Ten autopsy cases of bronchiole-alveolar carcinoma (BAC) were reported. Grossly, BAC may be divided into 3 types, i. e. finely nodular, coarsely nodular and diffuse type. Histologic pattern falls into 2 categories: ' (1) alveolar type, (2) papillary type. Metastasis is most frequently mediated through lymphatics, spreading to the regional lymph nodes. Next, they are spread by blood stream. Brain (meningeal carcinomatosis),bone and adrenal glands are the frequent metastasized sites. Pulmonary fibrosis and scar formation seem to be the predisposing factors to BAC.

Objective To evaluate the effect of Chinese gentian extracts on the proliferation of,apoptosis and phosphorylation of epidermal growth factor receptor (EGFR) in HaCaT cells induced by epidermal growth factor (EGF).Methods Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate the proliferation of HaCaT cells pretreated with EGF of 20 μg/L for 24 hours followed by 24 hours of treatment with various concentrations of Chinese gentian extracts.Flow cytometry was carried out to detect apoptosis in HaCaT cells pretreated with EGF of 20 μg/L for 24 hours followed by 4 hours of treatment with different concentrations of Chinese gentian extracts.Western blot was conducted to measure the level of phosphorylated EGFR in HaCaT cells treated with different concentrations of Chinese gentian extracts for 24 hours followed by treatment with EGF of 20 μg/L for 10 minutes.Results Chinese gentian extracts inhibited the proliferation (r =-0.991,P ＜ 0.01),but promoted the apoptosis (r =0.996,P ＜ 0.05) of HaCaT cells induced by EGF in a dose-dependent manner.At the same time,the extracts suppressed the phosphorylation of EGFR in HaCaT cells induced by EGF,and the suppressing effect increased with the rise in the concentration of the extracts.Conclusions Chinese gentian may inhibit the proliferation,but promote the apoptosis of keratinocytes by decreasing EGFR phosphorylation and blocking relevant intracellular signaling pathways.

Objective To determine the role and mechanism of peroxisome proliferator activated receptors (PPAR) α in a mouse model of D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced acute liver failure(ALF).Methods Firstly,C57BL/6 mice were randomly divided into control group(n =8),ALF 2h group(n =8),ALF 4h group (n =8),ALF 6h group (n =8).Secondly C57BL/6 mice were randomly divided into control group(n =8),ALF group(n =8),WY14643 group(n =8).To induce ALF,the mice were injected intraperitoneally with D-GalN (700 mg/kg) and LPS (10 μg/kg).WY14643 (6 mg/kg),the selective agonist of PPAR α,was administered via tail vein two hours prior to D-GalN/LPS exposure.Two,four,and six hours after D-GalN/LPS treatment in the first study,mice were anesthetized and blood was collected,6h after D-GalN/LPS treatment in the second study,blood was collected.The liver tissue was harvested for histology and mRNA extraction.Serum levels of ALT and AST were measured to evaluate the hepatic damage.Inflammatory cytokines (TNFα,IL-1β,IL-6) and chemokines (CXCL-1,CXCL-10) were detected by real-time quantitative PCR.Differential protein expression of p-NF-κBp65,p-JNK,p-ERK,p-p38 in inflammatory pathways was detected by Western blotting.Significance of inter-group differences was assessed by one-way ANOVA,and pairwise comparison was performed by the least significant difference test.Results The gene and protein expression of PPAR α were gradually reduced during the development of ALF.Compared with the model group,the liver architecture was better preserved almost with normal morphology in WY14643-treated mice.Serum ALT and AST levels in WY14643-treated group were significantly lower [ALT:(555 ±62)U/L vs (2 898 ±822) U/L,P ＜0.05; AST:(791 ±58) U/L vs (3 013 ±997)U/L,P ＜ 0.05].The expression of proinflammatory cytokines and chemokines was significantly suppressed during the activation of PPAR α.In the second study,the levels of gene expression of proinflammatory cytokines and chemokines were detected in control group,ALF group and WY14643 group respectively as followings:TNFα (0.161 ± 0.085,7.996 ± 1.068,3.346 ± 0.94,P ＜ 0.05),IL-1β(0.041 ±0.002,3.657 ±0.904,0.176±0.089,P＜0.01),IL-6 (0.018 ±0.008,1.762 ±0.589,0.163±0.0487,P ＜0.05),CXCL-1 (0.063 ±0.008,7.881 ±0.966,2.737 ±0.864,P ＜0.01),CXCL-10 (0.054 ±0.005,5.671 ±0.948,2.578 ±0.804,P ＜0.05).Conclusion Our findings first demonstrate that PPARα protects liver from injury in an ALF mouse model by suppressing inflammatory response,indicating PPARα as a potential new therapeutic target for ALF.

Objective To observe the clinical efficacy of fire-needle therapy in treating scapulohumeral periarthritis, and to observe the changes of pain score and the motor function of shoulder joint. Method Totally 180 patients were randomized into a fire-needle therapy group of 90 cases and a filiform needle group of 90 cases by randomized single-blinded method. Result There were significant differences between the two groups in comparing the recovery rate, motor function of shoulder joint, and the relapse rate 30 d after the whole intervention (P<0.01), while there were no significant differences in Visual Analogue Scale (VAS) score and total effective rate (P>0.05). Conclusion Compared to filiform needle therapy, fire-needle therapy can produce a better recovery rate and motor function of shoulder joint in treating scapulohumeral periarthritis.

Objective To investigate the cellular and molecular mechanisms of the anti-inflammatory effect of peroxisome proliferator-activated receptor α (PPARαt).Methods Firstly,bone marrow-derived macrophages (BMDMs) were randomly divided into control group,LPS group,WY14643 10 μmol/L group,WY14643 25 μmol/L group,and WY14643 50 μmol/L group using a random number table.Secondly,BMDMs were randomly dividcd into LPS group,WY14643+LPS group,and 3-MA+WY14643+LPS group.Primary BMDMs were stimulated by LPS (20 ng/ml) to establish the cellular model of inflammation.The selective agonist of PPARα WY14643 was administered at doses of 10,25,and 50 μmol/L (50 μmol/L for the second part of the experiment) at 2 hours before model establishment.The autophagy inhibitor 3-MA was administered at a dose of 10 mmol/L at 2 hours before model establishment.The cells in the control group were treated with dimethylsulfoxide (DMSO) at the same dose.The calls were transfected with GFP-LC3 plasmids at 24 hours before model establishment.The cells were harvested at 6 hours after LPS stimulation and related tests were performed.Green fluorescent protein was measured under a fluorescence microscope to evaluate autophagy activity.Quantitative real-time PCR was used to measure tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),interleukin-6 (IL-6),and mRNA expression of chemokine-1 (CXCL-1) and chemokine-10 (CXCL-10).Westem blot was used to measure PPARα and autophagy-related proteins LC3,ATG-5,ATG-7,and LAMP-1.A one-way analysis of variance was used for comparison between groups,and the LSD-t test was used for comparison between any two groups.Results In vitro,PPARα activation inhibited LPS-induced inflammatory response in primary macrophages in a dose-dependent manner.The results of gene expression showed that the relative expression of TNF-α,IL-1β,IL-6,CXCL-1,and CXCL-10 was as follows in the control group,LPS group,WY14643 10 μmol group,WY14643 25 μmol group,and WY14643 50 μmol group:TNF-α (0.085±0.009,4.065±0.544,3.281±0.368,1.780±±0.293,and 0.781±0.303,P ＜ 0.01),IL-1β (0.081±0.017,0.776±0.303,0.225±0.154,0.161±0.068,and 0.101±0.025,P ＜ 0.05),IL-6 (0.041±0.011,0.189±0.014,0.144±0.033,0.126±0.013,and 0.048±0.015,P ＜ 0.01),CXCL-1 (0.051±0.011,0.515±0.145,0.356±0.078,0.257±0.068,and 0.069±0.030,P ＜ 0.01),and CXCL-10 (0.126±0.068,0.831±0.093,0.508±0245,0.474±0.047,and 0.204±0.021,P ＜ 0.05).In vitro,PPARα activation promoted autophagy in vitro in a dose-dependent manner.The results of Westem blot and fluorescence microscopy in the control group,LPS group,WY14643 10 μmol group,WY14643 25 μmol group,and WY14643 50 μmol group showed that the expression of autophagy-related proteins and autophagosome formation gradually increased with the increasing concentration of WY14643.In vitro,WY 14643 inhibited autophagy,promoted inflammatory response in primary macrophages,and reversed the anti-inflammatory effect of PPARα.The results of gene expression showed that the relative expression of TNF-α,IL-1β,IL-6,CXCL-1,and CXCL-10 was as follows in the LPS group,WY14643+LPS group,and 3-MA+WY14643+LPS group:TNFα (4.327±.478,1.218±0.424,and 3.901±0.447,P ＜ 0.05),1L-1β (4.277±0.407,1.418±0.424,and 3.029±0.192,P ＜ 0.01),IL-6 (4.175±0.549,1.373±0.499,and 4.031±0.475,P ＜ 0.05),CXCL-1 (8.199±1.149,2.024±0.547,and 5.973±0.843,P ＜ 0.05),and CXCL-10 (1.208±0.148,0.206±0.069,and 0.798±0.170,P ＜ 0.05).Conclusion PPARα can promote cell autophagy and inhibit inflammatory response and may become a new therapeutic target for clinical prevention and treatment of inflammatory disease.

Objective To analyze the clinical,pathological and CT features of mediastinal carcinoid so as to improve the diagnostic accuracy.Methods The clinical,pathological and imaging data of 4 patients with mediastinal carcinoid were analyzed retrospectively.Results All 4 patients were elderly male,in which 3 cases had elevated serum neuron specific enolase(NSE)before operation and other one was not examined.All tumors were atypical carcinoid with Ki-67 expression of 5％-25％and positive expression of Syn,CD56,CK and CgA.The CT showed the lateral mass on the left(n=3)or both(n=1)sides of the anterior mediastinum,3 of which grew along the vascular space and could not be clearly demarcated from the pericardium and cardiovascular system.The lesions were large with irregular shape in 3 cases and round shape in 1 case,with heterogeneous density in 3 cases and homogeneous density in 1 case,with intratumoral calcification in 2 cases.Contrast enhanced CT showed the lesions with mild or moderate progressive enhancement,3 of which had supplying vessels from internal thoracic artery.The enlarged mediastinal lymph nodes were found in 3 cases and bone metastasis was in 1 case.Conclusion Mediastinal carcinoid is more common in elderly male,usually with elevated serum NSE.CT shows lateral mass in the anterior mediastinum with heterogeneous density,intratumoral calcification,mild or moderate progressive enhancement,and supplying vessels from internal thoracic artery.The larger lesion is indistinguishable from the adjacent lung tissue and cardiovascular system,usually with intrathoracic and extrathoracic lymph node metastasis.

Objective To determine the anti-lung cancer effect of koumine(KOU)and total alkaloids of Gelsemium elegans Benth(TAG)and investigate the underlying mechanism.Methods After low,medium and high concentrations(100,150,200 μg/mL)of KOU were used to treat human lung adenocarcinoma cell lines A549 and SPCA1,Live Cell Imaging and Analysis by Sartorius colony formation assay was employed to detect the cell proliferation.The transplanted tumor model of lung cancer cells in mice was constructed and divided into model group(model group),cyclophosphamide group(CTX group,20 mg/kg),KOU group(2 mg/kg)and TAG group(0.5 mg/kg).After the mice of the CTX,KOU and TAG groups were intraperitoneally injected with 0.1 mL/10 g corresponding agents every other day for 10 d,the growth of lung cancer solid tumors was observed grossly and with HE staining,immunohistochemical(IHC)assay and TUNEL staining to and calculate the tumor size and growth inhibitory rate.RNA sequencing analysis was performed on A549 cells treated with TAG for 48 h to screen the differentially expressed genes(DEGs)between the treatment group and the control group,and the obtained DEGs were further analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)functional enrichment analyses.RT-qPCR was applied to further analyze and verify the expression of related genes.Results Live Cell Imaging and Analysis fitted that the confluence of A549 and SPCA1 cells was decreased and the number of cells in the treated groups was observed to decrease,with poor growth.The results of colony formation assay confirmed that KOU reduced the number of cell clones,especially at a dose of 200 μg/mL(P＜0.01).Animal experiments showed that KOU and TAG treatment inhibited the tumor growth by 24.55％and 36.08％,respectively.TAG treatment resulted in significantly decreased tumor size when compared with the model group(P＜0.05).RNA sequencing analysis revealed that there were totally 2 793 DEGs,including 1 433 up-regulated genes and 1 360 down-regulated ones.Enrichment analysis displayed that the DEGs were mainly enriched in IL-17 signaling pathway,tumor necrosis factor signaling pathway and P53 signaling pathway.The results of RT-qPCR were consistent with the results of RNA sequencing analysis.The expression levels of GADD34,ZFP36,GADD45 A,GADD45 B and TP53INP2 genes were significantly increased in the TAG group(P＜0.01).Conclusion Alkaloids of Gelsemium elegans Benth inhibits the proliferation of lung cancer in vivo and in vitro.Transcriptomics find that KOU and TAG inhibit multiple DEGs and pathways of lung cancer.