Construction and validation of a nomogram model to predict the poor prognosis in patients with pulmonary cryptococcosis.

Background: Patients with poor prognosis of pulmonary cryptococcosis (PC) are prone to other complications such as meningeal infection, recurrence or even death. Therefore, this study aims to analyze the influencing factors in the poor prognosis of patients with PC, so as to build a predictive nomograph model of poor prognosis of PC, and verify the predictive performance of the model. Methods: This retrospective study included 410 patients (78.1%) with improved prognosis of PC and 115 patients (21.9%) with poor prognosis of PC. The 525 patients with PC were randomly divided into the training set and validation set according to the ratio of 7:3. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to screen the demographic information, including clinical characteristics, laboratory test indicators, comorbidity and treatment methods of patients, and other independent factors that affect the prognosis of PC. These factors were included in the multivariable logistic regression model to build a predictive nomograph. The receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to verify the accuracy and application value of the model. Results: It was finally confirmed that psychological symptoms, cytotoxic drugs, white blood cell count, hematocrit, platelet count, CRP, PCT, albumin, and CD4/CD8 were independent predictors of poor prognosis of PC patients. The area under the curve (AUC) of the predictive model for poor prognosis in the training set and validation set were 0.851 (95% CI: 0.818-0.881) and 0.949, respectively. At the same time, calibration curve and DCA results confirmed the excellent performance of the nomogram in predicting poor prognosis of PC. Conclusion: The nomograph model for predicting the poor prognosis of PC constructed in this study has good prediction ability, which is helpful for improving the prognosis of PC and further optimizing the clinical management strategy.

Discussion on the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation technology.

To explore the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation. The active ingredients and potential targets were screened by the Systematic Pharmacological Analysis Platform of Traditional Chinese Medicine (TCMSP). Hypertension-related targets were obtained from OMIM and GeneCards databases. Common targets between drug and hypertension were screened in the Venny platform. A protein-protein interaction (PPI) network was constructed in the STRING database using intersection targets. Key targets in PPI network were analyzed by Cytoscape. R language program was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding abilities of the main active ingredients to critical targets were verified by molecular simulation. Naringenin, quercetin, kaempferol, and ß-sitosterol in Lingguizhugan Decoction, and potential targets such as STAT3, AKT1, TNF, IL6, JUN, PTGS2, MMP9, CASP3, TP53, and MAPK3, were screened out. KEGG Enrichment analysis revealed that the common targets of Lingguizhugan Decoction and hypertension are mainly involved in the lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and IL17 signaling pathway. The molecular simulation results showed that naringenin-MAPK3, quercetin-MMP9, quercetin-PTGS2, and quercetin-TP53 were the top four in the docking scores. Naringenin-MAPK3 and quercetin-MMP9 were stable, with binding free energies of -27.97 ± 1.41 kcal/mol and -21.15 ± 3.17 kcal/mol, respectively. The possible mechanism of Lingguizhugan Decoction in treating hypertension is characterized of multi-component, multi-target, and multi-pathway.Communicated by Ramaswamy H. Sarma.

EIF4A3-induced circular RNA SCAP facilitates tumorigenesis and progression of non-small-cell lung cancer via miR-7/SMAD2 signaling.

The eukaryotic translation initiation factor 4A (eIF4A) family determines transcription efficiency by directly binding to precursor RNAs. One member, EIF4A3, modulates the expression of circRNAs. Circular RNA SCAP (circSCAP), a newly found circRNA, has been implicated in atherosclerosis. Yet, how circSCAP regulates cancer development and progression remains understudied. Here, we investigated the function of circSCAP and the molecular mechanism in the tumorigenesis and progression of non-small-cell lung cancer (NSCLC). CircSCAP was upregulated in both NSCLC tissues and cell lines and was mainly located in the cytoplasm. CircSCAP expression was promoted by EIF4A3, which was associated with poor prognosis in patients with NSCLC. CircSCAP sponged miR-7 to upregulate small mothers against decapentaplegic 2 (SMAD2). CircSCAP knockdown undermined cell proliferation, migration, and invasion abilities in NSCLC cell lines (SPCA1 and A549), which was rescued by either inhibiting miR-7 or overexpressing SMAD2. Moreover, circSCAP knockdown upregulated E-cadherin, while downregulating N-cadherin, Vimentin, and MMP9 in SPCA1 and A549 cells, which were abolished by either inhibiting miR-7 or overexpressing SMAD2. Additionally, miR-7 was markedly downregulated, whereas SMAD2 was significantly upregulated in NSCLC tissues. MiR-7 expression was inversely correlated with circSCAP and SMAD2 expression in NSCLC tissues. In conclusion, this study demonstrates that circSCAP is significantly upregulated in NSCLC cell lines and tissues and elucidates that circSCAP facilitates NSCLC progression by sponging miR-7 and upregulating SMAD2. The study provides a novel molecular target for early diagnosis and treatment of NSCLC.

Differential gene expression analysis and physiological response characteristics of passion fruit (Passiflora edulis) buds under high-temperature stress.

High temperature in summer is an unfavorable factor for passion fruit (Passiflora edulis), which can lead to restricted growth, short flowering period, few flower buds, low fruit setting rate, severe fruit drop, and more deformed fruit. To explore the molecular physiology mechanism of passion fruit responding to high-temperature stress, we use 'Zhuangxiang Mibao', a hybrid passion fruit cultivar, as the test material. Several physiological indicators were measured and compared between high-temperature (average temperature 38 °C) and normal temperature (average temperature 25 °C) conditions, including photosynthesis, chlorophyll fluorescence parameters, peroxidase activity (POD), superoxide dismutase activity (SOD) and malondialdehyde content. We performed RNA-seq analysis combined with biochemistry experiment to investigate the gene and molecular pathways that respond to high-temperature stress. The results showed that some physiological indicators in the high-temperature group, including the net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, transpiration rate, and the maximum chemical quantum yield of photosystemII (PSII), were significantly lower than those of the control group. Malondialdehyde content was substantially higher than the control group, while superoxide dismutase and superoxide dismutase activities decreased to different degrees. Transcriptome sequencing analysis showed that 140 genes were up-regulated and 75 genes were down-regulated under high-temperature stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis of differentially expressed genes revealed many metabolic pathways related to high-temperature stress. Further investigation revealed that 30 genes might be related to high-temperature stress, such as chlorophyllide a oxygenase (CAO), glutathione (GSH), WRKY transcription factors (WRKY), and heat shock protein (HSP), which have also been reported in other species. The results of real-time fluorescence quantitative PCR and RNA-seq of randomly selected ten genes are consistent, which suggests that the transcriptome sequencing results were reliable. Our study provides a theoretical basis for the mechanism of passion fruit response to high-temperature stress. Also, it gives a theoretical basis for the subsequent breeding of new heat-resistant passion fruit varieties.

Sex-specific meiosis responses to Gsdf in medaka (Oryzias latipes).

The meiotic entry of undifferentiated germ cells is sexually specific and strictly regulated by the testicular or ovarian environment. Germline stem cells with a set of abnormal sex chromosomes and associated autosomes undergo defective meiotic processes and are eventually eliminated by yet to be defined post-transcriptional modifications. Herein, we report the role of gsdf, a member of BMP/TGFß family uniquely found in teleost, in the regulation of meiotic entry in medaka (Oryzias latipes) via analyses of gametogenesis in gsdf-deficient XX and XY gonads in comparison with their wild-type siblings. Several differentially expressed genes, including the FKB506-binding protein 7 (fkbp7), were significantly upregulated in pubertal gsdf-deficient gonads. The increase in alternative pre-mRNA isoforms of meiotic synaptonemal complex gene sycp3 was visualized using Integrative Genomics Viewer and confirmed by real-time qPCR. Nevertheless, immunofluorescence analysis showed that Sycp3 protein products reduced significantly in gsdf-deficient XY oocytes. Transmission electron microscope observations showed that normal synchronous cysts were replaced by asynchronous cysts in gsdf-deficient testis. Breeding experiments showed that the sex ratio deviation of gsdf-/- XY gametes in a non-Mendelian manner might be due to the non-segregation of XY chromosomes. Taken together, our results suggest that gsdf plays a role in the proper execution of cytoplasmic and nuclear events through receptor Smad phosphorylation and Sycp3 dephosphorylation to coordinate medaka gametogenesis, including sex-specific mitotic divisions and meiotic recombination.

Epidemiology, diagnosis and treatment of early COVID-19 patients in Jiaxing City, Zhejiang Province, China, January to March 2020.

BACKGROUND: Imported Coronavirus disease 2019 (COVID-19) patients pose a huge challenge to the prevention and control of the epidemic in prefecture-level cities in China. However, the treatment strategies at that time were mainly empirical and far from perfect. Hence, this study aims to summarize the clinical characteristics, diagnosis and treatment of all COVID-19 patients in Jiaxing City in 2020. METHODS: The clinical data of 42 patients diagnosed with COVID-19 in Jiaxing City, Zhejiang Province from January 23, 2020 to March 4, 2020 were retrospectively analyzed. Epidemiological history and sociodemographic data were collected. Laboratory parameters, imaging and disease progression, treatment methods, efficacy and adverse reactions of COVID-19 cases were recorded. Then, the clinical characteristics as well as diagnosis and treatment were statistically analyzed. RESULTS: The median age of 42 patients was 47 years old, including 24 males (57.1%) and 18 females (42.9%). There were 21 first-generation cases, 29 cases (69%) of clustering onset related to first-generation cases, and 28 cases without any underlying diseases. Radiographic progression was reported in 17 patients (40.5%) (progression duration, 2-11 days; median progression duration, 3.8 days; average progression duration, 4.59-2.48 days). The main clinical symptoms include fever (78.6%) and cough (64.3%). A total of 37 patients (88.10%) received arbidol combined with lopinavir/ritonavir or darunavir/cobicistat. Of these, 22 patients (52.4%) took a combination with moxifloxacin tablets, and 20 patients (47.6%) took combined hormone therapy. Seventeen patients (40.48%) reported diarrhea, nausea, vomiting, rash, and other adverse drug reactions. A total of 38 patients improved (90.5%). The hospital stays of 36 patients ranged from 7 to 33 days, with a median of 19 days (19.00-7.33 days on average). The virus nucleic acid test result return time was 1 to 32 days, with a median of 15.5 days (14.41-8.61 days on average). CONCLUSIONS: Most of the imported COVID-19 patients in Jiaxing City were of the first generation, mainly cluster onset, and the epidemiological characteristics were relatively simple. Arbidol combined with lopinavir/ritonavir or darunavir/cobicistat was the main treatment strategy for the initial treatment of COVID-19.

A Clinical Study on Microwave Ablation in Combination with Chemotherapy in Treating Peripheral IIIB-IV Non-Small Cell Lung Cancer.

Background: This study investigated the efficacy and complications of microwave ablation in combination with chemotherapy in treating peripheral IIIB-IV non-small cell lung cancer (NSCLC). Materials and Methods: A total of 100 patients with peripheral IIIB-IV NSCLC were randomly divided into two groups: combination group (n = 52) and chemotherapy group (n = 48). Patients in the combination group were treated with microwave ablation, radiotherapy, and chemotherapy, whereas the patients in the chemotherapy group were treated with pemetrexed disodium or gemcitabine hydrochloride, cisplatin chemotherapy, and conventional radiotherapy. Results: The effectiveness and disease control rates were significantly higher in the combination group than in the chemotherapy group (p < 0.05). The second- and third-year survival rates were significantly higher in the combination group than in the chemotherapy group (p < 0.05). However, patients in the combination group had no serious complications, and there were no intraoperative and perioperative deaths. Conclusions: Microwave ablation is safe and effective. Combination chemotherapy is superior to chemotherapy in treating peripheral IIIB-IV NSCLC in terms of effectiveness rate, disease control rate, and extended patient survival time.

High expression of hypoxia inducible factor 1α related with acquired resistant to EGFR tyrosine kinase inhibitors in NSCLC.

The acquired resistance of the first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a main factor leading to poor prognosis of non-small cell lung cancer (NSCLC), so we researched whether the high expression of hypoxia-inducible factor-1α (HIF-1α) in EGFR-TKIs sensitive NSCLC tissue tends to induce the acquired resistance. We detected the HIF-1α in normal lung tissue, EGFR-TKIs sensitive NSCLC tissue, the first generation EGFR-TKIs acquired resistant NSCLC tissue and acquired EGFR T790M mutation NSCLC tissue with the method of immunohistochemistry. Then, we compared the expression of HIF-1α in these tissues, and evaluate the effect of HIF-1α expression to the occurrence of acquired resistance. The expression of HIF-1α was much higher in the EGFR-TKIs sensitive NSCLC tissue than that in normal lung tissue. HIF-1α level became higher after the occurrence acquired resistance. There was negative correlation between HIF-1α level before receiving treatment and the time of acquired resistance occurring as well as the acquired EGFR T790M mutation occurring. As the treatment going on, EGFR-TKIs sensitivity rate of low HIF-1α level group was much higher than that of high level group. The high expression of HIF-1α related with the acquired resistance of the first generation EGFR-TKIs, and HIF-1α can be a biomarker to predict the early occurrence of acquired resistance.

A Potential Role for the Gsdf-eEF1α Complex in Inhibiting Germ Cell Proliferation: A Protein-Interaction Analysis in Medaka (Oryzias latipes) From a Proteomics Perspective.

Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in the mature medaka testis. As for the interaction with transforming growth factor ß-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired yeast 2-hybrid assay. Coimmunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastructural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (transforming growth factor ß) and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA, which may be fundamentally conserved across the phyla during sexual differentiation.

Development and Validation of a Seven-Gene Signature for Predicting the Prognosis of Lung Adenocarcinoma.

BACKGROUND: Prognosis is a main factor affecting the survival of patients with lung adenocarcinoma (LUAD), yet no robust prognostic model of high effectiveness has been developed. This study is aimed at constructing a stable and practicable gene signature-based model via bioinformatics methods for predicting the prognosis of LUAD sufferers. METHODS: The mRNA expression data were accessed from the TCGA-LUAD dataset, and paired clinical information was collected from the GDC website. R package "edgeR" was employed to select the differentially expressed genes (DEGs), which were then used for the construction of a gene signature-based model via univariate COX, Lasso, and multivariate COX regression analyses. Kaplan-Meier and ROC survival analyses were conducted to comprehensively evaluate the performance of the model in predicting LUAD prognosis, and an independent dataset GSE26939 was accessed for further validation. RESULTS: Totally, 1,655 DEGs were obtained, and a 7-gene signature-based risk score was developed and formulated as risk_score = 0.000245∗NTSR1 + (7.13E - 05)∗RHOV + 0.000505∗KLK8 + (7.01E - 05)∗TNS4 + 0.000288∗C1QTNF6 + 0.00044∗IVL + 0.000161∗B4GALNT2. Kaplan-Meier survival curves revealed that the survival rate of patients in the high-risk group was lower in both the TCGA-LUAD dataset and GSE26939 relative to that of patients in the low-risk group. The relationship between the risk score and clinical characteristics was further investigated, finding that the model was effective in prognosis prediction in the patients with different age (age > 65, age < 65) and TNM stage (N0&N1, T1&T2, and tumor stage I/II). In sum, our study provides a robust predictive model for LUAD prognosis, which boosts the clinical research on LUAD and helps to explore the mechanism underlying the occurrence and progression of LUAD.

Comparative clinical study on microwave ablation combined with gemcitabine and cisplatin or combined with pemetrexed and cisplatin in treatment of advanced NSCLC.

OBJECTIVE: Solving the limitations of single chemotherapy in the treatment of non-small cell lung cancer (NSCLC). METHODS: About 100 patients with NSCLC treated in First Hospital of Jiaxing, Zhejiang from June 2016 to June 2018 were selected and randomly divided into MPC group and MGC group, with 50 cases in each group. The patients in MPC group were treated with microwave ablation (MWA) combined with PC while patients in MGC group were given MWA combined with gemcitabine plus cisplatin (GC). The therapeutic effects of the two groups as well as the complications and adverse reactions (ADRs) were observed and recorded. RESULTS: There was no significant difference in disease response rate (MPC group 33.3% vs MGC group 32.0%), disease control rate (MPC group 86.4% vs MGC group 78.0%) and overall survival (1-, 2- and 3-year survival, MPC group 65%, 59%, 32.7% vs MGC group 58%, 46%, 30%) between the two groups. In addition, the ADR myelosuppression was slighter in MPC group. There were 12 cases (23%) developed myelosuppression in the MPC group and 20 cases (42%) in MGC group, with a significant difference between the two groups (P < 0.05). The treatment was interrupted for 0 case (0%) in MPC group because of myelosuppression while 4 cases (8.3%) in MGC group. CONCLUSION: The two therapeutic regimens have similar efficacy in treatment of advanced NSCLC, but MPC causes slighter myelosuppression and can be the first-line therapy for advanced NSCLC.

Environmental Governance Cooperative Behavior among Enterprises with Reputation Effect Based on Complex Networks Evolutionary Game Model.

This paper first portrays the equilibrium payoff of enterprise's cooperation of environmental governance based on the Cournot model. Secondly, the evolutionary game model in complex networks is adopted to depict the evolution of environmental governance cooperative behavior among enterprises. Further, the evolutionary process of environmental governance cooperative behavior of enterprises is simulated considering the supervision behavior of government and the reputation evaluation behavior of environmental social organization. The results show that the cooperation level of enterprise group under self-organization condition will reach a low level; the supervision of government can enhance the cooperation level of enterprise group with high betrayal tempatation while it has limited effect on enterprise group with low betrayal tempatation. The reputation evaluation behavior of environmental social organization can realize reputation effect to improve the the cooperation level of enterprise group with high betrayal tempatation. The enhance of reputation sensitivity can optimize equilibrium distribution of reputation and it can strengthen the reputation effect on cooperation level. Based on the analysis above, the suggestions to effectively improve cooperation level are given.

Loss of Gsdf leads to a dysregulation of Igf2bp3-mediated oocyte development in medaka.

Gonadal soma-derived factor (Gsdf) is a unique TGF-ß factor essential for both ovarian and testicular development in Hd-rR medaka (Oryzias latipes). However, the downstream genes regulated by Gsdf signaling remain unknown. Using a high-throughput proteomic approach, we identified a significant increase in the expression of the RNA-binding protein Igf2bp3 in gsdf-deficient ovaries. We verified this difference in transcription and protein expression against normal gonads using real-time PCR quantification and Western blotting. The genomic structure of igf2bp3 and the syntenic flanking segments are highly conserved across fish and mammals. igf2bp3 expression was correlated with oocyte development, which is consistent with the expression of the igf2bp3 ortholog Vg1-RBP/Vera in Xenopus. In contrast to the normal ovary, cysts of H3K27me3- and Igf2bp3-positive germ cells were dramatically increased in the one-month-old gsdf-deficient ovary, indicating that the gsdf depletion led to a dysregulation of Igf2bp3-mediated oocyte development. Our results provide novel insights into the Gsdf-Igf2bp3 signaling mechanisms that underlie the fundamental process of gametogenesis; these mechanisms may be well conserved across phyla.

Protective effects of tanshinone IIA on myocardial ischemia reperfusion injury by reducing oxidative stress, HMGB1 expression, and inflammatory reaction.

CONTEXT: Although there were reports on the protective functions of tanshinone IIA (TSA) on rat myocardial ischemia, the exerting mechanism has not been completely clarified. OBJECTIVE: An attempt was made to further verify the protective effect of TSA on myocardial ischemia reperfusion injury and elucidate its underlying mechanism. MATERIALS AND METHODS: The rats were given TSA (10, 20, and 40 mg/kg bw per day) in intraperitoneal injection for 15 d. Rami anterior descending branch of coronary artery was ligated for 30 min and then re-perfused for 120 min to establish a reperfusion model. Effects of TSA on the infarct area, creatine kinase (CK), aspartate aminotransferase (AST), high mobility group box B1 protein (HMGB1), and inflammation and oxidation were investigated. RESULTS: Compared with those in the IR group, infarct size percentages of rats' myocardium in L-TSA, M-TSA, and H-TSA groups were reduced by 1.21, 4.26, and 12.50%, respectively, CK activities by 7.4, 11.2, and 12.5%, respectively, and AST activities also declined (p < 0.05). Furthermore, compared with those in the IR group, SOD and GSH-Px activities increased, and MDA, TNF-α, IL-6, and iNOS levels decreased in L-TSA, M-TSA, and H-TSA groups (p < 0.05). Meanwhile, compared with those in the IR group, HMGB1 expressions in L-TSA, M-TSA, and H-TSA groups were lowered by 21.9, 32.4, and 35.6%, respectively. DISCUSSION AND CONCLUSION: The protective function of TSA on myocardial ischemia reperfusion injury may be possibly exerted by inhibiting the increase of ROS caused by the reperfusion to attenuate the expression of HMGB1 and inhibit inflammation.

Automated system for kinetic analysis of particle size distributions for pharmaceutically relevant systems.

Detailing the kinetics of particle formation for pharmaceutically relevant solutions is challenging, especially when considering the combination of formulations, containers, and timescales of clinical importance. This paper describes a method for using commercial software Automate with a stream-selector valve capable of sampling container solutions from within an environmental chamber. The tool was built to monitor changes in particle size distributions via instrumental particle counters but can be adapted to other solution-based sensors. The tool and methodology were demonstrated to be highly effective for measuring dynamic changes in emulsion globule distributions as a function of storage and mixing conditions important for parenteral nutrition. Higher levels of agitation induced the fastest growth of large globules (≥5 µm) while the gentler conditions actually showed a decrease in the number of these large globules. The same methodology recorded calcium phosphate precipitation kinetics as a function of [Ca(2+)] and pH. This automated system is readily adaptable to a wide range of pharmaceutically relevant systems where the particle size is expected to vary with time. This instrumentation can dramatically reduce the time and resources needed to probe complex formulation issues while providing new insights for monitoring the kinetics as a function of key variables.

Effect of Pseudomonas aeruginosa on the expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the airway of bronchiectasis patients.

OBJECTIVE: To study the expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the airway of bronchiectasis (BE) patients, and evaluate the effect of pseudomonas aeruginosa (PAE) on the expression of TIMP-1 and MMP-9. METHODS: In this case-control study, subjects were divided into BE group and control group, and the BE group was further divided into PAE group and other bacteria group based on the culture results of bronchoalveolar lavage fluid (BALF). BALF was obtained by bronchoscopy, the expressions of MMP-9 and TIMP-1 were determined by ELISA, then the ratio of TIMP-1/MMP-9 was calculated. Furthermore, the tissue of bronchic endomembrane was obtained by transbronchial biopsy and the expressions of MMP-9 and TIMP-1 were determined using immunohistochemical method. RESULTS: The levels of MMP-9 in the BALF of PAE group and other bacteria group were significantly higher than that in control group (P=0.0000 both), and the expressions of MMP-9 in bronchic endomembrane of PAE group and other bacteria group were also significantly higher (P=0.0421 and 0.0003, respectively). The level of TIMP-1 in BALF of PAE group was significantly lower than that in other bacteria group (P=0.0324). The ratio of TIMP-1/MMP-9 in BALF of BE group was significantly lower than that in control group(P=0.0000), and this ratio of PAE group was significantly lower than those in both other bacteria group and control group (P=0.0026 and 0.0000, respectively). CONCLUSION: PAE infection in BE patients can suppress the expression of TIMP-1 and stimulate the expression of MMP-9, and thus make the disease even worse.