Understanding herpes zoster vaccine hesitancy and information asymmetry: a qualitative study in China.

Background: Herpes zoster is more prevalent among the older adult due to the age-related immune decline, leading to significant pain and complications. Although vaccination effectively prevents viral infections, vaccine hesitancy remains a major barrier to achieving high vaccination rates.To address this, we conducted a qualitative survey using Vaccine Hesitancy Determinants Matrix and 5C model to understand and improve vaccination rates in this group. Methods: Descriptive qualitative research design based on the philosophical underpinnings of naturalistic inquiry and purposive sampling methodology was conducted on adults aged 50 and above, as well as community health workers. Data were collected through semi-structured, in-depth personal interviews. The interview outline was constructed following a comprehensive review of the literature and consideration of the theoretical framework. Results: Seventeen adults over 50 years and four community healthcare workers were included in this study. The study found that information asymmetry in immunization planning was evident at all stages of vaccine supply, dissemination and demand. The main manifestations included limited access to authoritative information, insufficient community awareness of herpes zoster as a route of vaccination, insufficient vocational training, significant gaps in vaccine knowledge, and high levels of complacency among individual residents. Conclusion: Herpes zoster vaccine hesitancy is prevalent among middle-aged and older adults in China due to information asymmetry, vaccine complacency, inadequate community services, and other multiple layers of factors. Public health strategies should aim to reduce cognitive biases and information gaps by disseminating diverse and credible vaccine information through social media, medical institutions, and offline channels to promote higher vaccination rates.

Metabolic reprogramming-related gene classifier distinguishes malignant from the benign pulmonary nodules.

The current existing classifiers for distinguishing malignant from benign pulmonary nodules is limited by effectiveness or clinical practicality. In our study, we aimed to develop and validate a gene classifier for lung cancer diagnosis. To identify the genes involved in this process, we used the weighted gene co-expression network analysis to analyze gene expression datasets from Gene Expression Omnibus (GEO). We identified the three most relevant modules associated with malignant nodules and performed functional enrichment analysis on them. The results indicated significant involvement in metabolic, immune-related, cell cycle, and viral-related processes. All three modules showed enrichment in metabolic reprogramming pathways. Based on these genes, we intersected genes from the three modules with metabolic reprogramming-related genes and further intersected with differentially expressed genes to get 78 genes. After machine learning algorithms and manual selection, we finally got a nine-gene classifier consisting of SEC24D, RPSA, PSME3, PSMD8, PSMB7, NCOA1, MED12, LPCAT1, and AKR1C3. Our developed and validated classifier-based model demonstrated good discrimination, with an area under the curve (AUC) of 0.763 in the development cohort, 0.744 in the internal validation cohort, and 0.718 in the external validation cohort, and outperformed previous clinical models. Moreover, the addition of nodule size improved the predictive capability of the classifier. We further verify the expression of the gene in the classifier using TCGA lung cancer samples and found eight of the genes showed significant differential expression in lung adenocarcinoma while all nine genes showed significant differential expression in lung squamous carcinoma. Our findings underscore the significance of metabolic reprogramming pathways in patients with malignant pulmonary nodules, and our gene classifier can assist clinicians in differentiating benign from malignant pulmonary nodules in clinical settings.

Unraveling Herpes Zoster Vaccine Hesitancy, Acceptance, and Its Predictors: Insights From a Scoping Review.

Objectives: Herpes zoster vaccination is critical in preventing herpes zoster virus infection and its associated consequences. Despite its relevance, global herpes zoster immunisation coverage remains alarmingly low. Understanding the factors that drive vaccine scepticism and acceptance is crucial for increasing immunisation rates and improving public health outcomes. Methods: This scoping review, following Joanna Briggs Institute guidelines, included 18 studies examining vaccine hesitancy, acceptance, and associated factors. Meticulous data analysis revealed hesitancy's intricate dynamics across countries and demographics. Results: Studies displayed a wide range of acceptance rates (2.8%-89.02%), showcasing the complex interplay of attitudes and behaviors towards vaccination. Reasons for vaccine refusal were repeatedly identified in this setting, including worries about potential adverse effects, views of vaccine necessity, and vaccine supply constraints. Notably, individuals' patterns of vaccine acceptance and hesitancy differed among countries, vaccines, and vaccination-related factors. Conclusion: Addressing acceptance hurdles by improving accessibility, providing accurate information, and strengthening healthcare recommendations is crucial. Understanding the multifaceted factors influencing hesitancy allows for targeted interventions, elevating immunization rates and enhancing public health globally.

Characteristics and risk factors for advanced lung cancer with pulmonary embolism: A cross-sectional, case-control study.

OBJECTIVES: Pulmonary embolism (PE) is a life-threatening complication that can occur in patients with lung cancer. In this study, we aimed to identify risk factors and examine the clinical characteristics of advanced lung cancer patients with PE. METHODS: We conducted a retrospective review of patients admitted to our two hospitals between January 2020 and June 2022. The case group consisted of patients with lung cancer and PE, and a closely matched control group was included to identify risk factors. Statistical analysis was conducted using R language. RESULTS: A total of 4957 patients were reviewed, and 162 patients (comprising 54 cases and 108 controls) were included in this study. The prevalence of lung cancer with PE in the study population was 1.08%. The majority of patients were male, and the most common histological subtype was adenocarcinoma (67%), followed by squamous cell carcinoma, small cell carcinoma, and poorly differentiated non-small cell lung cancer. The majority of patients had a high performance status (PS) score, with 50% experiencing respiratory failure (mainly hypoxia) and 33% with deep vein thrombosis (DVT). Forty-eight percent of patients were diagnosed with concurrent PE. Further analysis showed that PE was an independent predictor of poor survival, and a PS score of >1 was an independent risk factor for PE in patients with lung cancer. CONCLUSION: Our study provides valuable insights into the epidemiology and prognosis of PE in lung cancer patients and suggests that a poor ECOG PS, which has not been previously reported, is an independent risk factor for PE.

POLRMT over-expression is linked to WNT/beta-catenin signaling, immune infiltration, and unfavorable outcomes in lung adenocarcinoma patients.

BACKGROUND: Mitochondrial RNA polymerase (POLRMT) is essential for the expression of mitochondrial genes. In recent studies, POLRMT expression promoted non-small cell cancer cell proliferation in cell lines and xenografts. The present study investigated the impact of POLRMT expression and function on lung adenocarcinoma (LUAD) patients. METHOD: Multi-omics data (genomics, transcriptomics, and proteomics) from publicly available databases were used to assess the role of POLRMT expression and function in LUAD. These findings were further verified using cancer tissues from clinical samples. RESULTS: POLRMT was over-expressed in LUADs, with mutation frequencies ranging from 1.30% to 5.71%. Over-expression of POLRMT was associated with an abnormal clinicopathological condition resulting in a decreased lifespan. Furthermore, gene sets enrich analysis revealed that POLRMT expression was linked to WNT/beta-catenin signaling; the expression of downstream target genes was positively correlated with POLRMT expression. Also, POLRMT expression was positively correlated with immunosuppressive genes, thereby affecting immune infiltration. CONCLUSION: POLRMT is over-expressed in LUAD, thereby impacting patient survival. It is also involved in WNT/beta-catenin signaling and may affect tumor infiltration.

Quantitative analysis of fucosylated glycoproteins by immobilized lectin-affinity fluorescent labeling.

Human biofluids are often used to discover disease-specific glycosylation, since abnormal changes in protein glycosylation can discern physiopathological states. Highly glycosylated proteins in biofluids make it possible to identify disease signatures. Glycoproteomic studies on saliva glycoproteins showed that fucosylation was significantly increased during tumorigenesis and that glycoproteins became hyperfucosylated in lung metastases, and tumor stage is associated with fucosylation. Quantification of salivary fucosylation can be achieved by mass spectrometric analysis of fucosylated glycoproteins or fucosylated glycans; however, the use of mass spectrometry is non-trivial for clinical practice. Here, we developed a high-throughput quantitative method, lectin-affinity fluorescent labeling quantification (LAFLQ), to quantify fucosylated glycoproteins without relying on mass spectrometry. Lectins with a specific affinity for fucoses are immobilized on the resin and effectively capture fluorescently labeled fucosylated glycoproteins, which are further quantitatively characterized by fluorescence detection in a 96-well plate. Our results demonstrated that serum IgG can be accurately quantified by lectin and fluorescence detection. Quantification in saliva showed significantly higher fucosylation in lung cancer patients compared to healthy controls or other non-cancer diseases, suggesting that this method has the potential to quantify stage-related fucosylation in lung cancer saliva.

Nomogram for predicting 90-day mortality in patients with Acinetobacter baumannii-caused hospital-acquired and ventilator-associated pneumonia in the respiratory intensive care unit.

OBJECTIVE: We built a prediction model of mortality risk in patients the with Acinetobacter baumannii (AB)-caused hospital-acquired (HAP) and ventilator-associated pneumonia (VAP). METHODS: In this retrospective study, 164 patients with AB lower respiratory tract infection were admitted to the respiratory intensive care unit (RICU) from January 2019 to August 2021 (29 with HAP, 135 with VAP) and grouped randomly into a training cohort (n = 115) and a validation cohort (n = 49). Least absolute shrinkage and selection operator regression and multivariate Cox regression were used to identify risk factors of 90-day mortality. We built a nomogram prediction model and evaluated model discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curves, respectively. RESULTS: Four predictors (days in intensive care unit, infection with carbapenem-resistant AB, days of carbapenem use within 90 days of isolating AB, and septic shock) were used to build the nomogram. The AUC of the two groups was 0.922 and 0.823, respectively. The predictive model was well-calibrated; decision curve analysis showed the proposed nomogram would obtain a net benefit with threshold probability between 1% and 100%. CONCLUSIONS: The nomogram model showed good performance, making it useful in managing patients with AB-caused HAP and VAP.

Facilitative role of circPVT1 in osteogenic differentiation potentials of bone marrow mesenchymal stem cells from patients with osteoporosis through the miR-30d-5p/ITGB3 axis.

OBJECTIVE: The critical role of circular RNAs (circRNAs) in osteoporosis (OP) has been highlighted. We tried to explore the role of circPVT1 in OP in relation to microRNA-30d-5p (miR-30d-5p) and ITGB3. METHODS: After bone marrow collection, bone marrow mesenchymal stem cells (BMSCs) were isolated and identified. Then, Pearson coefficient was used to analyze the correlation among circPVT1, miR-30d-5p and ITGB3, and the binding sites were predicted and verified. Gain- and loss-of function assays in circPVT1, miR-30d-5p and ITGB3 were performed to analyze their effect on osteogenic differentiation of BMSCs. RESULTS: The osteogenic differentiation of BMSCs from OP patients was significantly decreased, and reduced circPVT1 expression was found in the BMSCs from OP patients. Overexpression of circPVT1 stimulated the formation of calcified nodules, increased alkaline phosphatase activity, and enhanced the expression of osteogenic marker genes in the BMSCs from OP patients. Additionally, circPVT1 expression was negatively correlated with miR-30d-5p, and miR-30d-5p was negatively correlated with ITGB3 in OP patients. Mechanically, circPVT1 regulated the osteogenic differentiation potential of BMSCs by relieving the inhibition of miR-30d-5p on ITGB3 through the competitive endogenous RNA mechanism. CONCLUSION: Our study highlighted a circPVT1/miR-30d-5p/ITGB3 axis in regulating osteogenic differentiation potential of BMSCs from OP patients.

FUCA2 Is a Prognostic Biomarker and Correlated With an Immunosuppressive Microenvironment in Pan-Cancer.

Background: The expression of Fucosidase, alpha-L-2 (FUCA2) varies across tumors. However, its role in various tumor types and relationship with the tumor immune microenvironment (TIME) is poorly defined. Methods: We analyzed profiles of FUCA2 expression using datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Next, gene alteration, clinical characteristics and prognostic values of FUCA2 were elucidated based on TCGA pan-cancer data. This was followed by gene set enrichment analysis by R software. Relationships between FUCA2 expression and immune infiltration and immune-related genes were also evaluated. Moreover, the association of immune cell infiltration with FUCA2 expression was evaluated across three different sources of immune cell infiltration data, namely the TIMER online, ImmuCellAI databases, as well as a published study. In addition, MTT assays was also conducted to validate the oncogene role of FUCA2 in lung cancer cells. Results: FUCA2 was upregulated in most tumors, and this was significantly associated with poor survival rates. Gene set enrichment analysis uncovered that FUCA2 correlated with immune pathways in different tumor types. FUCA2 expression was positively related to tumor associated macrophages (TAMs), especially M2-like TAMs. Moreover, FUCA2 level showed a positive relationship with most immunosuppression genes, including programmed death-ligand 1 (PD-L1), transforming growth factor beta 1 (TGFB1), and interleukin-10 (IL10) in most cancer types. FUCA2 knockdown inhibited the cell viability in lung cancer cells. Conclusions: Our study reveals that FUCA2 is a potential oncogene and is indicative biomarker of a worse prognosis in pan-cancer. High FUCA2 expression may contribute to increased infiltration of TAMs and associates with an immunosuppressive microenvironment, providing a potential target for tumor therapy.

CircNRIP1 Encapsulated by Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Aggravates Osteosarcoma by Modulating the miR-532-3p/AKT3/PI3K/AKT Axis.

Emerging evidence indicates that extracellular vesicle (EV)-encapsulated circRNAs have the potential diagnostic and prognostic values for malignancies. However, the role of circNRIP1 in osteosarcoma remains unclear. We herein investigated the therapeutic potential of circNRIP1 delivered by bone marrow mesenchymal stem cell-derived EVs (BMSC-EVs) in osteosarcoma. The expression of circNRIP1 was examined in the clinical tissue samples of osteosarcoma patients, after which the downstream genes of circNRIP1 were bioinformatically predicted. Gain- and loss-of function assays were then performed in osteosarcoma cells with manipulation of circNRIP1 and miR-532-3p expression. EVs isolated from BMSCs were characterized and co-cultured with osteosarcoma cells to examine their effects on cell phenotypes, as reflected by CCK-8 and Transwell assays. Further, a mouse model of tumor xenografts was established for in vivo substantiation. circNRIP1 was upregulated in osteosarcoma tissues and cells. Overexpression of circNRIP1 promoted the proliferative, migratory, and invasive potential of osteosarcoma cells. Co-culture data showed that BMSC-EVs could transfer circNRIP1 into osteosarcoma cells where it competitively bound to miR-532-3p and weakened miR-532-3p's binding ability to AKT3. By this mechanism, the PI3K/AKT signaling pathway was activated and the malignant characteristics of osteosarcoma cells were stimulated. In vivo experimental results unveiled that circNRIP1-overexpressing BMSC-EVs in nude mice resulted in enhanced tumor growth. In conclusion, the BMSC-EV-enclosed circNRIP1 revealed a new molecular mechanism in the pathogenesis of osteosarcoma, which might provide a novel therapeutic target for osteosarcoma.

A novel GHR-ALK fusion gene in a patient with metastatic lung adenocarcinoma and its response to crizotinib: a case report.

Anaplastic lymphoma kinase (ALK) rearrangement occurs in approximately 5% of non-small cell lung cancers (NSCLCS), and EML4-ALK is the most commonly observed ALK fusion variant in NSCLC. However, growth hormone receptor (GHR) as the fusion partner for ALK and the clinical response to ALK tyrosine kinase inhibitors in patients with metastatic lung adenocarcinoma (LUAD) who carry the GHR-ALK variant have not been documented. This case describes a 63-year-old woman diagnosed with metastatic LUAD. Immunohistochemistry revealed positive ALK expression, and the patient was treated with crizotinib. After 3 weeks of treatment, the patient had a partial response. Because of treatment-related adverse events, the dose of crizotinib was reduced. After 3.7 months, computed tomography uncovered disease progression. Next-generation sequencing identified a novel GHR-ALK fusion in the plasma of the patient. The patient was treated again with crizotinib, but the disease progressed again 2 months later. Then, the patient received chemotherapy. She succumbed to her disease 11 months after the initial diagnosis. Our work provides evidence supporting the use of crizotinib in patients with metastatic LUAD harboring GHR-ALK.

Efficacy of Sorafenib Combined with Interventional Therapy on Primary Liver Cancer Patients and Its Effect on Serum AFP, VEGF, and GGT.

OBJECTIVE: To explore the efficacy of sorafenib combined with interventional therapy on primary liver cancer (PLC) patients and its effect on serum AFP, VEGF, and GGT. METHODS: 120 PLC patients admitted to our hospital from January 2016 to January 2020 were selected as the research object and divided into group A and group B according to the admission order, with 60 cases each. Interventional therapy was performed to both groups, and sorafenib was given to group A additionally to compare their treatment effect, survival, adverse reaction rate (ARR), and serum AFP, VEGF, and GGT levels. RESULTS: After treatment, group A obtained significantly higher objective remission rate (ORR) and disease control rate (DCR) (p < 0.05), higher one-year survival rate and two-year survival rate (p < 0.05), lower ARR of skin reactions, gastrointestinal reactions, hepatorenal reactions, and hyperbilirubinemia (p < 0.05), and lower serum AFP, VEGF, and GGT levels (p < 0.001). CONCLUSION: The combination of sorafenib and interventional therapy can inhibit the growth and migration of PLC, improve the immune function, prolong the survival period of patients, and lower ARR, so it should be promoted in practice.

IL1RN promotes osteoblastic differentiation via interacting with ITGB3 in osteoporosis.

The occurrence and progress of osteoporosis (OP) are partially caused by impaired osteoblast differentiation. Interleukin-I receptor antagonist (IL1RN) is an immune modulatory molecule that commonly functions by means of competing the binding site of IL-1R with IL-1. Although it was recently reported that IL1RN is involved in osteoblast differentiation, the role of IL1RN in osteogenesis remains unclear. In this work, we first investigated the expression pattern of IL1RN in ovariectomy mice and in vitro osteogenic induction of MC3T3-E1 and C3H10T1/2 cells. To verify the exact role of IL1RN in osteoblast differentiation, we established IL1RN-downregulated/upregulated cell lines. The results indicated that IL1RN was constantly expressed in MC3T3-E1 and C3H10T1/2 cells. Interestingly, an increase of IL1RN expression in osteoblasts occurred when osteoblasts were cultured in osteogenic medium (OM). As expected, silencing of IL1RN attenuated the osteogenic effect of OM, while IL1RN overexpression increased the osteogenic staining and promoted the expression of osteogenic markers, including alkaline phosphatase, osterix, and osteocalcin. In addition to evaluating the function of IL1RN in osteoblasts, we also investigated the molecular mechanism of the role of IL1RN in osteoblasts. We found that IL1RN interacts with integrin ß3 to activate ß-catenin signaling, which finally regulates osteoblast differentiation. Taken together, this study provides the framework that IL1RN, as a novel regulator of osteogenesis, may be a potential therapeutic target for the treatment of OP.

Correlation between pattern density and linewidth variation in silicon photonics waveguides.

We describe the correlation between the measured width of silicon waveguides fabricated with 193 nm lithography and the local pattern density of the mask layout. In the fabrication process, pattern density can affect the composition of the plasma in a dry etching process or the abrasion rate in a planarization step. Using an optical test circuit to extract waveguide width and thickness, we sampled 5841 sites over a fabricated wafer. Using this detailed sampling, we could establish the correlation between the linewidth and average pattern density around the test circuit, as a function of the radius of influence. We find that the intra-die systematic width variation correlates most with the pattern density within a radius of 200 µm, with a correlation coefficient of 0.57. No correlation between pattern density and the intra-die systematic thickness variation is observed. These findings can be used to predict photonic circuit yield or to optimize the circuit layout to minimize the effect of local pattern density.

Tolerant, broadband tunable 2 × 2 coupler circuit.

We propose a circuit design for a broadband tunable 2 × 2 waveguide coupler, consisting of a two-stage Mach-Zehnder interferometer with electro-optic phase shifters in each stage. We demonstrate that such design can be configured as a tunable coupler with arbitrary coupling ratio and with a uniform response over 50-nm spectral range around 1550 nm. The design is also tolerant to fabrication variations that affect the coupling ratios of the directional couplers.

Silicon ring resonators with a free spectral range robust to fabrication variations.

We propose a design method for silicon ring resonators (RRs) with a free spectral range (FSR) insensitive to fabrication variations. Two waveguide-core widths are used in the RR, with opposite signs of the group-index derivative with respect to the width. This results in cancellation of the width-dependent FSR changes. The systematic deviation of the realized width from the design width is determined and is used for calibrating the calculated relation of group index versus width. This enables a more accurate FSR value and well-aimed robust performance. We present two robust design examples. Experimental results match well with the predictions. For the deliberately introduced ±10 nm core-width change, the FSR variation of the robust designs is only about 30% of the value measured from the RR with a single core width. This design method can be used to improve the performance of photonic integrated circuits using multiple RRs. As the FSR of a RR is not easily tunable, the robust design is beneficial to applications where an accurate FSR is required, such as in microwave photonics.

Establishment of patient-derived tumor spheroids for non-small cell lung cancer.

The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. One of the reasons for this hampered progress has been a lack of in vitro models that would faithfully recapitulate the heterogeneity of tumors and response to treatment. In this study, surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Using a 3D patient-derived tumor spheroids culture system, our results demonstrate successful long-term expansion of primary NSCLC cells in vitro (> 120 days). Patient-derived tumor spheroid (PDS) cultures could be established with a success rate of 100% (3 out of 3 samples). Consistent with their growth in culture and their cancer type, many cells within the tumor spheroids were stained positive for Ki67 and thyroid transcription factor-1. The result of this study supports the establishment of an expandable 3D in vitro NSCLC model for drug screening, and enables the potential long term studies such as the establishment of drug resistant models.

Interferon regulatory factor 4 (IRF4) is overexpressed in human non­small cell lung cancer (NSCLC) and activates the Notch signaling pathway.

The transcription factor, interferon regulatory factor 4 (IRF4), serves an essential role in the regulation of immune responses, and has been reported to act as a diagnostic and prognostic marker for various hematological malignancies. The present study aimed to investigate whether IRF4 could exert effects on human non­small cell lung cancer (NSCLC) and to explore the underlying mechanism. The mRNA and protein expression of IRF4 was detected in NSCLC tissues using reverse­transcription quantitative polymerase chain reaction and western blotting, respectively. In the in vitro experiment, IRF4 expression was knocked down or overexpressed using lentivirus in human lung adenocarcinoma A549 and lung squamous cell carcinoma LC­AI cell lines. Cell proliferation and colony number were analyzed using MTT and colony formation assays, respectively. The expression levels of IRF4 mRNA and protein were significantly higher in NSCLC tissues (n=54) compared with that in adjacent non­tumor tissues. Similarly, the expression levels of Notch1 and Notch2 mRNA were significantly higher in NSCLC tissues. Furthermore, the expression level of IRF4 mRNA was positively correlated with the levels of Notch1 and Notch2 mRNA in NSCLC tissues. Consequently, using NSCLC cell lines, it was demonstrated that the knockdown of IRF4 expression significantly reduced the cell proliferation rate and colony formation, whereas IRF4­overexpression significantly increased them. Notably, the IRF4 knockdown significantly decreased the expression levels of Notch1 and Notch2 mRNA, and phosphorylated protein kinase B (AKT), whereas IRF4 overexpression resulted in the opposite. The results of the present study indicate that IRF4 is overexpressed and serves as a tumor promoter in human NSCLC, at least partially, through activating the Notch­Akt signaling pathway.

The tumor suppressor p53 regulates autophagosomal and lysosomal biogenesis in lung cancer cells by targeting transcription factor EB.

The cellular protein degradation system, such as proteasomal or autophagy-lysosomal system plays an important role in the pathogenesis of a variety of human diseases including cancer. Transcription factor EB (TFEB) is a master transcriptional factor in the regulation of autophagy-lysosome pathway (ALP), and it has multiple biological functions including protein degradation, cell homeostasis and cell survival. In the present study we show that the tumor suppressor p53 can regulate TFEB nuclear translocation and activity in lung cancer cells. We found p53 deletion or chemical inhibition of p53 using pifithrin-α could promote the translocation of TFEB from cytoplasm to the nucleus, thus increased the TFEB-mediated lysosomal and autophagosomal biogenesis in lung cancer cells. Moreover, re-expression of p53 could decrease the expression levels of TFEB-targeting genes involved in ALP, and knockdown of TFEB could abolish the effect of p53 on the regulation of ALP gene expression. Taken together, our data indicate that p53 affects ALP through regulating TFEB nuclear translocation in lung cancer cells. Importantly, our study reveals a critical link between two keys factors in tumourigenesis and autophagy, and suggests a potential important role of p53-TFEB signaling axis in lung cancer.

Increased soluble and membrane-bound PD-L1 contributes to immune regulation and disease progression in patients with tuberculous pleural effusion.

Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1, respectively) have been demonstrated to participate in the immune suppression of non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to immune regulation and disease progression in patients with pleural effusions remains unknown. The present study evaluated the levels of sPD-L1 and membrane-bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (n-TB n-M). Furthermore, selected T lymphocytes and cluster of differentiation (CD)14+ monocytes were co-cultured to investigate the potential effect of the PD-1/PD-L1 pathway in TPE. Levels of sPD-L1 and PD-L1 on CD14+ monocytes were increased in the TPE group, as compared with the MPE and n-TB n-M groups. Furthermore, sPD-L1 levels and the expression levels of PD-L1 on CD14+ monocytes were demonstrated to be positively correlated with interferon (IFN)-γ concentration in pleural effusions. Therefore, IFN-γ may increase the expression of PD-L1 on CD14+ monocytes in vitro. Cell counting kit-8 analysis demonstrated that anti-PD-L1 antibody was able to partially reverse the proliferation of T lymphocytes in the co-culture system. The results of the present study indicated that sPD-L1 or mPD-L1 are associated with the immune regulation and disease progression of TPE, and may serve as possible biomarkers of TPE. Furthermore, sPD-L1 and the PD-1/PD-L1 pathway of TPE may be associated with the Th1 immune response; therefore, an anti-PD-1/PD-L1 pathway suggests a potential immune therapy strategy for the treatment of TPE.