Pulmonary granulomas and Mendelson syndrome in an immunocompromised patient.

Granuloma formation is generally correlated with infection. Pulmonary granulomas caused by foreign bodies aspiration are uncommon. The clinical and radiologic features of such cases often lack specificity, which makes it difficult to distinguish from malignancy. Aspiration is usually not considered in the differential diagnosis of patients presenting with mass-like abnormalities on chest imaging. Occult aspiration history, diverse clinical manifestations, atypical imaging findings, and limited availability of pathogen detection techniques make the precise diagnosis a substantial challenge. Herein, we describe an older patient presenting with chest pain and worrisome lung masses/nodules that proved to be pulmonary granulomas caused by foreign matters aspiration. In addition, the patient developed Mendelson syndrome due to acute macroaspiration. Lung tissue metagenomics next-generation sequencing (mNGS) revealed Streptococcus intermedius, a normal flora of the oropharynx. The aim of this case was to underscore the importance of considering aspiration as a potential differential diagnosis of patients presenting with pulmonary granulomas, especially in patients with recurrent pneumonia or predisposing factors. In addition, mNGS act as a potential, rapid, and effective technique for diagnosing aspiration-related syndrome, showing satisfactory performance in identifying pathogens.

Microbiological Profile of Patients with Aspiration Pneumonia Identified by Combined Detection Methods.

Purpose: Aspiration pneumonia (AP) challenges public health globally. The primary aim of this study was to ascertain the microbiological profile characteristics of patients with AP evaluated by combined detection methods, including conventional microbiological tests (CMTs), chips for complicated infection detection (CCID), and metagenomic next-generation sequencing (mNGS). Patients and Methods: From June 2021 to March 2022, a total of thirty-nine patients with AP or community-acquired pneumonia with aspiration risk factors (AspRF-CAP) from 3 hospitals were included. Respiratory specimens, including bronchoalveolar lavage fluid (BALF), sputum, and tracheal aspirate, were collected for microorganism detection. Results: Patients with AP were more inclined to be older, to have a shorter duration from illness onset to admission, to have a higher prevalence of different underlying diseases, particularly diabetes mellitus, chronic heart disease, and cerebrovascular disease, and to have a higher CURB-65 score (all P < 0.05). A total of 213 and 31 strains of microorganisms were detected in patients with AP and AspRF-CAP, respectively. The most common pathogens in AP were Corynebacterium striatum (17/213, 7.98%), Pseudomonas aeruginosa (15/213, 7.04%), Klebsiella pneumoniae (15/213, 7.04%), and Candida albicans (14/213, 6.57%). Besides, the most common pathogens in AspRF-CAP were Candida albicans (5/31, 16.13%), Pseudomonas aeruginosa (3/31, 9.68%) and Klebsiella pneumoniae (3/31, 9.68%). Moreover, Klebsiella pneumoniae (7/67, 10.45%) and Candida glabrata (5/67, 7.46%) were the most common pathogens among the 9 non-survived patients with AP. Conclusion: The prevalent pathogens detected in cases of AP were Corynebacterium striatum, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Early combined detection methods for patients with AP enhance the positive detection rate of pathogens and potentially expedites the initiation of appropriate antibiotic therapeutic strategies.

Clinical application of metagenomic next-generation sequencing for the diagnosis of suspected infection in adults: A cross-sectional study.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Identifying Risk Factors for Aspiration in Patients Hospitalized with Community-Acquired Pneumonia.

Background: Aspiration pneumonia (AP) is difficult to diagnose and has poor outcomes. This case-control study aimed to explore the risk factors and delineate the antibiotic usage for AP. Methods: Inpatients diagnosed with community-acquired pneumonia (CAP) from 2013 to 2017, enrolled in the urban employee basic medical insurance program in Beijing, were included and classified into the AP (N = 2,885) and non-AP (N = 53,825) groups. Risk factors were identified by logistic regression. Results: Older age (compared to 18-64 years, OR for 65-79 years: 4.3, 95% CI: 3.8-4.9; OR for >80 years: 6.3, 95% CI: 5.6-7.2), male (OR: 1.4, 95% CI: 1.3-1.5), cerebrovascular disease (OR: 3.1, 95% CI: 2.8-3.5), dementia (OR: 2.0, 95% CI: 1.8-2.1), vomiting (OR: 1.4, 95% CI: 1.2-1.7), Parkinson's disease (OR: 2.1, 95% CI: 1.8-2.4), and epilepsy (OR: 3.2, 95% CI: 2.8-3.7) were associated with an increased risk of AP. 92.8% of the AP patients received antibiotic therapy. Among them, patients treated with broad-spectrum antibiotics, antibiotics for injection, and combined antibiotics accounted for 93.3%, 97.9%, and 81.7%, respectively. Conclusions: Older age, male, and several comorbidities were independent risk factors for AP, and combined antibiotics treatments are common, which merits attention in accurate detection of AP in a high-risk population.

Clinical Value of Metagenomics Next-Generation Sequencing in Antibiotic Resistance of a Patient with Severe Refractory Mycoplasma pneumoniae Pneumonia: A Case Report.

Background: Mycoplasma pneumoniae is an important infectious pathogen of lower respiratory tract infection in children and adolescents. Macrolide resistant M. pneumoniae (MRMP) has become increasingly prevalent, and identifying pathogen resistance genes is crucial for treatment. Case Presentation: We report a patient with severe refractory M. pneumoniae pneumonia (MPP). The failure of initial clinical treatment prompted the re-analysis of metagenomic next-generation sequencing (mNGS) data for macrolide-resistant gene. Macrolide-resistance 23S ribosomal RNA gene was confirmed with read depth of 64 X for the A2063G mutation, which can decrease the affinity of macrolide with M. pneumoniae ribosome resulting in macrolide resistance. Furthermore, antimicrobial susceptibility testing demonstrated that M. pneumoniae was resistant to macrolide. PCR confirmatory test about M. pneumoniae resistance A2063G mutation, clinical treatment course and prognosis with altered treatment strategy, and M. pneumoniae antimicrobial susceptibility confirmed that the severe refractory MPP was due to macrolide resistant M. pneumoniae. Conclusion: As a new molecular level detection, mNGS is an effective method for detecting M. pneumoniae resistance genes. Early recognition of macrolide resistance and suitable antibiotics strategy is of vital importance for the prognosis of severe refractory MPP.

Predictive values of procalcitonin for coinfections in patients with COVID-19: a systematic review and meta-analysis.

OBJECTIVES: To assess the ability of procalcitonin (PCT)-a promising marker for coinfections-to predict coinfections in patients with COVID-19. METHODS: In this systematic review and meta-analysis, PubMed, Embase, Web of Science, Cochrane, the China National Knowledge Infrastructure (CNKI), and Wanfang were searched to identify eligible studies (up to August 30, 2021). Articles that reported the predictive value of PCT for coinfections in patients with COVID-19 were included. Individual and pooled sensitivities and specificities were reported, and I2 was used to test heterogeneity. This study was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42021283344). RESULTS: Five studies involving a total of 2775 patients reported the predictive value of PCT for coinfections in patients with COVID-19. The sensitivity, specificity, and area under the curve of PCT in predicting coinfections in the pooled studies were 0.60 (95% CI 0.35-0.81, I2 = 88.85), 0.71 (95% CI 0.58-0.81, I2 = 87.82), and 0.72(95% CI 0.68-0.76) respectively. CONCLUSIONS: Although PCT has limited predictive value for coinfections in patients with COVID-19, lower PCT levels seem to indicate a decreased probability of having a coinfection.

Diagnostic Value of Metagenomic Next-Generation Sequencing for Pneumonia in Immunocompromised Patients.

Introduction: The diagnosis of pulmonary infection and the identification of pathogens are still clinical challenges in immunocompromised patients. Metagenomic next-generation sequencing (mNGS) has emerged as a promising infection diagnostic technique. However, its diagnostic value in immunocompromised patients needs further exploration. Purposes: This study was to evaluate the diagnostic value of mNGS compared with comprehensive conventional pathogen tests (CTs) in the etiology of pneumonia in immunocompromised patients and immunocompetent patients. Methods: We retrospectively reviewed 53 patients who were diagnosed with pneumonia from May 2019 to June 2021. There were 32 immunocompromised patients and 21 immunocompetent patients with pneumonia who received both mNGS and CTs. The diagnostic performance was compared between mNGS and CTs in immunocompromised patients, using the composite diagnosis as the reference standard. And, the diagnostic value of mNGS for mixed infections was further analyzed. Results: Compared to immunocompetent patients, the most commonly pathogens, followed by Cytomegalovirus, Pneumocystis jirovecii and Klebsiella pneumoniae in immunocompromised patients. Furthermore, more mixed infections were diagnosed, and bacterial-fungal-virus coinfection was the most frequent combination (43.8%). mNGS can detect more types of pathogenic microorganisms than CTs in both groups (78.1% vs. 62.5%, P = 0.016and 57.1% vs. 42.9%, P = 0.048). The overall diagnostic positive rate of mNGS for pathogens was higher in immunocompromised patients (P = 0.002). In immunocompromised patients, a comparable diagnostic accuracy of mNGS and CTs was found for bacterial, fungal, and viral infections and coinfection. mNGS had a much higher sensitivity for bacterial infections (92.9% vs. 50%, P < 0.001) and coinfections (68.8% vs. 48.3%, P < 0.05), and it had no significant advantage in the detection of fungal infections, mainly due to the high sensitivity for Pneumocystis jirovecii in both groups. Conclusion: mNGS is more valuable in immunocompromised patients and exhibits apparent advantages in detecting bacterial and mixed infections. It may be an alternative or complementary diagnostic method for the diagnosis of complicated infections in immunocompromised patients.

Pneumocystis jirovecii and Mycobacterium tuberculosis Pulmonary Coinfection in an HIV-Seronegative Patient: A Case Report and Literature Review.

Background: Coinfection with Pneumocystis jirovecii and Mycobacterium tuberculosis is rare in HIV-seronegative patients. Because it is associated with unknown morbidity and a high mortality rate especially in patients with immunosuppression, health care practitioners should have a high index of suspicion when dealing with such patients. Case Presentation: A 66-year-old man with glucocorticoid therapy for 9 years had a fever after getting a cold and developed respiratory failure rapidly within 3 days. He was given trimethoprim-sulfamethoxazole empirically before Pneumocystis pneumonia (PCP) was confirmed with the presence of cysts in the sputum. Although there was a partial improvement of symptoms, an area of consolidation on the left upper lung lobe gradually enlarged. Bronchoscopy was performed 3 times and Mycobacterium tuberculosis infection was finally diagnosed. For 1 years, he was treated with standard antituberculosis agents, and his psychological well-being was managed using traditional Chinese medicine techniques. After 3 years of follow-up, his outcome was very good. Conclusion: HIV-seronegative patients on long-term glucocorticoid therapy in areas with a high incidence of Mycobacterium tuberculosis may be co-infected with Pneumocystis jirovecii. When opportunistic infections are suspected, diagnostic procedures including invasive ones should be performed as soon as possible and appropriate interventions need to be carried out promptly.

Rapid, accurate, and novel diagnostic technique for respiratory pathogens: Clinical application of loop-mediated isothermal amplification assay in older patients with pneumonia, a multicenter prospective observational study.

Background: Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method using only one type of enzyme that can amplify DNA with high specificity, efficiency and rapidity under isothermal conditions. Chips for Complicated Infection Detection (CCID) is based on LAMP. This study translate CCID into clinical application and evaluate its diagnostic value for pneumonia. Methods: Eighty one older patients with pneumonia were prospectively enrolled from January 1 to July 23, 2021, and 57 sputum/airway secretion and 35 bronchoalveolar lavage fluid samples were collected and analyzed by CCID and conventional microbiological tests (CMTs). Samples were collected, transported, monitored, and managed by a multidisciplinary team using a sample management information system. Results: CCID turnaround time was 50 min, and the detection limit was 500 copies/reaction. The percentage of positive samples was significantly higher using CCID than CMTs, especially for Klebsiella pneumoniae (odds ratio [OR], 9.0; 95% confidence interval [CI], 1.1-70.5; p < 0.05), Enterococcus faecalis (OR, ∞; p < 0.01), Stenotrophomonas maltophilia (OR, ∞; p < 0.01), fungi (OR, 26.0; 95% CI, 3.6-190.0; p < 0.01), and viruses (CCID only; p < 0.01). In addition, the percentage of positive results was significantly higher using CCID than CMTs in patients who used antibiotics for more than 3 days (91.9% vs. 64.9%; p < 0.01). Analyzing clinical impact, 55 cases (59.8%) benefited from CCID. Conclusion: CCID allows the rapid and accurate detection of pneumonia in older patients. Moreover, this technique is less affected by previous antibiotic treatment and can improve patient care.

Key determinants of misdiagnosis of tracheobronchial tuberculosis among senile patients in contemporary clinical practice: A retrospective analysis.

BACKGROUND: Tracheobronchial tuberculosis (TBTB) is a common subtype of pulmonary tuberculosis. Concomitant diseases often obscure the diagnosis of senile TBTB. AIM: To characterize senile patients with TBTB and to identify the potential causes of misdiagnosis. METHODS: One hundred twenty patients with senile TBTB who were admitted to the Anhui Chest hospital between May 2017 and May 2019 were retrospectively analyzed. Patients were classified as diagnosed group (n = 58) and misdiagnosed group (n = 62). Clinical manifestations, laboratory results, radiographic data, and endoscopic findings were compared between the two groups. RESULTS: Patients in the misdiagnosed group were most commonly diagnosed as pulmonary tuberculosis (non-TBTB, 29/62, 46.8%), general pneumonia (9/62, 14.5%), chronic obstructive pulmonary disease (8/62, 12.9%), and tracheobronchial carcinoma (7/62, 11.3%). The time elapsed between disease onset and confirmation of diagnosis was significantly longer in the misdiagnosed group [median (first quartile, third quartile): 6.32 (4.94, 16.02) mo vs 3.73 (2.37, 8.52) mo]. The misdiagnosed group had lower proportion of patients who underwent bronchoscopy [33.87% (21/62) vs 87.93% (51/58)], chest computed tomography (CT) scan [69.35% (43/62) vs 98.28% (57/58)], and those who showed CT signs of tuberculosis [27.91% (12/62) vs 50% (29/58)] as compared to that in the diagnosed group (P < 0.05). There were no significant between-group differences with respect to age, gender, occupation, clinical manifestations, or prevalence of comorbid chronic diseases (P > 0.05). CONCLUSION: Insufficient or inaccurate radiographic or bronchoscopic assessment was the predominant cause of delayed diagnosis of TBTB. Increased implementation and better interpretation of CT scan and early implementation of bronchoscopy can help reduce misdiagnosis of senile TBTB.

The Transcription Factor C/EBPß Promotes HFL-1 Cell Migration, Proliferation, and Inflammation by Activating lncRNA HAS2-AS1 in Hypoxia.

OBJECTIVE: Recent studies were widely concerned about the role of lncRNAs in hypoxic pulmonary hypertension (HPH). HAS2 was found significantly highly expressed in HPH, but the antisense of HAS2 (HAS2-AS1) has not been explored in HPH, providing a new potential therapeutic target of HPH. METHODS: In this study, human fetal lung fibroblast-1 (HFL-1) cells were cultured under hypoxia conditions to stimulate the pathological process of HPH. Transwell and wound-healing assays were used to detect HFL-1 cell migration, and CCK 8 assay was used to detect cell proliferation. The upstream transcription factor of HAS2-AS1 was predicted by JASPAR website, and the binding site between C/EBPß and HAS2-AS1 was predicted by JASPAR, too. In order to verify the association between C/EBPß and the HAS2 promoter region, we used chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene detection, western blot to detect the expression of inflammation-related proteins, and qRT-PCR to detect the expression of HAS2-AS1 and HAS2. Idiopathic pulmonary fibrosis (IPF) with HPH patient microarray data was downloaded from the GEO database and analyzed by R software. RESULTS: Our study showed that HAS2-AS1 and C/EBPß were highly expressed in hypoxic HFL-1 cells, and the knockdown of HAS2-AS1 expression could inhibit the proliferation, migration, and inflammatory response of HFL-1 cells. C/EBPß binds to the promoter region of HAS2-AS1 and has a positive regulation effect on the transcription of HAS2-AS1. Furthermore, C/EBPß can regulate the proliferation, migration, and inflammatory response of HFL-1 cells through HAS2-AS1. CONCLUSION: This study suggested that C/EBPß could upregulate HAS2-AS1 expression and induce HFL-1 cell proliferation, migration, and inflammation response.

Elevated Pulmonary Artery Systolic Pressure is Associated with Poor Survival of Patients with Non-Small Cell Lung Cancer.

PURPOSE: Pulmonary hypertension (PH) is an important comorbidity of lung cancer, PH in lung cancer patients is gradually gaining interest because of its apparent high prevalence, but the impact of PH on the outcomes of lung cancer remains uncertain and had rarely been discussed. We aimed to evaluate the prevalence, determinants and prognosis value of elevated pulmonary artery systolic pressure (PASP) in non-small cell lung cancer patients. PATIENTS AND METHODS: In this retrospective study, subjects with a new and pathological confirmed diagnosis of lung cancer were enrolled. All patients underwent transthoracic echocardiography before received treatment. Pulmonary artery systolic pressure was measured by transthoracic echocardiography. Lung cancer subtypes were categorized by WHO classification of lung tumors. Hazard ratios (HR) were estimated by using Cox regression models. RESULTS: Among 612 non-small cell lung cancer (NSCLC) patients, 19.8% coexisted with PH. After adjustment for age, symptom, coagulation disorders, lymph node metastasis, distant metastasis, histological type, clinical stage, PASP ≥35mmHg was significantly associated with the decreased overall survival (OS) of NSCLC (P= 0.028). Moreover, PASP ≥45mmHg was an independent predictor for perioperative death. Independent factors of comorbid elevated PASP were age, the presence of intrapulmonary metastasis and coagulation disorders. CONCLUSION: These findings suggest that PASP is an independent prognostic risk factor for NSCLC patients. Main determinants of elevated PASP are age, the presence of intrapulmonary metastasis and coagulation disorders.

Hsa_circ_0044226 knockdown attenuates progression of pulmonary fibrosis by inhibiting CDC27.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disorder. Here, we performed a bioinformatics analysis using the GSE102660 dataset from the Gene Expression Omnibus database to identify differentially expressed circRNAs (DEcircRNAs) in tissues from IPF patients and healthy controls. The results identified 45 DEcircRNAs, among which expression of hsa_circ_0044226 was markedly higher in lung tissues from IPF patients than from healthy controls. Knocking down hsa_circ_0044226 expression using a targeted shRNA inhibited TGF-ß1-induced fibrosis in RLE-6TN cells and in a bleomycin-induced mouse model of IPA. The diminished TGF-ß1-induced fibrosis was associated with upregulated expression of E-cadherin and downregulated expression of α-SMA, collagen III and fibronectin 1, as well as with reduced expression of CDC27, suggesting inhibition of epithelial-to-mesenchymal transition (EMT). All of those effects were reversed by overexpression of CDC27. This suggests CDC27 overexpression abolishes the antifibrotic effect of hsa_circ_0044226 knockdown through activation of EMT. Furthermore, hsa_circ_0044226 knockdown decreased the expression of CDC27 in BLM-induced pulmonary fibrosis mouse model. Collectively then, these findings indicate that downregulation of hsa_circ_0044226 attenuates pulmonary fibrosis in vitro and in vivo by inhibiting CDC27, which in turn suppresses EMT. This suggests hsa_circ_0044226 may be a useful therapeutic target for the treatment of IPF.

A rapid liquid biopsy of lung cancer by separation and detection of exfoliated tumor cells from bronchoalveolar lavage fluid with a dual-layer "PERFECT" filter system.

Separation and detection of exfoliated tumor cells (ETCs) from bronchoalveolar lavage fluid (BALF), namely the liquid biopsy of BALF, has been proved to be a valuable tool for the diagnosis of lung cancer. Herein, we established a rapid liquid biopsy of BALF based on a dual-layer PERFECT (precise, efficient, rapid, flexible, easy-to-operate, controllable and thin) filter system for the first time. Methods: The dual-layer PERFECT filter system consists of an upper-layer filter with large micropores (feature size of 49.4 ± 0.5 µm) and a lower-layer filter with small micropores (9.1 ± 0.1 µm). The upper-layer filter contributes to the isolation of cell clusters and removal of mucus from BALF samples, meanwhile the lower-layer one targets for the separation of single ETCs. First, separation of 10000 spiked A549s (cultured lung cancer cells) from 10 mL clinical BALF samples (n=3) were performed to investigate the performance of the proposed system in rare cell separation. Furthermore, separation and detection of ETCs and ETC clusters from clinical BALF samples were performed with this system to test its efficacy and compared with the routine cytocentrifuge. The clinical BALF samples were collected from 33 lung cancer-suspected patients with visible lesions under bronchoscope. The final histopathological results showed that 20 samples were from lung cancer positive patients while the other 13 cases were from lung cancer negative patients. Results: The recovery rate of spiked A549 cells from clinical BALF samples with the developed system (89.8 ± 5.2%) is significantly higher than that with the cytocentrifuge (13.6 ± 7.8%). In the preliminary clinical trial, although 33 clinical BALF samples with volume ranging from 6 mL to 18 mL showed greatly varied turbidity, filtrations could be finished within 3 min for 54.6% of samples (18/33), and 10 min at most for the rest. The dual-layer PERFECT filter system is proved to have a much higher sensitivity (80.0%, 95% CI: 55.7%-93.4%) than the routine cytocentrifuge (45.0%, 95% CI: 23.8%-68.0%), p=0.016 (McNemar test, two-tail). Moreover, the sensitivity of this platform is neither interfered by the variations of turbidity of the BALF samples, nor associated with the types of lung cancer. Conclusions: The easy and rapid processing of BALF samples with varying volume and turbidity, competitive sensitivity and good versatility for different lung cancer types will make the established dual-layer PERFECT filter system a promising approach for the liquid biopsy of BALF. The high-performance BALF-based liquid biopsy will improve the cytopathological identification and diagnosis of lung cancer.

Identification of PDL1-Related Biomarkers to Select Lung Adenocarcinoma Patients for PD1/PDL1 Inhibitors.

PD1/PDL1 inhibitors have been adopted for the treatment of advanced non-small-cell lung cancer, and PDL1 expression has been investigated as a predictive biomarker for PD1/PDL1 inhibitor therapy. However, PDL1 lacks diagnostic accuracy in differentiating patients who are likely or unlikely to benefit. So, it is urgent and clinically significant to identify other associated predictive biomarkers for PD1/PDL1 inhibitor therapy. Our work was to identify PDL1-related biomarkers that could improve the patient selection for PD1/PDL1 inhibitor treatment. We obtained 500 genes coexpressed with PDL1 in lung adenocarcinoma from the TCGA database. Then, we identified 125 out of 500 genes differentially expressed in lung adenocarcinoma. A total of 39 genes were distinguished with prognostic value and associated with overall survival. Median survival time analysis based on gene expression level, protein-protein interaction analysis, GO and KEGG enrichment analyses, and significant GO and KEGG function consistency analyses were conducted to screen candidate biomarkers. Three candidate genes, BRCA1, BRIP1, and EREG, were identified to be functionally significantly coexpressed with PDL1. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune response and cell activation. Additionally, to find potential adjuvant therapeutic targets in PD1/PDL1 inhibitor treatment, we performed transcription factor prediction analysis. A group of negative differential expression but PDL1-related biomarkers has been identified, which might help to assess the clinical management of lung cancer patients. A combination of potential biomarkers and adjuvant therapeutic targets with PDL1 will predict the response to PD1/PDL1 inhibitors more accurately and help with the patient selection for more personalized immune checkpoint inhibitor treatment.

Significance of alternative splicing in cancer cells.

OBJECTIVE: Alternative splicing can generate various structural and functional protein isoforms. Recently, accumulating evidence shows a relationship between alternative splicing and cancer. Cancer is a complex and chronic disease that involves malignant transformation. In this review, we consider alternative splicing events in relation to the hallmarks of cancer cells, and discuss current therapies to treat cancer-related to alternative splicing. DATA SOURCES: Data cited in this article are from the PubMed and Embase database, primarily focusing on research published from 2000 to 2018. STUDY SELECTION: Articles were selected with the search terms "alternative splicing," "cancer cell," "tumor microenvironment," and "therapy." RESULTS: Alternative splicing plays an important role in tumorigenesis, development, and escape from cell death. Taking this trait of cancer cells into consideration will allow more definite diagnoses of cancer, and allow the development of more effective medicines to intervene in cancer that could focus on controlling alternative splicing or competitively binding to the final products. CONCLUSIONS: Alternative splicing is common in cancer cells. Consideration of alternative splicing may allow different strategies for cancer therapy or the identification of novel biomarkers for cancer diagnosis.

Hypoxic mast cells accelerate the proliferation, collagen accumulation and phenotypic alteration of human lung fibroblasts.

Pulmonary vascular remodeling and fibrosis are the critical pathological characteristics of hypoxic pulmonary hypertension. Our previous study demonstrated that hypoxia is involved in the functional alteration of lung fibroblasts, but the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the effect of mast cells on the proliferation, function and phenotype of fibroblasts under hypoxic conditions. Hypoxia facilitated proliferation and the secretion of proinflammatory cytokines, including tumor necrosis factor (TNF)­α and interleukin (IL)­6, in human mast cells (HMC­1). RNA sequencing identified 2,077 upregulated and 2,418 downregulated mRNAs in human fetal lung fibroblasts (HFL­1) cultured in hypoxic conditioned medium from HMC­1 cells compared with normoxic controls, which are involved in various pathways, including extracellular matrix organization, cell proliferation and migration. Conditioned medium from hypoxic HMC­1 cells increased the proliferation and migration capacity of HFL­1 and triggered phenotypic transition from fibroblasts to myofibroblasts. A greater accumulation of collagen type I and III was also observed in an HFL­1 cell culture in hypoxic conditioned medium from HMC­1 cells, compared with HFL­1 cells cultured in normoxic control medium. The expression of matrix metalloproteinase (MMP)­9 and MMP­13 was upregulated in HFL­1 cells grown in hypoxic conditioned medium from HMC­1 cells. Similar pathological phenomena, including accumulation of mast cells, activated collagen metabolism and vascular remodeling, were observed in a hypoxic rat model. The results of the present study provide direct evidence that the multiple effects of the hypoxic microenvironment and mast cells on fibroblasts contribute to pulmonary vascular remodeling, and this process appears to be among the most important mechanisms underlying hypoxic pulmonary hypertension.

[Detection and Rectification of Radiation Emission from Medical Laser Equipment].

By introducing the unqualified cases of radiation emission test of medical laser equipment, this paper analyses the causes of the problems and the corrective measures adopted, and analyses the effectiveness of the corrective measures. It is proposed that the design rules and rules related to radiation emission should be mastered from the input stage of product design and development, and the radiation emission problem should be considered and solved as soon as possible.