TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma.

BACKGROUND: TAP1 is an immunomodulation-related protein that plays different roles in various malignancies. This study investigated the transcriptional expression profile of TAP1 in uveal melanoma (UVM), revealed its potential biological interaction network, and determined its prognostic value. METHODS: CIBERSORT and ESTIMATE bioinformatic methods were used on data sourced from The Cancer Genome Atlas database (TCGA) to determine the correlation between TAP1 expression, UVM prognosis, biological characteristics, and immune infiltration. Gene set enrichment analysis (GSEA) was used to discover the signaling pathways associated with TAP1, while STRING database and CytoHubba were used to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, respectively. An overall survival (OS) prognostic model was constructed to test the predictive efficacy of TAP1, and its effect on the in vitro proliferation activity and metastatic potential of UVM cell line C918 cells was verified by RNA interference. RESULTS: There was a clear association between TAP1 expression and UVM patient prognosis. Upregulated TAP1 was strongly associated with a shorter survival time, higher likelihood of metastasis, and higher mortality outcomes. According to GSEA analysis, various immunity-related signaling pathways such as primary immunodeficiency were enriched in the presence of elevated TAP1 expression. A PPI network and a ceRNA network were constructed to show the interactions among mRNAs, miRNAs, and lncRNAs. Furthermore, TAP1 expression showed a significant positive correlation with immunoscore, stromal score, CD8+ T cells, and dendritic cells, whereas the correlation with B cells and neutrophils was negative. The Cox regression model and calibration plots confirmed a strong agreement between the estimated OS and actual observed patient values. In vitro silencing of TAP1 expression in C918 cells significantly inhibited cell proliferation and metastasis. CONCLUSIONS: This study is the first to demonstrate that TAP1 expression is positively correlated with clinicopathological factors and poor prognosis in UVM. In vitro experiments also verified that TAP1 is associated with C918 cell proliferation, apoptosis, and metastasis. These results suggest that TAP1 may function as an oncogene, prognostic marker, and importantly, as a novel therapeutic target in patients with UVM.

Parvularcula maris sp. nov., an algicidal bacterium isolated from seawater.

A taxonomic study was carried out on strain BGMRC 0090T, which was isolated from seawater. The isolate was a Gram-negative, aerobic, flagellated, rod-shaped bacterium with algicidal activity. Optimal growth was observed at 30 °C, pH 6.0 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain BGMRC 0090T belonged to the genus Parvularcula, with highest sequence similarity to Parvularcula lutaonensis CC-MMS-1T (98.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain BGMRC 0090T and five strains of the genus Parvularcula with publicly available genomes were below 84.0, 69.2 and 21.4 %, respectively. The genome of strain BGMRC 0090T was 3.2 Mb with 64.8 mol% DNA G+C content and encoded 2905 predicted proteins, three rRNA, 42 tRNA and four ncRNA genes. Some algicidal biosynthesis-associated genes were detected in the genome. Strain BGMRC 0090T contained Q-10 as the major quinone. The predominant fatty acids were identified as summed feature 8 (C18 : 1ω7c/ω6c) and C16 : 0. Based on the polyphasic evidence presented in this paper, strain BGMRC 0090T is concluded to represent a novel species of the genus Parvularcula, for which the name Parvularcula maris sp. nov. is proposed. The type strain is BGMRC 0090T (= KCTC 92591T=MCCC 1K08100T).

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves' Ophthalmopathy.

Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

CT-guided transthoracic pulmonary artery catheterization: an experimental study in a porcine model.

OBJECTIVES: We investigated the safety and feasibility of CT-guided transthoracic pulmonary artery catheterization (TPAC) in a porcine model. METHODS: Procedures were conducted on ten mature Bama miniature pigs. After anesthesia, chest CT was performed in the left lateral decubitus position to determine the puncture route. Under the guidance of multiple CT scans, the introducer sheath was inserted from the right chest wall of the pig into the right pulmonary artery using the Seldinger technique. Then, a catheter connected with a transducer was inserted into the sheath to measure the pulmonary artery pressure. Finally, an active approximator was used to close the puncture site on the pulmonary artery. The pigs were followed up for 8 weeks to evaluate the operation-related complications and survival. RESULTS: Ten of 11 CT-guided TPAC procedures were successfully performed on ten pigs, rendering a technical success rate of 90.9%. One pig had hemoptysis while the needle was being inserted during the first operation, and a second procedure was successfully conducted 17 days later. Other complications, including pulmonary bleeding along the needle track (3 of 11; 27.3%), unclosed pulmonary artery puncture sites (3 of 10; 30%), pneumothorax (1 of 11; 9.1%), and hemopericardium (1 of 11; 9.1%), spontaneously resolved without complication-specific treatment. The mean pulmonary arterial pressure was 32 ± 17.6 mmHg. All animals survived the procedure and reached the end of the follow-up period. CONCLUSIONS: CT-guided TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. KEY POINTS: • TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. • This novel approach allows for faster access to the pulmonary artery, and it might be easier to operate the tip of the catheter to super-select the intent branch of the pulmonary artery. • TPAC can be an alternative pulmonary artery intervention pathway in patients with mechanical right-heart valves, great-vessel transposition, and other obstacles.

Clinical characteristics and postoperative outcomes of systemic artery-to-pulmonary vessel fistula in hemoptysis patients.

OBJECTIVES: To investigate the clinical characteristics and outcomes on the success of bronchial arterial embolization (BAE) in patients with and without systemic artery-to-pulmonary vessel fistula (SA-PF) and to evaluate the feasibility of CTA in the assessment of SA-PF. METHODS: We retrospectively enrolled 420 consecutive patients that underwent BAE for hemoptysis control in our hospital from September 2011 to May 2019. The clinical characteristics, preprocedural CTA findings, BAE procedural findings, and follow-up outcomes were collected. Patients were divided into two groups according to DSA findings: patients with SA-PF and those without. RESULTS: A total of 184 (43.7%) patients presented with SA-PF. Pneumonia was less likely to be the concomitant condition in patients with SA-PF (p < 0.001). The mean number of culprit arteries per patient was significantly higher in patients with SA-PF compared to that in patients without SA-PF (p = 0.017). The SA-PF patients saw a greater probability of recurrence (HR: 2.782, 95% CI: 1.617-4.784, p < 0.001). SA-pulmonary venous fistula (SA-PVF) favored lower hemoptysis recurrence rate (HR: 0.199, 95%CI: 0.052-0.765, p = 0.019). SA-pulmonary artery fistula (SA-PAF) can be detected by optimized CTA protocol with a detection rate of 65.3% (49/75). CONCLUSIONS: The presence of SA-PF is an independent risk factor predicting early recurrence of hemoptysis after BAE. SA-PVF seems to be a protective factor for longer hemoptysis control compared to SA-PAF. Optimized preprocedural CTA is a reliable examination to identify SA-PAF. KEY POINTS: • The appearance of SA-PF is associated with a greater probability of early recurrent hemoptysis after bronchial artery embolization. • The presence of SA-PVF seems to be a protective factor for longer hemoptysis control after BAE compared to SA-PAF. • Optimized CTA protocol seems to be a promising auxiliary examination to detect SA-PAF.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 RNA on Surfaces in Quarantine Rooms.

We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination in 2 rooms of a quarantine hotel after 2 presymptomatic persons who stayed there were laboratory-confirmed as having coronavirus disease. We detected SARS-CoV-2 RNA on 8 (36%) of 22 surfaces, as well as on the pillow cover, sheet, and duvet cover.

Multidetector computed tomography angiography prior to bronchial artery embolization helps detect culprit ectopic bronchial arteries and non-bronchial systemic arteries originating from subclavian and internal mammary arteries and improve hemoptysis-free early survival rate in patients with hemoptysis.

OBJECTIVES: To compare the average number of culprit arteries per patient, clinical success rate, and hemoptysis-free survival rate between hemoptysis patients with multidetector computed tomography (MDCT) angiography prior to bronchial artery embolization (BAE) and those without preprocedural MDCT angiography METHODS: This retrospective study was approved by the institutional review board with waiver of patient informed consent. From September 2012 to March 2017, 157 consecutive hemoptysis patients had been undergoing BAE. Among them, 106 patients received preprocedural MDCT angiography (MDCT group), while 51 patients did not receive preprocedural MDCT angiography (control group). The average number of culprit arteries per patient, clinical success rate, and hemoptysis-free survival rate were compared between the two groups. RESULTS: The average number of culprit ectopic bronchial arteries and that of non-bronchial systemic arteries originating from the subclavian and internal mammary arteries per patient in the MDCT group were both significantly higher than those in the control group (0.15 ± 0.51 vs 0.04 ± 0.20, p = 0.022, and 0.17 ± 0.56 vs 0.08 ± 0.39, p = 0.040, respectively). The clinical success rate of BAE with preprocedural MDCT angiography tended to be higher than that without MDCT angiography (97.2 vs 88.2%, p = 0.057). Importantly, patients in the MDCT group had a significantly higher hemoptysis-free early survival rate compared to those in the control group (96.1 vs 86.7%, p = 0.031). CONCLUSIONS: Preprocedural MDCT angiography helps detect culprit ectopic bronchial arteries and non-bronchial systemic arteries originating from subclavian and internal mammary arteries during BAE, and can improve the hemoptysis-free early survival rate, which could be recommended as a regular examination prior to BAE in patients with hemoptysis. KEY POINTS: • Preprocedural MDCT angiography helps detect culprit ectopic bronchial arteries and NBSAs originating from subclavian and internal mammary arteries during BAE. • Conducting MDCT angiography prior to BAE can improve hemoptysis-free early survival rate in hemoptysis patients.

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from Hefei (2014-2015): genetic characteristics of antimicrobial resistance.

BACKGROUND: Antimicrobial resistance (AMR) and genetic determinants of resistance of N. gonorrhoeae isolates from Hefei, China, were characterized adding a breadth of information to the molecular epidemiology of gonococcal resistance in China. METHODS: 126 N. gonorrhoeae isolates from a hospital clinic in Hefei, were collected between January, 2014, and November, 2015. The minimum inhibitory concentration (MIC) of N. gonorrhoeae isolates for seven antimicrobials were determined by the agar dilution method. Isolates were tested for mutations in penA and mtrR genes and 23S rRNA, and also genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). RESULTS: All N. gonorrhoeae isolates were resistant to ciprofloxacin; 81.7% (103/126) to tetracycline and 73.8% (93/126) to penicillin. 39.7% (50/126) of isolates were penicillinase producing N. gonorrhoeae (PPNG), 31.7% (40/126) were tetracycline resistant N. gonorrhoeae (TRNG) and 28.6% (36/126) were resistant to azithromycin. While not fully resistant to extended spectrum cephalosporins (ESCs), a total of 14 isolates (11.1%) displayed decreased susceptibility to ceftriaxone (MIC ≥ 0.125 mg/L, n = 10), cefixime (MIC ≥ 0. 25 mg/L, n = 1) or to both ESCs (n = 3). penA mosaic alleles XXXV were found in all isolates that harbored decreased susceptibility to cefixime, except for one. Four mutations were found in mtrR genes and mutations A2143G and C2599T were identified in 23S rRNA. No isolates were resistant to spectinomycin. Gonococcal isolates were distributed into diverse NG-MAST sequence types (STs); 86 separate STs were identified. CONCLUSIONS: N. gonorrhoeae isolates from Hefei during 2014-2015, displayed high levels of resistance to antimicrobials that had been recommended previously for treatment of gonorrhea, e.g., penicillin, tetracycline and ciprofloxacin. The prevalence of resistance to azithromycin was also high (28.6%). No isolates were found to be fully resistant to spectinomycin, ceftriaxone or cefixime; however, 11.1% isolates, overall, had decreased susceptibility to ESCs.

Synthesis, biological evaluation and molecular docking of 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives as potential Staphylococcus aureus Sortase A inhibitors.

A series of novel 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives were designed, synthesized and evaluated for their in vitro inhibitory activities against Staphylococcus aureus Sortase A with known Sortase A inhibitor pHMB as positive compound (IC50=130µM). Most compounds exhibited excellent inhibitory activity (IC50=19.8-184.2µM). Structure-activity relationship studies demonstrated that substitution at 7-position and 2-position of benzoxazole had great influence on the activities. Specifically, the substituent at 7-position is indispensable for inhibitory activity. The molecular docking studies revealed the i-butyl amide group went towards the ß6/ß7 loop-ß8 substructure of the protein and the benzoxazole core lied in a hydrophobic pocket composed of Ala118, Val166, Val168, Val169 and Ile182, shaping the whole molecule into a L-shape mode to be recognized by Sortase A.

Genetic and environmental effects on the bone development of the hand and wrist in Chinese young twins.

We assessed genetic and environmental effects on bone development of the hand and wrist, and on key anthropometric measures in Chinese young twins. In total, 139 monozygotic and 95 dizygotic twin pairs aged from 5 to 18 years were recruited. The twin correlations of total hand and wrist scores for monozygotic (MZ) and dizygotic (DZ) twins were 0.71 and 0.36, respectively. Bivariate model analysis showed moderate genetic correlations only for total skeletal maturity vs. weight and total skeletal maturity vs. waist circumference (r, 0.51 and 0.46, respectively). Our findings demonstrated that genetic factors played important roles in bone development of the hand and wrist in Chinese young twins, and that these genetic effects might be distinct from those influencing anthropometric measures.

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from symptomatic men attending the Nanjing sexually transmitted diseases clinic (2011-2012): genetic characteristics of isolates with reduced sensitivity to ceftriaxone.

BACKGROUND: Evolving gonococcal antimicrobial resistance (AMR) poses a serious threat to public health. The aim of this study was to: update antimicrobial susceptibility data of Neisseria gonorrhoeae recently isolated in Nanjing, China and identify specific deteminants of antimicrobial resistance and gentoypes of isolates with decreased sensitivity to ceftriaxone. METHODS: 334 N. gonorrhoeae isolates were collected consecutively from symptomatic men attending the Nanjing STD Clinic between April 2011 and December 2012. The minimum inhibitory concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone were determined by agar plate dilution for each isolate. Penicillinase-producing N. gonorrhoeae (PPNG) and tetracycline-resistant N. gonorrhoeae (TRNG) were examined and typed for ß-lactamase and tetM encoding plasmids respectively. Isolates that displayed elevated MICs to ceftriaxone (MIC ≥0.125 mg/L) were also tested for mutations in penA, mtrR, porB1b, ponA and pilQ genes and characterized by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). RESULTS: 98.8% (330/334) of N. gonorrhoeae isolates were resistant to ciprofloxacin; 97.9% (327/334) to tetracycline and 67.7% (226/334) to penicillin. All isolates were susceptible to ceftriaxone (MIC ≤0.25 mg/L) and spectinomycin (MIC ≤32 mg/L). Plasmid mediated resistance was exhibited by 175/334 (52%) of isolates: 120/334 (36%) of isolates were PPNG and 104/334 (31%) were TRNG. 90.0% (108/120) of PPNG isolates carried the Asia type ß-lactamase encoding plasmid and 96% (100/104) of TRNG isolates carried the Dutch type tetM containing plasmid. Elevated MICs for ceftriaxone were present in 15 (4.5%) isolates; multiple mutations were found in penA, mtrR, porB1b and ponA genes. The 15 isolates were distributed into diverse NG-MAST sequence types; four different non-mosaic penA alleles were identified, including one new type. CONCLUSIONS: N. gonorrhoeae isolates in Nanjing generally retained similar antimicrobial resistance patterns to isolates obtained five years ago. Fluctuations in resistance plasmid profiles imply that genetic exchange among gonococcal strains is ongoing and is frequent. Ceftriaxone and spectinomycin remain treatments of choice of gonorrhea in Nanjing, however, decreased susceptibility to ceftriaxone and rising MICs for spectinomycin of N. gonorrhoeae isolates underscore the importance of maintaining surveillance for AMR (both phenotypic and genotypic).

A novel MVK missense mutation in one Chinese family with disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate kinase, (MVK) a gene know to play an important role in regulation of calcium-induced keratinocyte differentiation and proliferation, has recently been suggested as the disease-causing gene for DSAP. Here we report a direct sequencing analysis of this gene in 3 DSAP families, 6 sporadic cases, and 100 unrelated healthy controls. We detected a heterozygous T to A transition at nucleotide 205 in exon 3 of MVK gene in one familial case. This mutation will result in an amino acid change at codon 69 (P.Ser69Thr), which is from a serine codon (TCA) to a threonine codon (ACA). No such mutation was detected in the unaffected family members or the 100 unrelated healthy controls. Our results demonstrated a novel missense mutation in MVK gene. This will be valuable for the diagnosis of DSAP as well as for genetic counseling and prenatal diagnosis of affected families.

[Tissue cultivation of Lonicera macranthoides 'Yuleil'].

OBJECTIVE: To establish the rapid tissue propagation system of Lonicera macranthoides 'Yuleil ', in order to provide theoretical basis for industrialized seed cultivation. METHODS: Young stem and leaves of Lonicera macranthoides 'Yuleil' were used as explants, with MS as basic media, and added with different concentrations of plant growth regulators such as NAA, 6-BA, TDZ and IBA in different stages of tissue culture, in order to conduct a systematic study on callus induction, proliferation and differentiation, and stem axillary bud induction, proliferation, rooting and seedlings. RESULTS: Best sterilization time of explant was:stem for 2 - 3 min, leaves for 1 - 2 min. The optimal medium for callus induction was MS + 2,4-D 1.0 mg/L + 6-BA 0.1 mg/L. The optimal medium for axillary bud induction, callus proliferation, callus differentiation, bud proliferation and rooting was MS + 6-BA 1.0 mg/L + NAA 0.5 mg/L, MS + TDZ (0.2 - 1.0) mg/L + NAA (0.02 - 0.05) mg/L, MS + 6-BA (0.5 - 1.0) mg/L + NAA (0.02 - 0.05) mg/L, MS + 6-BA 1.5 mg/L + NAA 0.5 mg/L and 1/2MS + IBA 1.0 mg/L + NAA 0.2 mg/L, respectively. Tube seedlings was refined in matrix include pearlite and humus (1: 1), with the survival rate of more than 75%. CONCLUSION: The disinfection method suitable for explants and the medium combination suitable for callus induction, proliferation, differentiation as well as bud proliferation and rooting are screened out to establish the rapid cultivation system for Lonicera macranthoides 'Yuleil'.

Integration of Radiomics and Immune-Related Genes Signatures for Predicting Axillary Lymph Node Metastasis in Breast Cancer.

BACKGROUND: To develop a radiogenomics nomogram for predicting axillary lymph node (ALN) metastasis in breast cancer and reveal underlying associations between radiomics features and biological pathways. MATERIALS AND METHODS: This study included 1062 breast cancer patients, 90 patients with both DCE-MRI and gene expression data. The optimal immune-related genes and radiomics features associated with ALN metastasis were firstly calculated, and corresponding feature signatures were constructed to further validate their performances in predicting ALN metastasis. The radiogenomics nomogram for predicting the risk of ALN metastasis was established by integrating radiomics signature, immune-related genes (IRG) signature, and critical clinicopathological factors. Gene modules associated with key radiomics features were identified by weighted gene co-expression network analysis (WGCNA) and submitted to functional enrichment analysis. Gene set variation analysis (GSVA) and correlation analysis were performed to investigate the associations between radiomics features and biological pathways. RESULTS: The radiogenomics nomogram showed promising predictive power for predicting ALN metastasis, with AUCs of 0.973 and 0.928 in the training and testing groups, respectively. WGCNA and functional enrichment analysis revealed that gene modules associated with key radiomics features were mainly enriched in breast cancer metastasis-related pathways, such as focal adhesion, ECM-receptor interaction, and cell adhesion molecules. GSVA also identified pathway activities associated with radiomics features such as glycogen synthesis, integration of energy metabolism. CONCLUSION: The radiogenomics nomogram can serve as an effective tool to predict the risk of ALN metastasis. This study provides further evidence that radiomics phenotypes may be driven by biological pathways related to breast cancer metastasis.

Rapid progress of an iris metastasis from esophageal cancer: a case report and review of literature.

This case report details a rare instance of rapid iris metastasis from esophageal cancer in a 59-year-old man. A literature review was conducted to explore recent advances in detecting, diagnosing, and treating intraocular metastatic malignancies. Positron emission tomography-computed tomography played a crucial role in identifying primary sites and systemic metastases. Local treatment combined with systemic therapy effectively reduced tumor size, preserved useful vision, and improved the patient's survival rate. A comparison was made of the characteristics of iris metastases from esophageal cancer and lung cancer, including age, gender, tumor characteristics, and treatment. The challenges associated with diagnosis and treatment are discussed, highlighting the implications for clinical practice.

Safety and efficacy of 12-week or longer indacaterol treatment in moderate-to-severe COPD patients: a systematic review.

BACKGROUND: This is a meta-analysis of the safety and efficacy of indacaterol in chronic obstructive pulmonary disease (COPD) with treatment duration of ≥12 weeks. METHODS: Randomized controlled trials (RCTs) reported in English (to September 30, 2012) were identified from PubMed, the Cochrane Library, Embase, websites, reference lists, and manual searches. Two reviewers independently assessed the quality of the trials and extracted information. RESULTS: Five RCTs were eligible. Five involved indacaterol, two salmeterol, one formoterol, and one tiotropium. Four studies had placebos. Using trough forced expiratory volume in 1 s as a measure of therapeutic effect, indacaterol was superior to the other ß2-agonists, tiotropium, and placebo at weeks 12, 26, and 52. Indacaterol had a greater effect on the transition dyspnoea index compared with placebo, formoterol, and salmeterol, but not open-label tiotropium. In reducing the as-needed use of salbutamol, indacaterol were superior to placebo, tiotropium, and formoterol, but not salmeterol (5, 95 % confidence interval (CI), -2.15, 12.15). Indacaterol improved St George's Respiratory Questionnaire scores more than placebo and open-label tiotropium, but not formoterol. Indacaterol seemed to cause more adverse events than placebo only at a dose of 600 µg daily and a duration of 52 weeks (risk ratio 1.15; 95 % CI, 1.04, 1.26). The total and serious adverse events and adverse events leading to discontinuation were comparable with open-label tiotropium and the ß2-agonists. CONCLUSIONS: Indacaterol is effective and well-tolerated as a bronchodilator for the maintenance of moderate to severe COPD.

Dynamic network biomarker to determine the critical point of breast cancer stage progression.

BACKGROUND: The discovery of early warning signs and biomarkers in patients with early breast cancer is crucial for the prevention and treatment of breast cancer. Dynamic Network Biomarker (DNB) is an approach based on nonlinear dynamics theory, which we exploited to identify a set of DNB members and their key genes as early warning signals during breast cancer staging progression. METHODS: First, based on the gene expression profile of breast cancer in the TCGA database, the DNB algorithm was used to calculate the composite index (CI) of each gene cluster in the process of breast cancer anatomical staging. Then we calculated gene modules associated with the clinical phenotype stage based on weighted gene co-expression network analysis (WGCNA), combined with DNB membership to identify key genes in the network. RESULTS: We identified a set of gene clusters with the highest CI in Stage II as DNBs, whose roles in related pathways indicate the emergence of a tipping point and impact on breast cancer development. In addition, analysis of the key gene GPRIN1 showed that high expression of GPRIN1 predicts poor prognosis, and related immune analysis showed that GPRIN1 is involved in the development of breast cancer through immune aspects. CONCLUSION: The discovery of DNBs and the key gene GPRIN1 can provide potential biomarkers and therapeutic targets for breast cancer.

Prognostic pyroptosis-related lncRNA signature predicts the efficacy of immunotherapy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a common malignant tumor of the liver, remains high incidence and poor prognosis. Although pyroptosis as well as lncRNA have been believed to play important roles in the tumorigenesis, diagnosis and prognosis, the role of pyroptosis-related lncRNAs (PRlncRs) in HCC remains obscure. Here, we identified 73 significantly differentially expressed and overall survival (OS) related pyroptosis-related lncRNAs (PRlncRs) in noncancerous and HCC samples. Based on LASSO regression and Cox regression analyses, we set up a novel prognostic model including six PRlncRs (MKLN1-AS, AC139491.2, AC145207.5, AC099850.3, AL590705.3 and AL049840.5), which showed good correlation with the OS of HCC patients. Considering that the risk score was negatively related to clinicopathologic features including T stage (T1-2 and T3-4), clinical stage (stage I-II and stage III-IV) and histological grade (G1, G2, G3 and G4), we further constructed a predictive nomogram containing the risk score and other clinicopathological features to predict the OS rates for HCC patients. In addition, the proposed signature was closely related to immune infiltration and offered improved clinical utility for immune checkpoint inhibitors (ICIs) strategies and chemotherapeutic drug selection in HCC. In conclusion, we established a considerable accurate risk signature consisting of 6 PRlncRs in HCC, which could predict the prognosis and efficacy of immunotherapy for HCC patients.

MiR-124-3p targeting PDE4B attenuates LPS-induced ALI through the TLR4/NF-κB signaling pathway.

BACKGROUND: A large number of studies have found that microRNAs (miRNAs) and phosphodiesterase 4 (PDE4) are crucial regulators of inflammatory responses in acute lung injury (ALI). OBJECTIVE: This study will explore the protective effect of miR-124-3p on ALI and its related mechanism. METHODS: The ALI mouse model was established by intratracheal administration of lipopolysaccharide (LPS) and evaluated by haematoxylin and eosin (HE) staining, lung injury score, inflammation factors, polymorphonuclear leukocyte (PMN) count, total protein and lung wet weight/dry weight (W/D) ratio. MiR-124-3p was overexpressed in vivo by intratracheal administration of miR-agomir, and PDE4B was expressed at low level in vivo by intratracheal administration of a PDE4B inhibitor. The mRNA expression level was detected by qRT-PCR, and the protein expression level was detected by Western blot. The relationship between miR-124-3p and PDE4B was detected by dual-luciferase activity assay. RESULTS: We found that miR-124-3p was downregulated in LPS-induced ALI. Overexpression of miR-124-3p alleviated lung injury by inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, we confirmed that miR-124-3p suppressed the TLR4/NF-κB signaling pathway by directly targeting PDE4B. CONCLUSION: miR-124-3p targeting PDE4B had a protective effect on LPS-induced ALI by inhibiting the TLR4/NF-κB signaling pathway.