombination.The HEK 293T cells expressing Dsup gene were obtained following puromycin selection,flow cytometry sorting and genome identification.The expression of Dsup at mRNA and protein levels and proliferation-related genes(MCM2,MCM4,PCNA,Ki-67)were examined to investigate the effects of Dsup gene on the proliferation of HEK 293T-Dsup-copGFP cells.Results The pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro recombinant vector was constructed,and the HEK 293T-Dsup-copGFP cells with Dsup gene inserted in the AAVS1 region were obtained,where both Dsup mRNA and protein were expressed.The cell proliferation rate of HEK 293T-Dsup-copGFP was higher than that of HEK 293T-Control-copGFP(P<0.001).Further investigation revealed that the expressions of Ki-67 and MCM4 protein in HEK 293T-Dsup-copGFP were significantly higher than in the control group,indicating that the knock in of Dsup gene might enhance the proliferation ability of human cells by promoting the expression of Ki-67 and MCM4 protein.Conclusion A gene editing vector is constructed,and stable cell line HEK 293T-Dsup-copGFP for Dsup fusion expression with copGFP is established.The expression of Dsup gene in HEK 293T cells can promote cell proliferation,possibly by upregulating the expressions of Ki-67 and MCM4 protein.
		                        		
		                        		
		                        		
		                        	
3.Clinical Analysis of CD4+CD8-T-Cell Large Granular Lymphocytic Leukemia
Xiang-Xiang CHANG ; Shang-Biao SUN ; Yu-Wen LI ; Miao WANG ; Yan-Qing ZHU
Journal of Experimental Hematology 2024;32(5):1388-1393
		                        		
		                        			
		                        			Objective:To investigate the clinical characteristics and treatment of patients with CD4+CD8-T-cell large granular lymphocytic leukemia(T-LGLL).Methods:The clinical manifestations,diagnosis and treatment of 1 case of CD4+CD8-T-LGLL patient were reported,and relevant literatures were reviewed.Results:The patient was a 70-year-old woman with slow clinical progress,mainly manifested by thrombocytopenia and myelodysplasia.The blood smear was mainly composed of large granular lymphocytes.Immunotyping and T-cell receptor gene rearrangement analysis showed that it was in line with T-LGLL.Partial remission(PR)was achieved through the treatment of cyclophosphamide(50 mg/d)combined with prednisone(gradually reduced and stopped later).Conclusion:CD4+CD8-T-LGLL is very rare in clinical practice,and its clinical manifestations are different from those of CD4-CD8+T-LGLL.
		                        		
		                        		
		                        		
		                        	
4.Research on face mask recognition based on YOLOv5 lightweight network
Liang WEN ; Jiang WANG ; Guo-Biao LIANG ; Zhen-Ni LI
Chinese Medical Equipment Journal 2024;45(9):7-13
		                        		
		                        			
		                        			Objective To propose a YOLOv5 lightweight network-based face mask recognition method to solve the problems due to limited storage and computation resources of edge and mobile devices.Methods A YOLOv5 model composed of a backbone network(Backbone),a neck module(Neck)and a head module(Head)was selected as the base framework.Firstly,the Backbone part was modified and replaced using the ShuffleNetv2 lightweight network;secondly,a Ghost module and a C3_S module were introduced in the Neck part;finally,a Shuffle_Yolo_GS_CBAM model was formed by incorporating a convolutional block attention module(CBAM)to improve the detection accuracy.The model was trained and verified with the AIZOO dataset,which was evaluated for face mask recognition by mean average precision(mAP),frames per second(FPS),giga floating-point operations per second(GFLOPS)and parameters.Results The model proposed recognized face masks with the mAP being 89.5%,FPS being 158.7 frames/s,parameters being 2.38 M and and GFLOPS being 4.5 GFLOPS,which had the detection speed enhanced by 39.7%,parameters decreased by 67.3%and operations reduced by73.8%when compared with the YOLOv5s model.Conclusion The method proposed behaves well in increasing detection speed,decreasing parameters and operations and ensuring detection precision,and thus is worthy promoting for face mask recognition on edge and mobile devices.[Chinese Medical Equipment Journal,2024,45(9):7-13]
		                        		
		                        		
		                        		
		                        	
5.Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.
Xiao-Yun YIN ; Yun-Mei ZHANG ; Ai-Dong SHEN ; Jing-Ping WANG ; Zhe-Xun LIAN ; Yi-Bing SHAO ; Wen-Qi ZHANG ; Shu-Ying ZHANG ; Yang ZHENG ; Kang CHENG ; Biao XU ; Cheng-Xing SHEN ; Rong-Chong HUANG ; Jin-Cheng GUO ; Guo-Sheng FU ; Dong-Kai SHAN ; Dan-Dan LI ; Yun-Dai CHEN
Journal of Geriatric Cardiology 2023;20(4):256-267
		                        		
		                        			OBJECTIVE:
		                        			To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).
		                        		
		                        			METHODS:
		                        			In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.
		                        		
		                        			RESULTS:
		                        			Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.
		                        		
		                        			CONCLUSIONS
		                        			In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.
		                        		
		                        		
		                        		
		                        	
6.Diagnostic value of contrast-enhanced ultrasound in hepatic epithelioid hemangioendothelioma.
Ya Dan XU ; Han Tao WANG ; Yu Li ZHU ; Yi DONG ; Wei Bin ZHANG ; Wen Ping WANG ; Feng MAO ; Zheng Biao JI
Chinese Journal of Hepatology 2023;31(6):589-593
		                        		
		                        			
		                        			Objective: To investigate the features of contrast-enhanced ultrasound (CEUS) in hepatic epithelioid hemangioendothelioma (HEHE) in order to improve the preoperative diagnosis rate. Methods: CEUS images of 32 pathologically-proven cases of hepatic epithelioid hemangioendothelioma from January 2004 to August 2021 were collected. Lesions were analyzed to observe the features of enhancement mode, enhancement intensity, and distinct enhancement phases. Results: Among the 32 cases, one had a solitary lesion, 29 had multiple lesions, and two had diffuse-type lesions. Contrast-enhanced ultrasound revealed a total of 42 lesions in 32 cases. In terms of arterial phase enhancement, 18 lesions had overall enhancement, six lesions had uneven dendritic enhancement, 16 lesions had rim-like enhancement, and two lesions had just slight peripheral spot enhancement around the lesions. Among the three cases, there were multiple lesions that had overall enhancement and ring enhancement. In terms of the enhancement phase, 20 lesions showed "fast progression", 20 lesions showed "same progression", and two lesions showed "slow progression". During the late arterial or early portal venous phases with rapid washout, all lesions manifested as hypoechoic. With peaked enhanced intensity, 11 lesions had a lower enhancement intensity than the surrounding normal liver parenchyma; 11 lesions had the same enhancement degree as the surrounding normal liver parenchyma; and 20 lesions had a higher enhancement degree than the surrounding normal liver parenchyma. All 16 ring-enhancing lesions had marked hyperenhancement. In the typical enhancing lesions, four showed hyperenhancement, five showed low enhancement, and nine showed isoenhancement. In the dendrite-enhancing lesions, there were two isoenhancing and four hypoenhancing. Contrast-enhanced ultrasound delineated the boundaries of all lesions more clearly than two-dimensional ultrasound. Conclusion: Contrast-enhanced ultrasound has certain value in the diagnosis of hepatic epithelioid hemangioendothelioma.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hemangioendothelioma, Epithelioid/pathology*
		                        			;
		                        		
		                        			Contrast Media
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Liver Neoplasms/pathology*
		                        			;
		                        		
		                        			Portal Vein/pathology*
		                        			;
		                        		
		                        			Ultrasonography
		                        			
		                        		
		                        	
7.Associations between indoor volatile organic compounds and nocturnal heart rate variability of young female adults: A panel study.
Xue Zhao JI ; Shan LIU ; Wan Zhou WANG ; Ye Tong ZHAO ; Lu Yi LI ; Wen Lou ZHANG ; Guo Feng SHEN ; Fu Rong DENG ; Xin Biao GUO
Journal of Peking University(Health Sciences) 2023;55(3):488-494
		                        		
		                        			OBJECTIVE:
		                        			To investigate the association between short-term exposure to indoor total volatile organic compounds (TVOC) and nocturnal heart rate variability (HRV) among young female adults.
		                        		
		                        			METHODS:
		                        			This panel study recruited 50 young females from one university in Beijing, China from December 2021 to April 2022. All the participants underwent two sequential visits. During each visit, real time indoor TVOC concentration was monitored using an indoor air quality detector. The real time levels of indoor temperature, relative humidity, noise, carbon dioxide and fine particulate matter were monitored using a temperature and humidity meter, a noise meter, a carbon dioxide meter and a particulate counter, respectively. HRV parameters were measured using a 12-lead Holter. Mixed-effects models were used to evaluate the association between the TVOC and HRV parameters and establish the exposure-response relationships, and two-pollutant models were applied to examine the robustness of the results.
		                        		
		                        			RESULTS:
		                        			The mean age of the 50 female subjects was (22.5±2.3) years, and the mean body mass index was (20.4±1.9) kg/m2. During this study, the median (interquartile range) of indoor TVOC concentrations was 0.069 (0.046) mg/m3, the median (interquartile range) of indoor temperature, relative humidity, carbon dioxide concentration, noise level and fine particulate matter concentration were 24.3 (2.7) ℃, 38.5% (15.0%), 0.1% (0.1%), 52.7 (5.8) dB(A) and 10.3 (21.5) μg/m3, respectively. Short-term exposure to indoor TVOC was associated with significant changes in time-domain and frequency-domain HRV parameters, and the exposure metric for most HRV parameters with the most significant changes was 1 h-moving average. Along with a 0.01 mg/m3 increment in 1 h-moving average concentration of indoor TVOC, this study observed decreases of 1.89% (95%CI: -2.28%, -1.50%) in standard deviation of all normal to normal intervals (SDNN), 1.92% (95%CI: -2.32%, -1.51%) in standard deviation of average normal to normal intervals (SDANN), 0.64% (95%CI: -1.13%, -0.14%) in percentage of adjacent NN intervals differing by more than 50 ms (pNN50), 3.52% (95%CI: -4.30%, -2.74%) in total power (TP), 5.01% (95%CI: -6.21%, -3.79%) in very low frequency (VLF) power, and 4.36% (95%CI: -5.16%, -3.55%) in low frequency (LF) power. The exposure-response curves showed that indoor TVOC was negatively correlated with SDNN, SDANN, TP, and VLF when the concentration exceeded 0.1 mg/m3. The two-pollutant models indicated that the results were generally robust after controlling indoor noise and fine particulate matter.
		                        		
		                        			CONCLUSION
		                        			Short-term exposure to indoor TVOC was associated with significant negative changes in nocturnal HRV of young women. This study provides an important scientific basis for relevant prevention and control measures.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Young Adult
		                        			;
		                        		
		                        			Air Pollutants/analysis*
		                        			;
		                        		
		                        			Heart Rate/physiology*
		                        			;
		                        		
		                        			Volatile Organic Compounds/analysis*
		                        			;
		                        		
		                        			Carbon Dioxide
		                        			;
		                        		
		                        			Particulate Matter/adverse effects*
		                        			;
		                        		
		                        			Environmental Pollutants
		                        			
		                        		
		                        	
8.Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.
Yu-Jie WU ; Bo DENG ; Si-Bo WANG ; Rui QIAO ; Xi-Wen ZHANG ; Yuan LU ; Li WANG ; Shun-Zhong GU ; Yu-Qing ZHANG ; Kai-Qiao LI ; Zong-Liang YU ; Li-Xing WU ; Sheng-Biao ZHAO ; Shuang-Lin ZHOU ; Yang YANG ; Lian-Sheng WANG
Chinese journal of integrative medicine 2023;29(12):1059-1065
		                        		
		                        			BACKGROUND:
		                        			Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.
		                        		
		                        			OBJECTIVE:
		                        			This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.
		                        		
		                        			METHODS:
		                        			This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment.
		                        		
		                        			DISCUSSION
		                        			This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			ST Elevation Myocardial Infarction/therapy*
		                        			;
		                        		
		                        			Stroke Volume
		                        			;
		                        		
		                        			Ventricular Remodeling
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Microcirculation
		                        			;
		                        		
		                        			Ventricular Function, Left
		                        			;
		                        		
		                        			Myocardial Infarction/etiology*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Percutaneous Coronary Intervention/adverse effects*
		                        			;
		                        		
		                        			Heart Failure/drug therapy*
		                        			;
		                        		
		                        			Drugs, Chinese Herbal/therapeutic use*
		                        			;
		                        		
		                        			Randomized Controlled Trials as Topic
		                        			;
		                        		
		                        			Multicenter Studies as Topic
		                        			
		                        		
		                        	
9. In the Ascendant of Argon Biology
Jun WANG ; Peng-Fei CHENG ; Wen-Biao SHEN
Chinese Journal of Biochemistry and Molecular Biology 2023;39(7):905-910
		                        		
		                        			
		                        			 Argon is the most abundant inert gas in the atmosphere. For the past few years, the biological functions of argon have been discovered and gradually recognized by scientists. Argon, as a gaseous molecule with cytoprotective functions, could positively affect the physiological and pathological processes to varying degrees. Compared with the classic gasotransmitters, argon is non-toxic, harmless, and abundant, attracting extensive attention in all professions. This review outlined the biological effects and the potential molecular mechanisms of argon, and summarized the supply methods and the positive roles of argon in neuroprotection, cardiovascular disease, inflammatory disease, organ transplantation, and other animal clinical models, and also overviewed the research progress in post-harvest preservation of agricultural products and plant tolerance to abiotic stress. The mechanisms in the above studies about the biological effects of argon were closely related to argon control of receptors, ion channel proteins, reprogramming gene expression, and re-establishment of redox and ion homeostasis. Meanwhile, argon-regulated phosphorylation and dephosphorylation modification in enzyme proteins might be crucial in argon biology. The potential applications of argon have excellent prospects in medicine and agriculture with security and cost advantages. 
		                        		
		                        		
		                        		
		                        	
10.Invasive mucinous adenocarcinoma of the lungs versus mixed invasive mucinous and non-mucinous adenocarcinoma:a clinicopathological analysis
Shuangshuang PENG ; Wei LI ; Zhaoya ZHOU ; Biao ZHANG ; Chaoshan WANG ; Xiaohong PU ; Wen YANG ; Jun YANG ; Hongyan WU ; Yao FU ; Jieyu CHEN ; Xiangshan FAN
Chinese Journal of Clinical and Experimental Pathology 2023;39(11):1328-1333
		                        		
		                        			
		                        			Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0%)and 3(8.3%)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5%)(P<0.001)and 9 cases(52.9%)(P=0.001)were present in mIMA.There were 5 cases(13.9%)of high nuclear grade of IMA and 10 cases(58.8%)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5%in IMA,but 60.0%and 80.0%in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6%,21.9%,and 9.4%,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100%,20%,20%and 100%,6.7%,6.7%,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0%(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7%(5/12)and 33.3%(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4%)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1%)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.
		                        		
		                        		
		                        		
		                        	
            
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