The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance.

Diffuse large B-cell lymphoma (DLBCL) can be caused by multiple factors, including virus and autoimmune function, which in turn trigger persistent activation of the B-cell receptor (BCR) signaling pathway and other related signaling pathways, which collectively promote malignant B-cell proliferation and lead to tumor formation. Studies have shown significant progress in the treatment of primary and relapsed/refractory DLBCL with Bruton tyrosine kinase inhibitor (BTKi) in combination with chemotherapy, immunotherapy and small molecule inhibitors in the setting of poor outcome with BTKi monotherapy. This article reviews the progress of BTKi combined regimens in DLBCL.

Objective To analyze the fireworks signs of active pulmonary tuberculosis on CT, improve the understanding of CT findings of active pulmonary tuberculosis, and provide imaging basis for clinical treatment. Methods From January 2009 to December 2015, 26 patients (20 males, 6 females;age 16-72(39 ± 15) years old) with fireworks signs on CT were included, all patients had active pulmonary tuberculosis confirmed by sputum smear, bronchoalveolar lavage, biopsy or surgical specimen. A retrospective analysis of patient′s CT image data including the position, number, pattern of fireworks signs and other associated abnormalities were performed and the imaging features were summarized, pathological correlation with CT images was performed in patients with surgical or biopsy results. Results The fireworks signs on CT could be divided into three types:halo pattern, reversed halo pattern and homogenous pattern, which were 2, 7, 23 cases respectively in this study. Fireworks signs in 9 cases were located in unilateral lung field and 17 cases in bilateral lung field. Distribution of lesions was common bilaterally, mainly in the apical, posterior (apicoposterior) segments of the upper lobes and the superior segments of the lower lobes. Fireworks sign presented as a solitary lesion in 7 cases, 2 lesions in 3 cases, more than 3 lesions in 16 cases. Other pulmonary abnormalities included cavities, consolidation, tree-in-bud sign, pleural effusion, pleural thickening and mediastinal lymphadenopathy. Pathologically, fireworks sign corresponded to caseous granulomas in the bronchioles and alveoli. Conclusion Fireworks sign is one of CT signs of active pulmonary tuberculosis, which formed by the bronchial dissemination of tuberculosis on CT and the granulomas in bronchioles and alveoli on pathology.

Objective To find the invasion-associated clinical and CT risk factors of lung adenocarcinoma presenting as pure ground glass opacity nodule (pGGN) and to calculate odds ratio valve of each independent risk factor, the total risk value(TRV) of each lesion and an alert value for the management of pGGN. Methods From January 2014 to December 2016, 265 patients with 274 lesions pathologically confirmed lung adenocarcinoma with pGGN on CT who had undergone curative resection were included. Patient′s clinical data and CT features of pGGN were collected. CT features included the location, size, density and edge of pGGN, bubble-like sign, intrinsic abnormal air-bronchogram and vascular changes, tumor-lung interface. All lesions were divided into preinvasive groups (74 lesions) and invasive groups (200 lesions) according to the histopathology. Quantitative data were compared between preinvasive and invasive groups using t test or variance analysis (ANOVA) or nonparametric test. Qualitative data were compared between two groups using chi-square test. Logistic regression analysis was performed to evaluate the clinical and imaging independent risk factors of invasiveness. Receiver operating characteristics curve analysis was used to get the optimal cutoff value (alert value) for lesion invasiveness. Results There were statistically significant differences in patient age, lesion size, bubble-like sign, abnormal air-bronchogram, intrinsic vascular changes and tumor-lung interface between preinvasive and invasive groups (P<0.05). Logistic regression analysis showed that bubble-like sign, abnormal air-bronchogram, tumor-lung interface and lesion size were independent risk factors of invasiveness of pGGN, the OR value and 95％CI were 2.145(1.157—3.977), 3.167(1.211—8.281), 3.253(1.444—7.324), 1.175(1.061—1.303), respectively. The ROC curve demonstrated the optimal cutoff of TRV for predicting invasiveness was 3.5 with the sensitivity of 85.5％and specificity of 69.0％. Conclusions TRV can predict the invasiveness of pGGN. Surgical treatment is recommended if TRV is≥3.5.

Objective To analyze the data on the pathogenic bacteria responsible for infected pan creatic necrosis (IPN) and drug resistance,and to study the impact on prognosis of patients.Methods The clinical data from 101 patients who were diagnosed to have IPN in the Xuanwu Hospital of the Capital Medical University,Beijing,from January 2011 to August 2017,were analyzed retrospectively.Logistic regression and statistical analysis were performed to evaluate the species composition and drug-resistance in the pathogens obtained from the pancreatic necrosis tissues or the drainage culture fluids from these IPN patients in the first,second or third surgery.Results Among the 101 patients,80 had bacteria-positive cultures,of which 97 were pathogenic bacteria:74.2％ were Gram-negative,22.7％ were Gram-positive,and 3.1％ were fungi.The commonest bacterial strains included Escherichia coli (n =20),Klebsiella pneumonia (n =17),Pseudomonas aeruginosa (n =13),Acinetobacter baumannii (n =11),and Enterococcus (hereafter called Ent.) faecium (n =11).Drug resistance analysis showed that the Gram-negative bacilli were susceptible to carbapenems.The resistance rates for all the antibiotic types in K.pneumoniae exceeded 50％.The use of enzyme inhibitors significantly improved bacterial sensitivity to the beta-lactams.The Gram-positive bacteria were sensitive to vancomycin and tigecycline.Drug-resistant fungi were not identified.The multidrug resistance rates for E.coli,K.pneumoniae,P.aeruginosa and A.baumannii Gram-negative bacilli were 35.0％ (7/20),76.5％ (13/17),53.9％ (7/13) and 63.6％ (7/11),respectively,while that for Gram-positive Ent.faecium was 75.0％ (9/12).Forty patients underwent three or more surgeries.Regression analysis showed that the proportion of patients with severe acute pancreatitis who underwent three or more surgeries was higher than that of the patients who underwent fewer surgeries.However,neither the number of overall infections,nor the number of infections with multiple drug-resistant pathogens,was associated with the number of operations.Conclusions Gram-negative bacilli was mainly involved in the primary infections of patients with IPN.E.coli was the most common microbe.Our clinical experience showed that enzyme penicillins or carbapenems were the preferred treatment options.

Objective To observe the outcomes of no necrotic cavity lavage after debridement and drainage in patients with infected pancreatic necrosis (IPN).Methods From February 2014 to August 2017,there were 89 patients who were diagnosed as IPN undergoing minimally invasive surgery with no necrotic cavity lavage and large caliber-wide channel drainage in Department of General Surgery,Xuanwu Hospital,Capital Medical University.There were 57 male and 32 female patients aging of (49.5± 14.4)years (ranging from 23 to 84 years).The body mass index of 89 patients was (25.4± 3.8) kg/m2 (ranging from 17.6 to 36.7 kg/m2).Among the 89 patients,37 cases(41.6％) of biliary pancreatitis,10 cases (11.2％) of alcoholic pancreatitis,16 cases (18.0％) of hyperlipidemic pancreatitis,and 26 cases (29.2％) of other reasons.Results Of 89 patients,IPN in 6 patients (6.7％) resolved using only percutaneous catheter drainage;another 83 patients underwent laparoscopic debridement (n =3,3.4％) or video-assisted debridement (n =80,89.9％).No patient was conversed to laparotomy.The average operation frequency and surgery time was (2.3±1.7) times and (56.5±31.7) minutes.The median bleeding volume and total length of stay was 10(0-600) ml and 34(6-172) days separately.The complication rate(Clavien-Dindo grade ≥Ⅲ) was 9.0％ (8/89) which involved mainly abdominal hemorrhage (5/8) and digestive tract fistula formation (3/8).The overall mortality rate was 6.7％ (6/89).Among them,3 cases died of abdominal infection,bacteremia and multiple organ failure,2 cases died of pulmonary infection and bacteremia and 1 case died of fungal infection.Conclusion No necrotic cavity lavage after debridement and drainage operation is considered effective and safe for IPN patients.

Objective To observe the outcomes of no necrotic cavity lavage after debridement and drainage in patients with infected pancreatic necrosis (IPN).Methods From February 2014 to August 2017,there were 89 patients who were diagnosed as IPN undergoing minimally invasive surgery with no necrotic cavity lavage and large caliber-wide channel drainage in Department of General Surgery,Xuanwu Hospital,Capital Medical University.There were 57 male and 32 female patients aging of (49.5± 14.4)years (ranging from 23 to 84 years).The body mass index of 89 patients was (25.4± 3.8) kg/m2 (ranging from 17.6 to 36.7 kg/m2).Among the 89 patients,37 cases(41.6％) of biliary pancreatitis,10 cases (11.2％) of alcoholic pancreatitis,16 cases (18.0％) of hyperlipidemic pancreatitis,and 26 cases (29.2％) of other reasons.Results Of 89 patients,IPN in 6 patients (6.7％) resolved using only percutaneous catheter drainage;another 83 patients underwent laparoscopic debridement (n =3,3.4％) or video-assisted debridement (n =80,89.9％).No patient was conversed to laparotomy.The average operation frequency and surgery time was (2.3±1.7) times and (56.5±31.7) minutes.The median bleeding volume and total length of stay was 10(0-600) ml and 34(6-172) days separately.The complication rate(Clavien-Dindo grade ≥Ⅲ) was 9.0％ (8/89) which involved mainly abdominal hemorrhage (5/8) and digestive tract fistula formation (3/8).The overall mortality rate was 6.7％ (6/89).Among them,3 cases died of abdominal infection,bacteremia and multiple organ failure,2 cases died of pulmonary infection and bacteremia and 1 case died of fungal infection.Conclusion No necrotic cavity lavage after debridement and drainage operation is considered effective and safe for IPN patients.

Objective To analyze the value of abnormal air bronchogram for predicting the invasiveness of lung adenocarcinoma with pure ground-glass nodule (pGGN).Methods From April 2014 to February 2016,157 patients with 165 pGGN lung adenocarcinomas confirmed by surgical pathology were selected.There were 30 pre-invasive lesions (AAH+AIS),39 minimally invasive adenocarcinoma (MIA),and 96 invasive adenocarcinoma (IAC).CT characteristics including lesion size,density,abnormal air bronchogram were recorded.All lesions were divided into two groups:normal group (no air bronchogram or normal air bronchogram) and abnormal air bronchogram group.Chi-square test was used to analyze the difference of pathological subtypes between the two groups.Mann-Whitney rank test was used to analyze the size difference of pGGN between the two groups.Two-independent samples t-test was used to analyze the lesion density difference of pGGN between the two groups.Results Of the 165 lesions,85 were found to have air bronchogram,there were 12 lesions in 30 pre-invasive lesions (AAH+AIS),17 in 39 MIAs,56 in 96 IACs.Abnormal air bronchogram were demonstrated in 61 lesions which was 1 in 30 pre-invasive lesions (IACs+AIS),13 in 39 MIAs and 47 in 96 IACs,significant differences were found between two groups (x2=25.943,P＜0.01).The mean size of the IACs were (10.8±4.2) mm for normal group,(17.0±6.7) mm for abnormal air bronchogram group,the mean density were (-519± 118) HU and (-518± 124) HU,respectively.There was a significant difference in lesion diameter between two groups (Z=-6.197,P＜0.01),but not in density (t=-0.042,P=-0.966).Conclusions Abnormal air bronchogram can be used to predict the invasiveness of pGGN lung adenocarcinoma,and is correlated with lesion size,but not with density.

Objective To observe the influence on the sensitivity of pancreatic cancer cell line BxPC-3 to gemcitabine of silencing PAUF gene.Methods BxPC-3 cells,which overexpress PAUF,was stably transfected with PAUF-shCtrl and PAUF-shRNA to establish BxPC-3_shCtrl and BxPC-3_shPAUF cells as control and experiment group.Then the mRNA and protein expression level of PAUF in these two cell lines were detected by RT-PCR and western blot,respectively.The growth inhibition rates of these two cell lines treated with different concentrations of gemcitabine (0,3.1,6.25,12.5,25,50,100,200 nmol/L) were detected by MTT.Apoptosis rates in the cells treated with different concentrations of gemcitabine (0,75,100 nmol/L) were then observed by flow cytometry.Results The relative PAUF mRNA expression level in BxPC-3_shCtrl and BxPC-3 cells were 1.00 ± 0.06 and 0.83 ± 0.07,which were significantly high er than that in BxPC-3_shPAUF cells (0.25 ± 0.02;both P ＜ 0.05).The relative PAUF protein expression level in BxPC-3_shCtrl and BxPC-3 cells were 0.89 ± 0.07 and 0.95 ± 0.04,which were significantly high er than that in BxPC-3_shPAUF cells (0.31 ± 0.03;both P ＜ 0.05).The IC50 value of gemcitabine to BxPC-3_shCtrl cell was (22.88 ± 2.43) nmol/L,which was significantly higher than that of BxPC-3_shPAUF cells [(1.06 ± 0.02) nmol/L;P ＜ 0.05];apoptosis rate of BxPC-3_shPAUF cells treated by gemcitabine increased faster than that of BxPC-3_shCtrl cells.Conclusion PAUF silencing could greatly enhance the sensitivity of BxPC-3 cells to gemcitabine.

PurposeTo discuss the imaging features of multi-slice spiral CT (MSCT) and PET/CT in lymphoma with pulmonary lesions as the initial presentation.Materials and Methods Eighteen cases of lymphoma with pulmonary lesions as initial presentation confirmed by operation and pathology were retrospectively analyzed including Hodgkin lymphoma (HL) in 3 cases and non-Hodgkin lymphoma (NHL) in 15 cases. All 18 patients underwent MSCT, of which 11 also underwent PET/CT. The MSCT manifestations included number of lesions, morphology, density and bronchial change. PET/CT evaluated lesions in other body parts and SUVmax of lung lesions.Results MSCT showed single lung lesion in 6 cases, multiple lung lesions in 12 cases. Masses were seen in 9 cases, non-masses in 7 cases, and mixed type in 2 cases. There was single consolidation in 3 cases and mixed consolidation in 15 cases. Air bronchogram was identified in 15 cases. CT predictive diagnosis was lymphoma in 3 cases, lung cancer in 5 cases, pneumonia in 7 cases, granuloma in 1 patient, and indeterminate in 2 cases. PET/CT showed hypermetabolic lung lesions in 11 patients, mediastinal lymph node in 3 cases, and unilateral supraclavicular lymphadenopathy in 1 case. One patient showed pancreatic tail masses, gastric wall thickening and haunch masses. All 11 patients were diagnosed as malignant tumor, of which 8 cases as lymphoma.Conclusion MSCT manifestations of lymphoma with pulmonary lesions as initial presentation include multiple lesions, polymorphic type and heterogeneity with air bronchogram. PET/CT has better accuracy than MSCT.