Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

Objective:To analyze the drug-resistant gene loci of Mycoplasma pneumoniae (MP) using metagenomic next-generation sequencing (mNGS). Methods:From November 2022 to October 2023, 697 clinical samples (including sputum, alveolar lavage fluid and blood) of 686 children with Mycoplasma pneumoniae positive detected by mNGS were retrospectively analyzed. Samples were divided into intensive care unit (ICU) group and non-ICU group, Chi-square test was used to compare groups, and Mann-Kendall trend test was used to analyze the change trend of the detection rate of drug resistance gene loci over time. Results:Of the 697 samples, 164 were from the ICU group and 533 were from the non-ICU group. The detection rate of Mycoplasma pneumoniae resistance gene was 44.3% (309/697), and all detected drug-resistant gene loci of MP were A2063G. The detection rate of Mycoplasma pneumoniae in ICU group was 50.0% (82/164), and the detection rates of Mycoplasma pneumoniae resistance gene loci in sputum, alveolus lavage fluid and blood samples were 75.0% (18/24) and 48.4% (62/128), respectively. The detection rate in sputum was higher than alveolus lavage fluid samples ( χ2=5.72, P=0.017). The detection rate of Mycoplasma pneumoniae in non-ICU group was 42.6% (227/533), the detection rate of Mycoplasma pneumoniae resistance gene loci in sputum and alveolar lavage fluid was 40.0% (16/40), 44.3% (201/454), and no detection rate in blood samples (0/12). There was no significant difference in the detection rate of alveolar lavage fluid and sputum ( χ2=0.27, P=0.602). From November 2022 to October 2023, the detection rate of submitted samples showed an increasing trend month by month (overall: Z=3.99, ICU inspection group: Z=2.93, non-ICU group: Z=3.01, all P<0.01). Among the bacteria commonly detected with Mycoplasma pneumoniae, Streptococcus pneumoniae accounted for the highest proportion, the detection rate was 15.5% (108/697), and Epstein-Barr virus accounted for the highest proportion of 17.6% (123/697). Conclusions:From November 2022 to October 2023, the detection rate of Mycoplasma pneumoniae drug resistance gene loci showed an increasing trend. The detection rate of drug resistance gene loci in sputum samples of ICU group was higher than alveolus lavage fluid. No new drug resistance site were detected.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

Humans ; Multiple Pulmonary Nodules ; Lung ; Lung Neoplasms/surgery* ; Solitary Pulmonary Nodule/surgery* ; Bronchoscopy

Objective:To explore the predictive value of HACOR score [heart rate (H), acidosis (A), consciousness (C), oxygenation (O), and respiratory rate (R)] on the clinical outcome of non-invasive positive pressure ventilation in patients with pulmonary encephalopathy due to chronic obstructive pulmonary disease (COPD).Methods:A prospective study was conducted. The patients with COPD combined with pulmonary encephalopathy who were admitted to Henan Provincial People's Hospital from January 1, 2017 to June 1, 2021 and initially received non-invasive positive pressure ventilation were enrolled. Besides non-invasive positive pressure ventilation, standard medical treatments were delivered to these patients according to guidelines. The need for endotracheal intubation was judged as failure of non-invasive ventilation treatment. Early failure was defined as the need for endotracheal intubation within 48 hours of treatment, and late failure was defined as the need for endotracheal intubation 48 hours and later. The HACOR score at different time points after non-invasive ventilation, the length of intensive care unit (ICU) stay, the total length of hospital stay, and the clinical outcome were recorded. The above indexes of patients with non-invasive ventilation were compared between successful and failed groups. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive effect of HACOR score on the failure of non-invasive positive pressure ventilation in the treatment of COPD with pulmonary encephalopathy.Results:A total of 630 patients were evaluated, and 51 patients were enrolled, including 42 males (82.35%) and 9 females (17.65%), with a median age of 70.0 (62.0, 78.0) years old. Among the 51 patients, 36 patients (70.59%) were successfully treated with non-invasive ventilation and discharged from the hospital eventually, and 15 patients (29.41%) failed and switched to invasive ventilation, of which 10 patients (19.61%) were defined early failure, 5 patients (9.80%) were late failure. The length of ICU and the total length of hospital stay of the non-invasive ventilation successful group were significantly longer than those of the non-invasive ventilation failure group [length of ICU stay (days): 13.0 (10.0, 16.0) vs. 5.0 (3.0, 8.0), total length of hospital stay (days): 23.0 (12.0, 28.0) vs. 12.0 (9.0, 15.0), both P < 0.01]. The HACOR score of patients at 1-2 hours in the non-invasive ventilation failure group was significantly higher than that in the successful group [10.47 (6.00, 16.00) vs. 6.00 (3.25, 8.00), P < 0.05]. However, there was no significant difference in HACOR score before non-invasive ventilation and at 3-6 hours between the two groups. The ROC curve showed that the area under the ROC curve (AUC) of 1-2 hour HACOR score after non-invasive ventilation for predicting non-invasive ventilation failure in COPD patients with pulmonary encephalopathy was 0.686, and the 95% confidence interval (95% CI) was 0.504-0.868. When the best cut-off value was 10.50, the sensitivity was 60.03%, the specificity was 86.10%, positive predictive value was 91.23%, and negative predictive value was 47.21%. Conclusions:Non-invasive positive pressure ventilation could prevent 70.59% of COPD patients with pulmonary encephalopathy from intubation. HACOR score was valuable to predict non-invasive positive pressure ventilation failure in pulmonary encephalopathy patients due to COPD.

BACKGROUND: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. METHODS: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO2 nanoparticles as a protective carrier (MnO2 @Pol/HA hydrogel) for delivering BMSCs. RESULTS: The resulting MnO2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF). CONCLUSION This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Metastatic pheochromocytoma and paraganglioma(MPPGL)is a rare neuroendocrine tumour in which genetic factors play an important role.In recent years,with the continuous progress of genetic testing technol-ogy,more and more susceptibility genes have been proved to be associated with MPPGL,making early identifica-tion of MPPGL possible.Recent studies have shown that genes associated with the development of MPPGL include SDHA,SDHB,SDHC,SDHD,SDHAF2,FH,MDH2,VHL,IDH1,PDH1/2,SLC25A11,GOT2,DLST,CSDE1,MAML3,H3F3A,MERTK,PCDHGC3,and KIF1B,with SDHA,SDHB,SDHC,SDHD,and SDHAF2 being the common pathogenic genes.Potential mutations affect the clinical manifestations of MPPGL,such as malignant potential and genetic prediction,which can help to better understand the clinical course and treat accordingly.Genetic testing for pheochromocytomas and paragangliomas allows for early detection of genetic syndromes and facilitates close follow-up of high-risk patients.This article provides a review of the progress of research on susceptibility genes identified in MPPGL in recent years,with a view to providing a certain theoretical basis for further related research.