OBJECTIVETo analyze the clinicopathological characteristics of patients with anaplastic lymphoma kinase (ALK) rearrangements in lung adenocarcinoma, and the clinical therapy and prognosis of the patients.

METHODSClinicopathological data of 34 cases of ALK-positive patients treated in the Beijing Chest Hospital from 2005 to 2014 were reviewed. The expression of ALK proteins in the resected tumors was detected by immunohistochemistry, and EGFR mutations were examined by polymerase chain reaction and a direct DNA sequencing method.

RESULTSAmong the 34 patients, 20 were male and 14 were female, the median age was 49, and 11 were smokers and 23 were never smokers. The clinical stages of the patients were stage IA in 5 patients, IB in one patient, IIA in two patients, IIIA in 16 patients, IIIB in 5 patients, IV in 4 patients, and one patient of unknown stage. ALK-positive tumors showed strong granular staining in cell cytoplasm by immunohistochemistry. Forteen patients were solid predominant subtype with mucin production, 10 of acinar predominant subtype, 6 of papillary predominant subtype, 3 of micropapillary predominant subtype, and one was of colloid variant. There were 18 cases with mucin production, 6 cases had signet-ring cell morphology, and 10 cases showed cribriform pattern. Only one patient had coexistence of ALK rearrangement and EGFR mutation (L858R at exon 21). Of the 34 patients, 24 patients were followed up. The median follow up of the 24 patients was 11.0 months (1.7-48.7 months).

CONCLUSIONSALK-positive tumors as a molecular subtype of lung adenocarcinoma have distinct clinicopathological features. The histological findings of ALK-positive tumors are characterized by solid predominant subtype with mucin production, acinar predominant subtype, signet-ring cells and cribriform structures. They were rarely co-mutated with EGFR mutation.

Adenocarcinoma ; enzymology ; pathology ; therapy ; Exons ; Female ; Gene Rearrangement ; Genes, erbB-1 ; Humans ; Immunohistochemistry ; Lung Neoplasms ; enzymology ; pathology ; therapy ; Male ; Middle Aged ; Mucins ; biosynthesis ; Mutation ; Neoplasm Proteins ; genetics ; Polymerase Chain Reaction ; Prognosis ; Receptor Protein-Tyrosine Kinases ; genetics ; Sequence Analysis, DNA

Objective:To establish the long-term trajectories of lung function in children with bronchial asthma (asthma) and explore the risk factors of persistent pulmonary dysfunction.Methods:A retrospective cohort study was conducted.Children with asthma aged above 14 years who had been followed up regularly and completed pulmonary function testing in Children′s Hospital of Capital Institute of Pediatrics were enrolled in the study from January to December 2019.Their lung function data and clinical information were collected.The latent class growth model (LCGM) was used to fit the change of lung function in children with asthma, and different trajectory groups were established.Comparison between groups was performed by t-test, ANOVA or Chi- square test.The risk factors for the lung function trajectory were analyzed by the multivariate Logistic regression method. Results:A total of 173 children with asthma, aged from 6 to 17, were enrolled, and 1 160 lung function tests were completed.Four forced expiratory volume in the first second/forced vital capacity (FEV 1/FVC) latent class trajectory groups were established, including persistent high level [27 cases (15.6%)], above average level [66 cases (38.1%)], below average level [66 cases (38.1%)], and persistent low level [14 cases (8.1%)]. In all the 4 different trajectory groups, the FEV 1/FVC values were significantly different among patients of different ages (all P<0.05). The FEV 1/FVC values of patients at all ages in the persistent high level group were above 90%.The FEV 1/FVC values of patients in other 3 level groups decreased as a whole as the age increased.FEV 1/FVC of patients in the persistent low level group decreased to below 80% when they entered the school age period and approached 70% in adolescence.The trajectory and fluctuation of maximal midexpiratory flow (MMEF), which represents the small airway function, were similar to those of FEV 1/FVC.Risk factor analysis showed that the risk of lung function decreasing below the average level in children with typical asthma was 11.940 times higher than that in children with cough variant asthma ( P=0.008). The risk of lung function deteriorating to below the average level in children with multiple allergen sensitivities was 7.462 times higher than that in children with single allergen sensitivity ( P=0.015). Children taking drugs irregularly were 6.337 times more likely to suffer persistent low lung function than children taking drugs regularly ( P=0.035). Boys were 6.186 times more likely to suffer a lung function reduction to below the average level than girls ( P=0.002). Conclusions:Four long-term trajectories of lung function in asthmatic children aged 6 to 17 years can be established: persistent high level, above average level, below average level and persistent low level.The long-term lung function of nearly a half of the asthmatic children is below the average level.Many children develop persistent airflow limitation in adolescence, and few at school age.Typical asthma, multiple allergen sensitivities, irregular medication and boy were the risk factors of long-term lung function reduction.

Background: Expression of microRNA⁃320 (miR⁃320) is down regulated in acute pancreatitis, and the mechanism of its effect on acute pancreatitis is still unclear. Aims: To investigate the effect of miR⁃320 on intestinal injury in rats with acute pancreatitis and its mechanism. Methods: Rats were randomly divided into sham operation group, model group, miR⁃ 320 agonist group (agomir miR ⁃ 320 group), miR ⁃ 320 agonist control group (agomir NC group), JAK2 inhibitor group (AG490 group), and NF⁃κB pathway inhibitor group (PDTC group). The rat model of acute pancreatitis was established by retrograde injection of 5% sodium taurocholate to the bile duct. The automatic biochemical analyzer was used to detect serum levels of amylase and lipase; ELISA assay was used to detect serum levels of TNF⁃α and IL⁃1β; HE staining was used to observe the pathological changes of rat pancreas and ileum; TUNEL staining was used to observe cell apoptosis in rat ileum; real⁃time fluorescent quantitative PCR (RT⁃qPCR) was used to detect the expression of miR⁃320 in ileum tissue; Western blotting method was used to detect the expressions of JAK2/STAT3 and NF⁃κB signaling pathway related proteins in ileum. Results: Compared with sham operation group, the pancreas and ileum were severely injured in model group, and the pathological score and ileum cell apoptosis were significantly increased (P<0.05), serum levels of amylase, lipase, TNF⁃ α, and IL⁃1β were significantly increased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly decreased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly increased (P<0.05). Compared with model group, the pathological damages of pancreas and ileum in agomir miR ⁃ 320 group, AG490 group and PDTC group were reduced, and the pathological score and ileum cell apoptosis were significantly decreased (P<0.05), serum levels of amylase, lipase, TNF ⁃ α, and IL ⁃ 1β were significantly decreased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly increased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃ p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly decreased (P<0.05). Conclusions: MiR⁃320 can improve the intestinal injury in rats with acute pancreatitis by inhibiting the activation of JAK2/STAT3 and NF⁃κB signaling pathways.

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.