Objective:To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor.Methods:Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed.Results:Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively.Conclusions:SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Purpose To investigate the consistency of the"Standards and guidelines for the interpretation and reporting of sequence variants in cancer"published in 2017 by the Associa-tion for Molecular Pathology(AMP)/American Society of Clini-cal Oncology(ASCO)/College of American Pathologists(CAP).Methods Sixty variants of 26 genes from 11 types of cancer were selected.5 professionals from four hospitals e-quipped with in-hospital NGS detection ability were used to in-terpret the treatment,diagnosis and progenosis respectivly.In the first phase of the study,each researcher rated the variants individually according to their own understanding of the 2017 guideline.In the second phase,the details of the guidelines'e-valuation principles were discussed and interpreted again after reaching a consensus.Results Eleven principles recognized by all participants were summarized as a supplement to interpreta-tion.Fleiss consistency showed that the consistency of interpre-tation of treatment and prognostic significance in the second stage was higher than that in the first phase(κ value was 0.166 vs 0.276,0.014 vs 0.185).The consistency of interpretation of diagnostic significance in the second stage was lower than that in the first phase(κ value was 0.454 vs 0.035).Conclusion There is inconsistency in the clinical interpretation of tumor gene variation among different laboratories.It is feasible for laborato-ries to establish a mutually recognized interpretation system for the clinical diagnosis,treatment,and prognosis of tumors.

Objective:To explore the value of early pulmonary function tests in children with community acquired pneumonia(CAP)by analyzing the clinical and imaging manifestations and pulmonary function tests of children with CAP.Methods:The clinical data of children diagnosed with CAP and undergoing routine pulmonary ventilation tests within 24 hours of admission were retrospectively collected from January 2016 to June 2018 in the Department of Pediatric Respiratory Medicine of Shengjing Hospital Affiliated to China Medical University.The children′s pulmonary ventilation function test data were statistically analyzed with clinical manifestations, laboratory tests and imaging data.Results:A total of 154 children were included in the study, of which 54(35.06%)had normal pulmonary ventilation function, and the remaining 100 children(64.94%)had different degrees of pulmonary ventilation impairment, which were manifested as restrictive ventilation disorder in 54 cases(35.06%), obstructive ventilation disorder in 8 cases(5.19%), mixed ventilation disorder in 30 cases(19.48%), and small airway ventilation dysfunction in 8 cases(5.19%). According to the results of pulmonary ventilation function, the mixed ventilation dysfunction group had a greater probability of pulmonary imaging changes to consolidation than the normal group( χ2=7.83, P=0.007). Mycoplasma pneumoniae infection was negatively correlated with forced expiratory volume in the first second, 75% forced expiratory flow, one second rate and maximal mid-expiratory flow level( r=-0.23, r=-0.22, r=-0.25, r=-0.23, all P<0.05), and there was no significant correlation with the level of forced vital capacity. Conclusion:Early pulmonary ventilation test has important clinical significance in the diagnosis and treatment of CAP in children.

Sleep disorder is common in patients with asthma, especially in patients with severe asthma.Sleep disorder correlates with poor asthma control and poor quality of life.Sleep disorder in asthmatic patients may be related to the circadian variation in airway physiology and airway inflammation, but may also be related to specific sleep disorders such as obstructive sleep apnea(OSA), gastroesophageal reflux, obesity, psychological problems, etc.OSA is an independent risk factor for poor asthma control.At the same time, asthma will aggravate OSA.Treatment of OSA with continuous positive airway pressure(CPAP)may lead to improved asthma-specific quality of life.

Objective:To summarize the clinical characteristics of plastic bronchitis caused by severe mycoplasma pneumoniae pneumonia in children, to find the risk factors for plastic bronchitis, and to provide references for judging the prognosis and comprehensively formulating treatment plans.Methods:We retrospectively analyzed the clinical data(146 cases)of children with severe mycoplasma pneumoniae pneumonia who underwent bronchoscopy in the Department of Pediatric Respiratory Medicine of Shengjing Hospital of China Medical University from January 2017 to December 2019.According to whether it was plastic bronchitis, all patients were divided into plastic bronchitis group(68 cases) and non-plastic bronchitis group(78 cases), and the gender, age, laboratory examination indicators, imaging characteristics and treatment of children were collected under the circumstances.The single factor with clinical significance and statistical significance would be subjected to multivariate Logistic regression analysis.Results:There were no significant differences in gender, age, heat duration, white blood cell count, C-reactive protein value, and interleukin-6 value between the two groups(all P>0.05). The percentage of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, D-dimer, number of cases of pleural effusion, length of hospital stay, and number of endoscopy in the plastic bronchitis group were higher than those in non-plastic bronchitis group, the number of right upper lobe consolidation cases was less than that in the non-plastic bronchitis group, and the differences were statistically significant( P<0.05). Multiple Logistic regression analysis showed that pleural effusion( OR=4.898, 95% CI 2.195-10.926) and lactate dehydrogenase ( OR=1.051, 95% CI 1.003-1.101) were independent predictors of plastic bronchitis in children with severe mycoplasma pneumoniae pneumonia. Conclusion:For children with severe mycoplasma pneumoniae pneumonia, if lung CT shows that the upper lobe of the non-right lung is uniformly compacted and complicated with pleural effusion, lactate dehydrogenase is significantly increased, and attention should be paid to the possibility of plastic bronchitis.Timely improvement of fiberoptic bronchoscopy may shorten the course of the disease and reduce the occurrence of complications.

Objective:To investigate MAML2 gene rearrangement, gene fusion patterns, and the clinicopathological characteristics of primary pulmonary mucoepidermoid carcinoma (PMEC).Methods:Forty-six cases of primary PMEC from Fudan University Zhongshan Hospital and Fudan University Shanghai Cancer Center between 2017 and 2020 were collected. MAML2 gene rearrangement in all cases was detected by fluorescence in situ hybridization (FISH). In 20 cases, MAML2 fusion patterns were detected by targeted RNA sequencing (RNAseq). The relationship between MAML2 gene rearrangement, fusion patterns, clinicopathological characteristics, and prognosis was analyzed.Results:The average age of PMEC patients was 41 years (range 15-71 years); the ratio of male to female was about 1.1 ∶ 1.0. Most PMECs were low grade in histopathology with an early clinical stage (stageⅠ-Ⅱ).The overall positive rate of MAML2 gene rearrangement detected by FISH was about 80.4% (37/46), and the rate was higher in low-grade PMEC (91.7%, 33/36). Of the 20 cases detected by RNAseq, all the 19 FISH positive cases showed gene fusion, mainly CRTC1-MAML2 fusion (16/19), the other three cases showed CRTC3-MAML2 fusion (3/19), the break point of all the fusion patterns was CRTC1/3 (exon 1)-MAML2 (exon 2); No gene fusion was detected in the single FISH negative case; Compared with the MAML2 FISH negative patients, the PMECs carrying CRTC1-MAML2 fusion were more commonly found in patients age ≤ 40 years, maximum tumor diameter ≤ 2 cm, low histopathological grade and early clinical stage (all P<0.05); The three PMECs carrying CRTC3-MAML2 fusion gene were all female with early clinical stage; Univariate analysis showed that MAML2 gene rearrangement/fusion, onset age ≤ 40 years old, smaller tumor size, low histopathological grade, early clinical stage, no metastasis at diagnosis and surgical treatment were significantly correlated with overall survival ( P<0.05), but Cox regression analysis suggested that none of the above indicators were the independent prognostic factors for the survival of PMEC. Conclusions:The high incidence of MAML2 gene rearrangement in PMEC suggests that it is an important molecular diagnostic marker of PMEC. RNAseq confirms that CRTC1/3-MAML2 is the main fusion pattern in PMEC, suggesting that MAML2 fusion transcription may be an important driving factor of PMEC. MAML2 rearrangement/fusion and related clinicopathological characteristics are associated with good prognosis.

Objective:To explore the clinical characteristics of children with atopic mycoplasma pneumoniae pneumonia and to provide evidence for the diagnosis and treatment of children with atopic mycoplasma pneumoniae pneumonia.Methods:One hundred and eighty cases of children diagnosed with mycoplasma pneumoniae pneumonia in Shengjing Hospital of China Medical University from January 2018 to December 2018 were selected. According to whether they had atopic constitution, they were divided into atopic mycoplasma pneumoniae pneumonia(AMPP)group(84 cases)and non-atopic mycoplasma pneumoniae pneumonia(NAMPP)group(96 cases). The clinical data of age, sex, fever time, hospital stay, application time of macrolides, white blood cells, CRP, LDH, and lung CT were collected from the two groups, and the differences in clinical manifestations, laboratory examinations and imaging manifestations of the two groups were analyzed retrospectively.Results:(1)Both the absolute value of eosinophils and total IgE values in the AMPP group were higher than those in the NAMPP group, and the difference was statistically significant( P<0.05). The incidence of severe mycoplasma pneumoniae pneumonia(SMPP)and/or refractory mycoplasma pneumoniae pneumonia(RMPP)and chest imaging manifestations of interstitial pneumonia in the AMPP group was higher, and the difference was statistically significant( P<0.05). (2)The incidence of wheezing in the AMPP group was 48.81%(41 cases/84 cases), which was significantly higher than that in the NAMPP group 22.92%(22 cases/96 cases). The duration of cough and wheezing in the AMPP group was longer than that in the NAMPP group( P<0.05), with statistically significant differences( P<0.05). (3)In the AMPP group, 36.90%(31 cases /84 cases)of the children received intravenous methylprednisolone treatment, which was significantly higher than the 20.83%(20cases /96 cases)of the NAMPP group. Lung rales absorption time in the AMPP group[(9.73±3.59)d] was significantly longer than that in the NAMPP group[(7.52±2.44)d], and the difference was statistically significant( P<0.05). Lung CT examination showed that the absorption of lung inflammation in the AMPP group was worse than that in the NAMPP group, with a statistically significant difference( P<0.05). The hospitalization time of children in the AMPP group[(10.88±4.17)d] was longer than that in the NAMPP group[(9.68±2.68)d], with a statistically significant difference( P<0.05). Conclusion:The condition of AMPP is more serious than that of NAMPP, and it is more likely to cause incomplete absorption of pulmonary inflammation.

Objective To explore the effect of grape seed proanthocyanidin extract(GSPE) on the proliferation of airway smooth muscle cells( ASMCs) induced by platelet-derived growth factor( PDGF) and the underlying molecular mechanism. Methods ASMCs of primary rat were cultured. MTT and flow cytom-etry were used to detect the cell proliferation activity and cell cycle distribution of ASMCs which were treated with PDGF and GSPE respectively. The expression levels of cyclin D1,extracellular regulated protein kinases ( ERK)1/2,p-ERK1/2 and β-actin protein in each group ASMCs were analyzed using western blotting assay after ERK1/2 inhibitor PD98059 intervention. Results Compared with control group,cell proliferative activ-ity,S phase fraction and the expression of cyclin D1 and p-ERK1/2 protein increased in PDGF induced group (P<0. 05). These effects induced by PDGF could be reversed by GSPE. PD98059 also could block PDGF induced higher expression of p-ERK1/2 and cyclin D1 proteins in rat ASMCs. Conclusion GSPE can inhib-it PDGF induced cell proliferation and via ERK1/2 signaling pathway in rat ASMCs,which provide a new way for treatment of bronchial asthma.

Objective Allergic asthma is a chronic inflammatory disease of the airways.T lymphocytes play important roles in the pathogenesis of asthma.The voltage-gated Kvl.3 potassium channel may be a key factor in the activation of T lymphocytes.This research aims to detect the function of Kvl.3 channel in the neutrophlial asthma(NA) model and eosinophilic asthma(EA) model.Methods A total of 24 mice were randomly assigned into three groups:control,neutrophilic asthma model and eosinophilic asthma group.Neutrophilic asthma model was established with ovalbumin (OVA)and lipopolysaccharide(LPS);eosinophilic asthma was established with OVA and Al(OH)3;airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument;lung inflammation changes were observed by pathological HE staining;IL-17A and IL-4 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA;Kvl.3 channel protein level in lung was evaluated by western blot;the change of current density in CD4 +.T lymphocytes were tested by whole-cell patch clamp technique.Results Levels of IL-17A and IL-4 in bronchoalveolar lavage fluid increased in both NA and EA model (P ＜ 0.05).Compare with EA model,the IL-17A level was significantly higer in NA model,while the IL-4 level was significantly lower.In NA and EA model,kv1.3 protein expression in lung tissue was significantly higher than that in the control group(P ＜ 0.05),and kv1.3 protein expression in NA model was significantly higer than that in the EA model (P ＜ 0.05).Current intensity and current density of kv1.3 channel increased in both NA and EA model.While the current intensity and current density of kv1.3 channel were significantly higher in NA model than that in EA model.Conclusion Kv1.3 protein level,Kv1.3 channel current intensity and kv1.3 channel current density increased in both NA and EA model,especially in NA group,providing a new way for treatment of bronchial asthma.

Objective To explore effect of grape seed proanthocyanidin extract (GSPE)on airway inflammation and hyperresponsiveness of ovalbumin-induced murine asthma model and the associated regulatory effect on Treg/Th17 imbalance.Methods A total of 40 mice were randomly assigned to four experimental groups:control,asthma model,low dose GSPE (40 mg/kg),and high dose GSPE (80 mg/kg).Acute asthma model was established with OVA;airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument;lung inflammation changes were observed by pathological HE staining;Treg/Th17 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA;the expressions of forkhead/winged helix transcription factor(Foxp3) mRNA and retinoid-related orphan receptor gammat (RORγt) mRNA in lung tissue of each group were gained by Real-time PCR method.Results GSPE inhibited ovalbumin-induced increases in airway responsiveness(P ＜ 0.05).Histological studies demonstrated that GSPE substantially inhibited OVA-induced airway inflammation in lung tissue.GSPE decreased IL-17A levels and increased IL-10 levels in bronchoalveolar lavage fluid (P ＜ 0.05).In the asthma model group,RORγt mRNA expression in lung tissue was significantly higher than that in the control group(P ＜ 0.05)and Foxp3 mRNA expression was significantly lower than that in the control group (P ＜ 0.05).In the GSPE group,RORγt mRNA expression was lower than that in asthma model group (P ＜ 0.05),however the Foxp3 mRNA expression was higher than that in asthma model group(P ＜ 0.05).Conclusion GSPE could alleviate airway hyperresponsiveness and airway inflammation of in asthmatic mice.It can modify the asthmatic mice Treg/Th17 imbalance by decreasing IL-17A and increasing IL-10 concentration at the level of cytokines;and also by increasing Foxp3 mRNA expression and inhibiting the expression of RORγt mRNA at the transcriptional level,which provide a new way for treatment of bronchial asthma.