Objective To study the relationships between airway inflammation,reticular basement membrane (RBM) thickness and bronchial hyperresponsiveness (BHR) before and after treatment with inhaled corticosteroids (ICS) in patients with asthma.Methods Twenty-eight patients with asthma (asthma group) were treated with inhaled budesonide (200 μg,twice a day for 12 months).Lung function,bronchoalveolar lavage (BAL) fluid and airway biopsy pathology were carried out before and after treatment.And 10 patients without asthma were acted as control group.Results BAL fluid eosinophils,epithelial cell and mast cell proportions before treatment in asthma group were significantly higher than those in control group [asthma group:(1.60 ±0.11)％,(2.50 ±0.29)％,(0.1100 ±0.0100)％ ;control group:(0.50 ±0.02)％,(1.20 ±0.08)％,(0.0200 ±0.0001)％,P ＜0.01].RBM and smooth muscle thickness were increased in asthma group than those in control group [ asthma group:( 14.25 ± 2.15 ),(0.36 ± 0.01 ) μ m;control group:(4.45 ± 1.22),(0.20 ± 0.01 ) μ m,P ＜ 0.01 ].BAL fluid eosinophils,epithelial cell and mast cell proportions,RBM and smooth muscle thickness decreased after treatment in asthma group [ (0.80 ±0.04)％,(1.60 ±0.07)％,(0.0500 ±0.0020)％,(6.18 ± 1.30) μm,(0.26 ±0.02) μm,P ＜0.01].RBM thickness was negative correlation with methacholine provoking dose which made forced expired volume in one second reduce by 20％ (r =-0.672,P ＜ 0.01 ).Conclusions Airway inflammation,RBM thickness and BHR in patients with asthma are interrelated and improved with ICS.The results of this study support the need for early and long treatment with ICS.

Objective To understand the status of Toxoplasma gondii infection in the population of Pu er City so as to pro-vide the evidence for formulating the strategy of toxoplasmosis control. Methods The population from Jingdong Jinggu and Menglian counties in Pu er City was surveyed IgG of T. gondii in serum was detected by ELISA. Results Totally 906 resident serum samples were detected and the IgG positive rate was 24.2%. The positive rates were higher in the aged groups of 30-39 years and 60-69 years and the difference among different aged groups was significant χ2=17.77 P 0.01 . There were no si-gnificant differences between different sexualities and among different educational levels and living habits P 0.05 . The posi-tive rates were 26.6% 194/730 15.5% 22/142 and 8.8% 3/34 in farmers students and other occupations respectively and there was a significant difference among them χ2=12.51 P 0.01 . The positive rates were 23.3% 198/849 and 36.8%21/57 in the farmers who had the habit of rearing pigs in pens and the farmers who had the habit of free ranging pigs respec-tively and there was a significant difference between them χ2=5.33 P 0.05 . Conclusion The IgG positive rate of T. go-ndii is very high in Pu er City and therefore the health education for toxoplasmosis control should be strengthened.

Objective To understand the status of soil?transmitted nematode infections in Xiding Township,Menghai Coun?ty,Yunnan Province,so as to provide the reference for formulating the strategy of soil?transmitted nematodosis control. Meth?ods Soil?transmitted nematode eggs in feces were detected by the Kato?Katz method,and the eggs of Enterobius vermicularis were detected by the cellophane tape method in children. The soil samples were collected from vegetable ,fruit and other crop fields of 15 residents randomly to detect hookworm. Results The stool samples from 1 002 residents were examined and the soil?transmitted nematode infection rate was 20.06%(201/1 002). The infection rates of hookworm,Ascaris lumbricoides and Trichu?ris trichura were 18.96%(190 cases),1.70%(17 cases)and 0.90%(9 cases)respectively. The percentages of people with light infection of hookworm,A. lumbricoides and T. trichura were 97.37%(185/190),88.24%(15/17)and 100%(9/9)respec?tively. No infection of E. vermicularis was found. Fifteen soil samples were tested,and no hookworm was found in the soil. Con?clusion The infection rate of soil?transmitted nematode in Xiding Township,Menghai County is high,but the infectiosity is light. The control and monitoring of soil?transmitted nematodosis should be strengthened in this area.

Objective:By analyzing the expression of pepsin in nasopharyngeal carcinoma (NPC) tissues, to investigate the correlation between laryngeal reflux (LPR) and NPC, as well as the effect of LPR on the quality of life of patients with NPC after radiotherapy.Methods:A total of 133 patients with NPC who underwent radiotherapy at the Department of Otorhinolaryngology of the Affiliated Hospital of Guizhou Medical University and the Affiliated Cancer Hospital of Guizhou Medical University from 2005 to 2019 were enrolled consecutively, including 90 males and 43 females, aged (44.32±7.47) years old. At the same period, 58 patients with chronic nasopharyngitis who underwent nasopharyngeal biopsy were selected as the control group. Immunohistochemical method was used to detect the expression of pepsin in nasopharyngeal specimens of the two groups. In addition, 188 normal individuals were selected as the normal group in the same period. NPC patients before and within 6 months after radiotherapy were inverstigated by the General Information Questionnaire and the Quality of Life Scale, and the pepsin levels in saliva of NPC patients before and after radiotherapy and the individuals in normal group were measured. SPSS 21.0 software was used for statistical analysis.Results:Pepsin expression in 133 specimens of NPC patients was strongly positive in 24 cases (18.05%), positive in 21 cases (15.79%), weakly positive in 69 cases (51.88%), and negative in 19 cases (14.29%). The specimens of control group had 10 cases of weakly positive (17.24%), 48 cases of negative (82.76%), but no strong positive or positive pepsin expression. The rate of positive pepsin expression in the NPC group was higher than that in the control group, with a statistically significant (χ 2=83.15, P<0.001). The pepsin content in the saliva of NPC patients after radiotherapy ((30.31±7.82) ng/ml) was higher than that before radiotherapy ((20.47±8.21) ng/ml) and the normal group (5.11±2.13) ng/ml), and the pepsin content in saliva before radiotherapy was higher than that in the normal group, and all differences were statistically significant (all P<0.05). After radiotherapy, the five functional domains of quality of life and overall quality of life of NPC patients decreased, while the related symptom scores increased (all P<0.05). Multiple linear regression analysis showed that pepsin content in saliva was the influential factor of five functional domains of quality of life, related symptoms and overall quality of life in NPC patients after radiotherapy (all P<0.05). Conclusion:The positive rate of pepsin expression in NPC tissues is high, and the pepsin in saliva before and after radiotherapy of NPC patients is significantly higher than that in normal, suggesting that LPR may be involved in the process of NPC and affect the quality of life after radiotherapy in NPC patients.

During the development of therapeutic microRNAs (miRNAs or miRs), it is essential to define their pharmacological actions. Rather, miRNA research and therapy mainly use miRNA mimics synthesized in vitro. After experimental screening of unique recombinant miRNAs produced in vivo, three lead antiproliferative miRNAs against human NSCLC cells, miR-22-3p, miR-9-5p, and miR-218-5p, were revealed to target folate metabolism by bioinformatic analyses. Recombinant miR-22-3p, miR-9-5p, and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells. Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs, inhibition of glucose uptake by miR-22-3p, and reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p in NSCLC cells. With greater activities to interrupt NSCLC cell respiration, glycolysis, and colony formation than miR-9-5p and -218-5p, recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity. These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine, which shall provide insight into developing antimetabolite RNA therapies.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors