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.

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.

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.

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.

Low voltage and high resolution phase modulator based on blue phase liquid crystals with external compact optical system.

Liquid crystal phase modulators are emerging as a new technological advancement, since they can be used for a wide range of applications. To improve their performance, polymer stabilized blue phase liquid crystal (PS-BPLC) phase modulators with fast response time and accurate phase profile become a necessary. Here, we proposed a facile PS-BPLC phase modulator to achieve particularly low voltage and high resolution. By employing a specific external compact optical system setup, the driving voltage is reduced to 26.09V to obtain 2π phase change at the wavelength of 532 nm. An accurate numerical modeling is also conducted to provide a systematic investigation of the fringing electric field effect to the performance of high resolution PS-BPLC phase modulator. The wavefront distortion caused by the fringing electric field can be automatically compensated to generate accurate phase profile for fast response liquid crystal phase modulator. This work provides a new protocol to realize liquid crystal on silicon based fast response and high resolution phase modulator.

Dual-period tunable phase grating using polymer stabilized blue phase liquid crystal.

Dual-period tunable phase grating using polymer stabilized blue phase liquid crystal is demonstrated by controlling its driving scheme. High efficiencies of 35.3% for the small-period phase grating and 28.7% for the large-period phase grating have been achieved because of the rectangular-like phase profile which shows good agreement with the simulation results. The diffraction angle can be alternatively tuned, as well as the diffraction efficiency. Moreover, this device also possesses polarization independency and fast response with a rise time of 826 µs and a decay time of 1.143 ms which shows great potential for diffractive optics.

Investigation of fringing electric field effect on high-resolution blue phase liquid crystal spatial light modulator.

The fringing electric field effect which determines the performance of a high-resolution blue phase liquid crystal spatial light modulator (BPLC-SLM) is investigated by numerical modeling. The BPLC-SLM is polarization-dependent due to the transverse electric field component. The physical mechanism of the phase profile properties for different polarization states is analyzed. General design issues related to the BPLC-SLM configuration and phase profile properties are discussed. Notably, the material parameters and cell gap thickness are both optimized to obtain a low operation voltage (V2π=26.07 V). This work provides fundamental understanding for the feasibility of low operation voltage and high spatial resolution BPLC-SLM.

[Effects of soluble programmed death ligand 1 on regulating the proliferation of T lymphocytes and its mechanism].

OBJECTIVE: To explore the effects of soluble programmed death ligand 1 (sPD-L1) on the proliferation of T lymphocytes and its mechanism. METHODS: T lymphocytes were isolated from healthy human peripheral blood and activated by phytohemagglutinin (PHA). The experiment had group A: resting T lymphocytes, group B: activated T lymphocytes, group C: activated T lymphocytes+sPD-L1Ig, group D: activated T lymphocytes+sPD-L1Ig+membrance-bound immunoglobulin (mIgG) and group E: activated T lymphocytes+sPD-L1Ig+anti-PD-L1 antibody (2H11). The absorbance value (A) of T lymphocytes in each group was measured by cell counting kit (CCK-8). The cell cycle and apoptosis of T lymphocytes induced by sPD-L1 were measured by flow cytometry. And the phosphorylation level of programmed death 1 (PD-1) signaling motif tyrosine was measured by Western blot. Furthermore, the amounts of signal adaptor molecule Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and SHP-2 were quantified by immunoprecipitation. And the exciting mechanism of sPD-L1 was explored for PD-1 inhibitory signals. RESULTS: CCK-8 study showed that A values in each group were 0.42 ± 0.03, 1.20 ± 0.06, 0.87 ± 0.05, 0.78 ± 0.05 and 1.11 ± 0.09 respectively when the concentration of sPD-L1Ig was 250 ng/ml. The proliferation of T lymphocytes in group C significantly decreased compared with group B (t = 3.946, P = 0.017) while group E significantly increased compared with group D (t = 3.139, P = 0.035). The percentage of cell number in G1 phase of the above-mentioned 5 groups were (94.49 ± 0.50)%, (79.22 ± 0.50)%, (89.62 ± 0.33)%, (92.89 ± 0.80)% and (87.94 ± 0.87)% respectively and group C significantly increased compared with group B (t = 17.310, P < 0.001). The apoptotic rate of the above-mentioned five groups were (35.77 ± 1.82)%, (35.20 ± 2.70)%, (62.77 ± 0.24)%, (64.47 ± 0.44)% and (36.80 ± 3.53)% respectively. And apoptotic rate in group C significantly increased compared with group B (t = 10.160, P = 0.001) while group E significantly decreased compared with group D (t = 7.790, P = 0.002). The expressions of SHP-1 and SHP-2 showed no inter-group difference (all P > 0.05). However, the expressions of p-SHP-1 and p-SHP-2 in group C was higher than those in group B (t = 10.790, P < 0.001; t = 13.051, P < 0.001) while the expression of p-SHP-1 decreased in group E compared with group D (t = 3.361, P = 0.028). CONCLUSIONS: Soluble PD-L1 can effectively inhibit the proliferation of T lymphocytes. The phosphorylation of SHP-1 and SHP-2 contributes to the inhibitory signaling of PD-1/sPD-L1 pathway. And anti-PD-L1 blocking antibody may partially restore the proliferation of T lymphocytes through a down-regulated expression of p-SHP-1..

[Level of soluble programmed death ligand 1 in pleural effusion and peripheral blood of patients with tuberculous pleural effusion and its clinical implications].

OBJECTIVE: To explore the level of soluble programmed death ligand 1 (sPD-L1) in pleural effusion and peripheral blood of patients with tuberculous pleural effusion (TPE) and elucidate its clinical implications. METHODS: Patients with newly diagnosed pleural effusion at the Second Affiliated Hospital of Soochow University from June 2012 to March 2013 were enrolled and divided into 3 groups of TPE, malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (non-TPE non-MPE) according to the nature of pleural effusion. The level of sPD-L1 in pleural effusion and peripheral blood was analyzed by enzyme linked immunosorbent assay (ELISA) kit. Flow cytometry was used to detect the changes of immune cell subsets in pleural effusion. And the gene expressions of programmed death ligand 1 (PD-L1) and matrix metalloproteinase-3 (MMP-3) were detected in different effusions by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: A total of 77 newly diagnosed patients with pleural effusion were enrolled, 24 patients with TPE, 39 patients with MPE, 14 patients with non-TPE non-MPE. The level of sPD-L1 in TPE was higher than that in MPE and non-TPE non-MPE (4.2 (2.6-6.3), 1.4 (0.8-2.1), 1.8 (1.2-2.6) µg/L, P < 0.001). No significant difference existed in the levels of sPD-L1 in peripheral blood samples (P = 0.811). The average content of sPD-L1 in pleural effusion in all patients was statistically higher than that in peripheral blood (2.0 (1.4-3.7), 1.5 (1.0-2.0) µg/L, P = 0.004). The proportion of CD8 subset, PD-L1 on CD14(+) monocytes and the mRNA level of PD-L1, MMP-3 in TPE were higher than in MPE and non-TPE non-MPE (P = 0.001, P < 0.001, P < 0.001), and the mRNA level of PD-L1 in TPE was positively correlated with the level of MMP-3 (r = 0.887, P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that sPD-L1 had a sensitivity of 82.6%, a specificity of 83.8% and an area under curve (AUC) of 0.854 for differential diagnosis of TPE from other conditions. Combinations of sPD-L1, PD-L1 on CD14(+) monocytes and adenosine deaminase (ADA) measurements further increased the sensitivity up to 91.3%, specificity up to 89.2% and AUC up to 0.989. CONCLUSION: The elevated expression of sPD-L1 in tuberculous pleural effusion may aid the diagnosis of TPE.

[Effect of cisplatin alone or combined with monoclonal anti-programmed death ligand-1 antibody on lung adenocarcinoma cell line SPCA-1 and T lymphocytes].

OBJECTIVE: To observe the effect of cisplatin alone or combined with anti-programmed death ligand 1 monoclonal antibody (anti-PD-L1 mAb) on the co-culture system of lung adenocarcinoma SPCA-1 cells and T lymphocytes, and therefore to study the immunotherapeutic effect of anti-PD-L1 mAb on lung cancer. METHODS: Human adenocarcinoma SPCA-1 cell line was selected by flow cytometry (FCM) due to its high expression of membranous programmed death ligand-1 (PD-L1). The concentration of cisplatin was determined by CCK-8 method depending on the inhibition rate of SPCA-1 cell, which was set to less-than-or-equal-to 20% (IC20). After treatment with different concentrations of cisplatin, cell proliferation (A value) of SPCA-1 cells and T lymphocytes were detected by CCK-8 method and cell cycle of SPCA-1 cells and cell apoptosis of T lymphocytes were analyzed using PI staining. Treated with different concentrations of cisplatin alone or in combination with anti-PD-L1, T lymphocyte proliferation in co-culture system was determined by CCK-8 method, and cytokines such as IFN (interferon)-γ, IL-2, IL-10 and TNF-α were detected with enzyme linked immunosorbent assay (ELISA) method. RESULTS: The IC20 of cisplatin on SPCA-1 cells was ≤ 0.78 mg/L. The proliferation of SPCA-1 cells were inhibited with different concentrations of cisplatin in a concentration-dependent manner (0.78∼12.5 mg/L) (P < 0.001). Compared with the group treated with high-dose of cisplatin (12.5 mg/L), the proliferation of T lymphocytes treated with low-dose of cisplatin (0.78 mg/L) was higher (t = 3.508, P < 0.05) and the number of late apoptotic and dead T lymphocytes in the co-culture system was reduced (t = 17.55, P < 0.001). Compared with the group of co-culture system, cisplatin (0.78 mg/L) combined with anti-PD-L1 (1.5 mg/L) significantly enhanced the proliferation of T lymphocytes in the co-culture system (t = 4.419, P < 0.01). Also, the levels of T helper cell type-1 (Th1) cytokines such as IFN-γ, IL-2 and TNF-α were up-regulated (t = 25.79-55.15, P < 0.01) and the T helper cell type-2 (Th2) cytokine IL-10 was down-regulated (t = 18.38, P < 0.01). CONCLUSION: Low-dose of cisplatin combined with anti-PD-L1 could effectively promote the proliferation of T lymphocytes in the microenvironment and increase the secretion of Th1 type cytokines. This may reduce the toxic effect of high-dose antineoplastic agents on immune cells and help eradication of tumor cells.

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.

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.

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.

[Effect of soluble PD-L1 released by lung cancer cells in regulating the function of T lymphocytes].

OBJECTIVE: To explore the expression of soluble programmed death ligand-1 on lung cancer cells and to clarify its biological function through PD-1/PD-L1 pathway in regulating the function of T lymphocytes. METHODS: Labeled monoclonal antibody and flow cytometry were used to analyze the expression of PD-L1 and its receptor PD-l on lung cancer cells and human T lymphocytes, respectively. The level of sPD-L1 in the supernatant of lung cancer cells was determined with an ELISA kit. The inhibition of proliferation of T lymphocytes by mPD-L1 and sPD-L1 was studied using CCK-8 incorporation. RESULTS: Low or no expression [(16.08 ± 2.28)%] of PD-1 was found on resting T lymphocytes from human peripheral blood with flow cytometry, but up-regulated expression of PD-1 [(78.06 ± 7.21)%] was found on the surface of activated T lymphocytes. Soluble PD-L1 was found in supernatant of some lung cancer cell lines, such as H1299, HO8910, SPCA-1, H460, H446 cells, with PD-L1 expressing on their cell surface [(78.34 ± 10.25)%, (68.17 ± 11.56)%, (45.32 ± 7.98)%, (47.52 ± 9.62)% and (40.95 ± 8.56)%, respectively], but very low expression on A549 cells [(16.02 ± 6.28)%]. The level of mPD-L1 on H1299 cells was highest [(78.34 ± 10.25)%], compared with HO8910 cells (68.17 ± 11.56)%, SPCA-1 cells (45.32 ± 7.98)%, H446 cells (40.95 ± 8.56)%, and H460 cells (47.52 ± 9.62)%. At the same time, the sPD-L1 level on H1299 cells was low [(0.17 ± 0.01) ng/ml], compared with HO8910 cells (0.30 ± 0.03) ng/ml, SPCA-1cells (0.59 ± 0.03) ng/ml, H446 cells (0.34 ± 0.02) ng/ml, and H460 cells (0.57 ± 0.03) ng/ml, but not expressed on A549 cells. PD-L1 expressing H1299 cells inhibited the proliferation of T lymphocytes in the co-culture system. Supernatant of the cultured PD-L1(+) lung cancer cells also inhibited T cell proliferation. Anti-human PD-L1 blocking antibody could partly restore the proliferation capacity of T lymphocytes. CONCLUSIONS: Membrane-bound PD-L1 and soluble PD-L1 released from lung cancer cells can effectively inhibit the proliferation of T lymphocytes in mixed culture system and down-regulate cell-mediated immunity in vitro. This may lead to inactivation of tumor antigen-specific T cells and immune escape of lung cancer cells.

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.

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.

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.

[The level of soluble programmed death-1 in peripheral blood of patients with lung cancer and its clinical implications].

OBJECTIVE: To analyze the expression of soluble programmed death-1 ligand 1 (sPD-L1) in the serum of patients with lung cancer and to explore its biological and clinical implications. METHODS: Fifty-five male and twenty-six female lung cancer patients ages 34 to 87 years (mean age 65 ± 6) were selected from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from June 2009 to March 2011. All lung cancer patients were newly-diagnosed, treatment-free and confirmed by histopathology or cytopathology. Eight-eight healthy volunteers matching in sex and age from the Healthcare Center of the hospital were also enrolled as controls. The sPD-L1 protein expression in serum was determined by Western blot and self-developed ELISA kit. Fluorescence-labeled monoclonal antibody and cytometry were used to examine changes in lymphocyte subsets in the peripheral blood of lung cancer patients and healthy controls. RESULTS: A higher level of sPD-L1 level in the lung cancer patients [1.6 (0.7 - 7.8) µg/L] was found compared to the control group [0.9 (0.4 - 3.7) µg/L] (P < 0.001). High expression of sPD-L1 in the lung cancer patients was closely correlated to lymph node metastasis and the extent of distant metastasis (χ(2) = 5.636, P < 0.05; χ(2) = 4.601, P < 0.05). The sPD-L1 level in lung cancer patients with objective response to treatment (complete response + partial response) was 2.7 (1.6 - 7.0) µg/L and 1.1 (0.8 - 1.7) µg/L before and after treatment, respectively (P < 0.01). The level of sPD-L1 with progression disease was 1.9 (1.3 - 8.5 µg/L) which was significantly increased compared to the baseline level 1.4 (0.8 - 2.2) µg/L (P < 0.01). Additionally, abnormal changes of T and B lymphocytes and their subsets were found, with a significant decrease of CD(8)(+) T lymphocytes (P < 0.05) and a rise in CD(4)/CD(8) ratio (P < 0.05). Further double-labeling study showed increased percentages of CD(4)(+)PD-1(+) T lymphocytes and CD(8)(+)PD-1(+) T lymphocytes (P < 0.05). CONCLUSIONS: The elevated expression of sPD-L1 in lung cancer patients was closely related to lung cancer staging, metastasis and clinical response. sPD-L1 may become a predictive marker and an important anti-tumor target in individualized treatment of lung cancer.

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.