Pseudomonas aeruginosa isolation is an important predictor for recurrent hemoptysis after bronchial artery embolization in patients with idiopathic bronchiectasis: a multicenter cohort study.

BACKGROUND: Nearly half of bronchiectasis patients receiving bronchial artery embolization (BAE) still have recurrent hemoptysis, which may be life-threatening. Worse still, the underlying risk factors of recurrence remain unknown. METHODS: A retrospective cohort was conducted of patients with idiopathic bronchiectasis who received BAE from 2015 to 2019 at eight centers. Patients were followed up for at least 24 months post BAE. Based on the outcomes of recurrent hemoptysis and recurrent severe hemoptysis, a Cox regression model was used to identify risk factors for recurrence. RESULTS: A total of 588 individuals were included. The median follow-up period was 34.0 months (interquartile range: 24.3-53.3 months). The 1-month, 1-year, 2-year, and 5-year cumulative recurrent hemoptysis-free rates were 87.2%, 67.5%, 57.6%, and 49.4%, respectively. The following factors were relative to recurrent hemoptysis: 24-h sputum volume (hazard ratio [HR] = 1.99 [95% confidence interval [95% CI]: 1.25-3.15, p = 0.015]), isolation of Pseudomonas aeruginosa (HR = 1.50 [95% CI: 1.13-2.00, p = 0.003]), extensive bronchiectasis (HR = 2.00 [95% CI: 1.29-3.09, p = 0.002]), and aberrant bronchial arteries (AbBAs) (HR = 1.45 [95% CI: 1.09-1.93, p = 0.014]). The area under the receiver operating characteristic curve of the nomogram was 0.728 [95% CI: 0.688-0.769]. CONCLUSIONS: Isolation of Pseudomonas aeruginosa is an important independent predictor of recurrent hemoptysis. The clearance of Pseudomonas aeruginosa might effectively reduce the hemoptysis recurrence rate.

An Experimental Pharmacokinetics Study of Diazepam and Its Metabolites in Oral Fluid of Chinese Population.

Diazepam abuse is widespread all over the word, leading to an increasing number of forensic cases such as suicide, drug-driving and robbery, but relevant studies are limited regarding the extraction of diazepam and its metabolites in oral fluid. This study aimed to investigate the pharmacokinetics of diazepam and its metabolites in oral fluid after a single oral dose in healthy volunteers. There was a total of 28 volunteers, and each ingested 5 mg diazepam orally, then ~2 mL oral fluid were collected from each participant at post-consumption time-points of prior (zero), 1, 2, 4, 8, 12, 24 h and 2, 3, 6, 12 and 15 days, respectively. All samples were extracted with solid-phase extraction and analyzed with high-performance liquid chromatography-tandem mass spectrometry method, and diazepam and nordazepam were detected in the oral fluid of volunteers. Pharmacokinetics of diazepam in oral fluid conformed to a two-compartment model, and k01_HL, k12_HL, k10_HL were 0.7 ± 1.1, 31.4 ± 68.5, 12.1 ± 11.6 h, respectively, nordazepam conformed to an one-compartment model, and k01_HL, k10_HL were 41.5 ± 44.8, 282.3 ± 365.5 h, respectively. Both diazepam and nordazepam could be detected continuously for 15 days, although there were individual differences, and the results regarding diazepam detecting in oral fluid will be of much help in forensic science and drug screening filed.

Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.

An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.

TMEM100 mediates inflammatory cytokines secretion in hepatic stellate cells and its mechanism research.

Recent studies have shown that Transmembrane protein 100 (TMEM100) is a gene at locus 17q32 encoding a 134-amino acid protein with two hypothetical transmembrane domainsa, and first identified as a transcript from the mouse genome. As a downstream target gene of bone morphogenetic protein (BMP)-activin receptor-like kinase 1 (ALK1) signaling, it was activated to participate in inducing arterial endothelium differentiation, maintaining vascular integrity, promoting cell apoptosis, inhibiting metastasis and proliferation of cancer cells. However, evidence for the function of TMEM100 in inflammation is still limited. In this study, we explore the role of TMEM100 in inflammatory cytokine secretion and the role of MAPK signaling pathways in tumor necrosis factor-alpha (TNF-α)-induced TMEM100 expression in LX-2 cells. We found that the expression of TMEM100 was decreased markedly in human liver fibrosis tissues, and its expression was also inhibited in LX-2 cells induced by TNF-α, suggesting that it might be associated with the development of inflammation. Therefore, we demonstrated that overexpression of TMEM100 by transfecting pEGFP-C2-TMEM100 could lead to the down-regulation of IL-1ß and IL-6 secretion. Moreover, we found that expression changes of TMEM100 could be involved in inhibition or activation of MAPK signaling pathways accompanied with regulating phosphorylation levels of ERK and JNK protein in response to TNF-α. These results suggested that TMEM100 might play an important role in the secretion of inflammatory cytokines (IL-1ß and IL-6) of LX-2 cells induced by TNF-α, and MAPK (ERK and JNK) signaling pathways might participate in its induction of expression.

microRNA-145-3p inhibits non-small cell lung cancer cell migration and invasion by targeting PDK1 via the mTOR signaling pathway.

The mammalian target of rapamycin (mTOR) pathway is dysregulated in more than 50% of all human malignancies and is a major target in cancer treatment. In this study, we explored the underlying mechanism involving microRNA-145-3p (miR-145-3p) in the development and progression of non-small cell lung cancer (NSCLC) by targeting PDK1 via the mTOR signaling pathway. NSCLC tissues and adjacent normal tissues were obtained from 83 NSCLC patients. miR-145-3p, PDK1, and mTOR levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Human NSCLC cell lines A549 and H1299 were transfected with miR-145-3p and siPDK1 to confirm the effect of miR-145-3p and PDK1 on NSCLC cells in vitro. Cell growth was evaluated by a CCK8 assay. Cell motility and chemotaxis analysis were determined by the scratch test and chemotaxis assay, respectively. The protein levels of PDK1 and mTOR were measured using the western blotting. Results showed lower level of miR-145-3p and higher levels of PDK1 and mTOR in NSCLC tissues compared to the adjacent normal tissues. In vitro results showed that cell growth, cell motility, and chemotaxis were all inhibited in cells transfected with miR-145-3p and those transfected with siPDK. Additionally, dual luciferase reporter gene assay helped confirmed that PDK1 is a target of miR-145. Finally, levels of PDK1, mTOR, and phosphorylated-mTOR were lower in cells transfected with miR-145-3p as well as those with siPDK1. These findings indicate that miR-145-3p may inhibit cell growth, motility, and chemotaxis in NSCLC by targeting PDK1 through suppressing the mTOR pathway.

Single Nucleotide Polymorphisms in the PTPN1 Gene Are Associated with Susceptibility to Esophageal Squamous Cell Carcinoma: A Case-Control Study in Inner Mongolia, China.

OBJECTIVE: This case-control study investigated the association of single nucleotide polymorphisms in the PTPN1 gene with susceptibility to esophageal squamous cell carcinoma (ESCC) in Inner Mongolia, China. METHODS: A total of 302 patients living in Inner Mongolia China who were pathologically diagnosed with ESCC between April 2012 and 2016 were selected for the ESCC group; 373 healthy individuals were selected for the control group. The rs2904268 C>G, rs2230605 A>G, and rs16995309 C>T polymorphisms in the PTPN1 gene were detected by bidirectional polymerase chain reaction amplification of specific alleles. The haplotype frequencies were analyzed by SHEsis software. Binary logistic regression analysis was conducted to analyze risk factors associated with ESCC. RESULTS: Statistical differences between the ESCC and control groups were observed for history of smoking, drinking, and poor eating habits (all p < 0.05). Both the rs2904268 C>G CG and GG genotype frequencies were markedly higher in the ESCC group relative to the control group (both p < 0.05). However, the genotype frequencies of rs2230605 A>G and rs16995309 C>T were similar between the ESCC and control groups (all p > 0.05). Compared with the control group, the ESCC group had notably elevated frequencies of the GGC and GAT haplotypes and significantly reduced frequencies of CGC and GGT haplotypes (all p < 0.05). A history of smoking, drinking, poor eating habits, the rs2904268 C>G CG+GG genotypes, and the GAT haplotype were all identified as risk factors for ESCC (all p < 0.05). CONCLUSION: These results indicated that the PTPN1 gene polymorphism rs2904268 is associated with susceptibility to ESCC in Inner Mongolia.

MicroRNA-218 inhibits the proliferation, migration, and invasion and promotes apoptosis of gastric cancer cells by targeting LASP1.

The present study aims to investigate the effects of microRNA-218 (miR-218) on the proliferation, migration, invasion, and apoptosis of gastric cancer (GC) cells by targeting LIM and SH3 domain protein 1 (LASP1). The GC cells in the logarithmic phase were selected and divided into five groups: the blank group, negative control (NC) group, miR-218 inhibitors group, miR-218 inhibitors + siLASP1 group, and miR-218 mimics + siLASP1 group. The miR-218 expression in each group was also detected by qRT-PCR. The CCK8 assay, Transwell migration, and invasion assays and flow cytometry were performed to determine the effects of miR-218 on cell proliferation, migration, invasion, and apoptosis of GC cells. Western blotting was conducted to measure LASP1 protein expression in GC cells after transfection. The qRT-PCR revealed that the transfection of miR-218 mimics could upregulate the miR-218 expression, and the transfection of miR-218 inhibitors could downregulate the miR-218 expression in the GC cells. Compared with the blank and NC groups, the proliferation, migration, and invasion of GC cells were significantly reduced in the miR-218 mimics, miR-218 inhibitors + siLASP1, and miR-218 mimics + siLASP1 groups but enhanced in the miR-218 inhibitors group. Similarly, compared with the blank and NC groups, the cell apoptosis rates in the miR-218 mimics, miR-218 inhibitors + siLASP1, and the miR-218 mimics + siLASP1 groups were significantly increased, while the miR-218 inhibitors group had a lower apoptosis rate. In conclusion, these results indicate that miR-218 could inhibit the proliferation, migration, and invasion and promote apoptosis of GC cells by downregulating LASP1 expression.

[PC-1 enhances c-myc gene expression in prostate cancer cells].

PC-1(Prostate and colon gene 1) gene belongs to TPD52 (Tumor Protein D52) gene family. The expression of PC-1 is found to promote androgen-independent progression. This study was conducted to assess the mechnism of promotion of androgen-independent progression in PC-1 gene. The c-myc gene expression was tested by RT-PCR and Western blotting analyses in the LNCaP-pc-1 and LNCaP-zero cell line. After separation of cytoplasm and nulear proteins of the LNCaP-pc-1 and LNCaP-zero cell line, the beta-catenin protein was detected by Western blotting. C4-2 cell line was used to examine the effects of 10058-F4 on the PC-1 gene expression. The results of RT-PCR and Western blotting indicated that PC-1 enhanced c-myc gene expression in prostate cancer cells, PC-1 was also found to enhance beta-catenin expression in nuclear. Furthermore, a small-molecule c-Myc inhibitor, 10058-F4 represses PC-1 gene expression in C4-2 cell line. Our findings suggest that PC-1 enhances c-myc gene expression in prostate cancer cells through the Wnt/beta-catenin pathway. Meanwhile, c-myc plays a feed-forward role in enhancing PC-1 driven c-myc gene expression, and promotes prostate an-drogen-independent progression.

The radiation response of androgen-refractory prostate cancer cell line C4-2 derived from androgen-sensitive cell line LNCaP.

Radiation therapy is a relatively effective therapeutic method for localized prostate cancer (PCa) patients. However, radioresistance occurs in nearly 30% of patients treated with potentially curative doses. Therapeutic synergy between radiotherapy and androgen ablation treatment provides a promising strategy for improving the clinical outcome. Accordingly, the androgen deprivation-induced signaling pathway may also mediate radiosensitivity in PCa cells. The C4-2 cell line was derived from the androgen-sensitive LNCaP parent line under androgen-depleted condition and had acquired androgen-refractory characteristics. In our study, the response to radiation was evaluated in both LNCaP and C4-2. Results showed that C4-2 cells were more likely to survive from irradiation and appeared more aggressive in their resistance to radiation treatment compared with LNCaP, as measured by clonogenic assays and cell viability and cell cycle analyses. Gene expression analyses revealed that a set of genes involved in cell cycle arrest and DNA repair were differentially regulated in LNCaP and C4-2 in response to radiation, which was also consistent with the radiation-resistant property observed in C4-2 cells. These results strongly suggested that the radiation-resistant property may develop with progression of PCa to androgen-independent status. Not only can the LNCaP and C4-2 PCa progression model be applied for investigating androgen-refractory progression, but it can also be used to explore the development of radiation resistance in PCa.