Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Mutational landscape of homologous recombination-related genes in small-cell lung cancer.

BACKGROUND: Homologous recombination deficiency (HRD) is a well-known biomarker which could predict poly-ADP ribose polymerase 1 (PARP) inhibitor and platinum drug response. As an aggressive cancer, small-cell lung cancer (SCLC) is sensitive to platinum drugs, but relapse occurs rapidly. Herein, we aim to illustrate the genomic alteration patterns of homologous recombination repair (HRR)-related genes in a Chinese SCLC cohort and further analyze the relationship among HRR gene mutations and known biomarkers of immune checkpoint inhibitor (ICI) response, including tumor mutation burden (TMB) and programmed cell death-ligand 1 (PD-L1) expression. METHODS: Next-generation sequencing (NGS)-based target capture sequencing of 543 cancer-related genes was performed to analyze the genomic profiles of 133 Chinese SCLC patients, and TMB was calculated. PD-L1 expression was evaluated in 90 out of 133 patients using the SP142 PD-L1 immunohistochemistry assay. RESULTS: Among the 133 patients with SCLC, 47 (35.3%) had HRR gene mutations. ATM (8.3%) was the most frequently mutated HRR gene in the cohort, followed by NBN (4.5%). Pathogenic somatic and germline mutations of HRR genes were identified in 11 (23.4%) and 4 (8.5%) patients, respectively. HRR gene mutations cooccurred with KMT2D gene mutations. There were several differences in genomic alterations between patients with HRR gene mutations (HRR-Mut) and without HRR mutations (HRR-WT). The results revealed that TP53 and RB1 were commonly mutated genes in both groups. Mutations in the KMT2D gene and genes in the RTK-RAS pathway occurred more frequently in the HRR-Mut group. Furthermore, we found that mutations in HRR genes were associated with high TMB (Wilcoxon, p = 0.048), but there was no correlation of HRR gene mutation status with PD-L1 expression. CONCLUSIONS: We exhaustively describe the genomic alteration profile of Chinese SCLC patients and provide further evidence that HRR gene mutations are prevalent in SCLC patients.

The expression of ß-Defensin-2, IL-22, IL-22R1 and IL-10R2 in rat model of Klebsiella pneumonia and their correlation with histological grades.

Backgrounds and Aims:Klebsiella pneumoniae represents the most common opportunistic pathogen contributing to Klebsiella pneumonia in hospital-acquired infections. Klebsiella pneumonia has a rapidly progressive clinical course and multi-drug resistant (MDR). Identification of the effective biochemical markers is crucial for improving early diagnosis and treatment of Klebsiella pneumonia. The aims of our study are to 1) investigate the expression of ß-Defensin-2(rßD2), IL-22, IL-22R1 and IL-10R2 in Klebsiella pneumonia-infected rats and 2) their association with the histological grades of Klebsiella pneumonia.Methods and Materials: Fifty specific pathogen free (SPF) male SD rats were randomly divided into two groups: control group (treated with normal saline) and pneumonia group (treated with K. pneumoniae). All animals were sacrificed 1 h, 12 h, 1 d, 3 d, 5 d post infection. The severity and property of pneumonia was evaluated by histopathologic observation and pathogen identification. The mRNA expression of rßD2, IL-22, IL-22R1 and IL-10R2 was measured by RT-qPCR assay. The expression of rßD2 in rat lung tissue was determined by Western blot analysis, and the level of IL-22 in rat serum was determined by ELISA.Results: Histopathologic examination and bacterial counting of lung tissues confirmed the successful establishment of rat pneumonia model. The gene expression of rßD2, IL-22, IL-22R1 and IL-10R2 in pneumonia rats were significantly higher than those in healthy control mice (P < 0.05). The expression of rßD2 was correlated with histological grades of Klebsiella pneumonia and the level of IL-22. RT-qPCR results showed that the peak expression of IL-22R1 appeared earlier than IL-10R2 in rat pneumonia model.Conclusions: The expression of rßD2 and IL-22 was increased significantly at early stage in rat Klebsiella pneumonia model, suggesting that IL-22 and rßD2 might serve as potential biomarkers for the early diagnosis of Klebsiella pneumonia.

Association of the glucocorticoid receptor D641V variant with steroid-resistant asthma: a case-control study.

OBJECTIVES: Several mutations of the glucocorticoid receptor (GR) gene cause malfunction of the protein, resulting in steroid resistance. In diseases other than asthma, the GR variants I559N, D641V, and V729I have been linked to steroid resistance. The aim of this study was to evaluate the link of these GR variants in steroid-resistant (SR) asthma in the Chinese Han population. METHODS: GR polymorphisms were determined in 64 SR asthma patients, 217 steroid-sensitive (SS) asthma patients and 221 healthy control (CTR) individuals. The analysis of the GR variants was performed using PCR-sequence specific primers according to the European Molecular Biology Laboratory database (NC_000005.8). In addition, ligand binding and serum cortisol levels were determined. RESULTS: Compared with SS asthma patients and CTRs, a significant lower frequency of the GR D641V variant AA genotype (P=0.003, 0.014, respectively) and the A allele (P=0.001, 0.009, respectively) was found in SR asthma patients. Furthermore, the equilibrium dissociation constant (Kd) of GR ligand binding in SR asthma patients with the GR D641V variant AA genotype was significantly lower compared with the AT or the TT genotype carriers (P=0.006, 0.016, respectively). There was no significant difference between the I559N and V729I GR variants on comparing SR asthma patients with SS asthma patients or CTRs. CONCLUSION: This study suggests that the D641V variant of the GR is probably associated with SR asthma in the Chinese Han population.

Immune response to fused core protein of hepatitis C virus and truncated tetanus toxin peptides in mice.

Because no vaccine or effective therapy is available, thousands of people with HCV have died in recent years. Cytotoxic T lymphocytes (CTLs) play a critical role in the host cellular immune response against HCV. CTL epitopes in HCV core protein have been identified and used in vaccine development. T helper epitopes could promote cytokine secretion and antibody production to fight HCV. Tetanus toxin, an immunogen with many T helper epitopes, was once used in HBV therapeutic vaccine design. Here, eukaryotic and prokaryotic expression vectors were constructed to express truncated fragments of tetanus toxin and core genes of HCV. HLAA2.1 transgenic mice were inoculated with a recombinant plasmid vehicle with these two heterogenic gene fragments, and this augmented the titres of antibody against HCV. Antigen-specific lymphocyte proliferation, Th1 and Th2 cytokine levels and the number of lysed cells were markedly increased in the combined immunization group compared to controls. These findings provide new insights into a potential role for T helper epitopes from tetanus toxin combined with protein from the HCV core gene, which has numerous CTL epitopes. This design strategy may aid in the development of new vaccines against HCV.

[Expression of apoptosis related protein in transforming growth factors-beta signaling pathway and its effects on the cell apoptosis in the lung tissues after acute pulmonary embolism].

OBJECTIVE: To study the expression changes in apoptosis related protein in transforming growth factors-beta signaling pathway (ARTS) in the lung tissues in a rat acute pulmonary embolism (APE) model and its effects on cell apoptosis. METHODS: A rat APE model was reproduced. Samples of lung tissues were harvested at time points of 1, 8, 24 and 48 hours after APE. Healthy rats were used as control. The changes in mRNA level of ARTS were identified by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the changes in its protein level, and also Bcl-2, Bcl-xL, XIAP and H2Ax proteins, which were related with ARTS-mediated cell apoptosis, were determined by Western blotting. Immunohistochemical method was employed to study the distribution and expression changes in ARTS in the lung tissue before and after APE. Apoptotic cells in lung tissue sections were identified by the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method. RESULTS: At different time points, the mRNA levels and the protein levels of ARTS significantly increased in the lung tissues of rats with APE at 1 hour and 48 hours (P<0.05 or P<0.01). The immunohistochemical study showed that ARTS had low expression levels and could not be detected in the normal lung tissue, but it was up-regulated obviously at 48 hours after APE, mainly expressed in the bronchial epithelium and the lung alveolar epithelium. Apoptotic cells could be observed in the lung tissue by TUNEL after APE and at the same time when the lung tissue cells exhibited lower levels of the anti-apoptotic proteins Bcl-2, Bcl-xL, and XIAP, as compared with controls. Apoptosis level (as evaluated by H2Ax, apoptotic marker staining) in the lung tissue cells was obviously raised compared with controls (P<0.05 or P<0.01). CONCLUSION: The expression of ARTS is up-regulated after APE, and ARTS-mediated apoptosis plays an important role in the cell apoptosis of lung tissue.