Abstract Background Radial endobronchial ultrasound with a guide sheath for transbronchial biopsy (EBUS-GS-TBB) can be considered for diagnosing peripheral pulmonary lesions (PPLs) with fewer complications in patients with emphysema. However, the utility and safety of bronchoscopy for PPLs in the proximity of emphysema-area lesions remain unclear. The aim of this study was to assess the efficacy and complications of the initial diagnostic procedure of bronchoscopy with EBUS-GS-TBB according to the proximity of PPLs to emphysema areas, along with factors affecting the successful diagnostic yield for PPLs, and to identify the feasibility of molecular and genetic testing using EBUS-GS-TBB-obtained tumor samples. Methods The medical records of 278 consecutive patients with PPLs who underwent EBUS-GS-TBB without X-ray fluoroscopy guidance were screened. We compared PPLs with emphysema in such lesions. PPLs with emphysema were divided into two groups: PPLs located in non-emphysema areas and those inside or near emphysema areas. Results This study included 84 patients with emphysema (non-emphysema area group = 46; inside or near emphysema area group = 38). The diagnostic yield was significantly higher for PPLs located in non-emphysema areas than for PPLs inside or near emphysema areas (82.6% vs. 52.6%, p = 0.013). Multivariate analysis revealed that PPLs located in non-emphysema areas (odds ratio = 5.614) and EBUS images within lesions were significant factors affecting diagnostic yield. Further, the utility of EBUS-GS-TBB for PPLs based on the proximity of PPLs to emphysema-area lesions in patients with emphysema is safety. Conclusions In patients with emphysema, the positional relation of PPLs to emphysema lesions and EBUS images within lesions were important factors affecting successful diagnosis using EBUS-GS-TBB.

Objective: To evaluate the efficacy and safety of photobiomodulation therapy (PBMT) in the treatment of diabetic patients with refractory wound.Background: Refractory wound is one of the most challenging clinical complications of diabetes mellitus. Studies have shown that PBMT can promote wound healing in many ways.Methods: We reported a 55-year-old male patient with refractory diabetic wound after secretory carcinoma of the parotid gland surgery responding to 810 nm laser.Results: After PBMT, the refractory diabetic wound healed gradually without adverse events. During follow-up 5-years, the healed wound remained stable and showed no signs of recurrence.Conclusions: PBMT can be potentially considered as a therapeutic method in diabetic patients with refractory diabetic wound.

Dental implantation, when performed immediately after tooth extraction, simplifies the treatment procedure, resulting in satisfaction for dentists and patients. Dental implants with nanotopography surface modification have been used to promote osseointegration immediately after implantation. We compared two different nanotopography surface implants on the effects of osseointegration immediately after tooth extraction: TiO 2 nanotubes (NT-TiO 2 ) fabricated by anodization and Sr-loaded nanotopography Ti (NT-Sr) formed via magnetron sputtering technology. Sr-loaded nanotextured Ti nanotubes (NT-Sr) were fabricated via magnetron sputtering using 99.99% SrTiO 3 as the sputtering target. TiO 2 nanotubes (NT-TiO 2 ) were fabricated by anodization in 0.5 wt% hydrofluoric acid (HF). After the surface topography, hydrophilicity, chemical components, and interface bonding strength were analyzed, two different nano-topographies were applied for in vivo cellular activity evaluation. Subsequently, the implants with NT-Sr and NT-TiO 2 surfaces were inserted into the fresh socket immediately after tooth extraction. Radiological scanning, histological analysis, and biomechanical tests were carried out to investigate implant osseointegration. The results showed that nanotubes with diameters of 15–80 nm were distributed on the NT-TiO 2 surface, while the NT-Sr group showed 20–40 nm nanoparticles deposited on the surface. Compared to NT-Sr, the NT-TiO 2 surface possessed better hydrophilicity and favorable cellular adhesion and proliferation. The NT-Sr surface possessed greater interfacial bonding strength than the NT-TiO 2 group, and greater bone formation, higher bone-to-implant contact (BIC%), and maximum pull-out force were observed in the NT-Sr group. The above results indicated that although the NT-TiO 2 surface showed favorable in vitro bioactivity, the NT-Sr surface, with higher interface bonding strength, showed better in vitro osteogenesis, and would be more favorable for immediate implantation.

Background Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death. Malignant pleural effusion (MPE) is a special microenvironment for lung cancer metastasis. Alternative splicing, which is regulated by splicing factors, affects the expression of most genes and influences carcinogenesis and metastasis. Methods mRNA-seq data and alternative splicing events in lung adenocarcinoma (LUAD) were obtained from The Cancer Genome Atlas (TCGA). A risk model was generated by Cox regression analyses and LASSO regression. Cell isolation and flow cytometry were used to identify B cells. Results We systematically analyzed the splicing factors, alternative splicing events, clinical characteristics, and immunologic features of LUAD in the TCGA cohort. A risk signature based on 23 alternative splicing events was established and identified as an independent prognosis factor in LUAD. Among all patients, the risk signature showed a better prognostic value in metastatic patients. By single-sample gene set enrichment analysis, we found that among tumor-infiltrating lymphocytes, B cells were most significantly correlated to the risk score. Furthermore, we investigated the classification and function of B cells in MPE, a metastatic microenvironment of LUAD, and found that regulatory B cells might participate in the regulation of the immune microenvironment of MPE through antigen presentation and promotion of regulatory T cell differentiation. Conclusions We evaluated the prognostic value of alternative splicing events in LUAD and metastatic LUAD. We found that regulatory B cells had the function of antigen presentation, inhibited naïve T cells from differentiating into Th1 cells, and promoted Treg differentiation in LUAD patients with MPE.

IntroductionTumor-associated macrophages are one of the key components of the tumor microenvironment. The immunomodulatory activity and function of macrophages in malignant pleural effusion (MPE), a special tumor metastasis microenvironment, have not been clearly defined.MethodsMPE-based single-cell RNA sequencing data was used to characterize macrophages. Subsequently, the regulatory effect of macrophages and their secreted exosomes on T cells was verified by experiments. Next, miRNA microarray was used to analyze differentially expressed miRNAs in MPE and benign pleural effusion, and data from The Cancer Genome Atlas (TCGA) was used to evaluate the correlation between miRNAs and patient survival.ResultsSingle-cell RNA sequencing data showed macrophages were mainly M2 polarized in MPE and had higher exosome secretion function compared with those in blood. We found that exosomes released from macrophages could promote the differentiation of naïve T cells into Treg cells in MPE. We detected differential expression miRNAs in macrophage-derived exosomes between MPE and benign pleural effusion by miRNA microarray and found that miR-4443 was significantly overexpressed in MPE exosomes. Gene functional enrichment analysis showed that the target genes of miR-4443 were involved in the regulation of protein kinase B signaling and lipid biosynthetic process.ConclusionsTaken together, these results reveal that exosomes mediate the intercellular communication between macrophages and T cells, yielding an immunosuppressive environment for MPE. miR-4443 expressed by macrophages, but not total miR-4443, might serve as a prognostic marker in patients with metastatic lung cancer.

BACKGROUND:The current neck management for early oral squamous cell carcinoma (OSCC) has always been a controversial issue. A comprehensive model is necessary for predicting an individual's metastasis risk and appropriate patient counseling.METHODS:A nomogram for predicting 2-year LNM in patients with cT1-2N0 OSCC was developed and validated using clinicopathological data from 642 patients from 2000 to 2018 in four hospitals, China.RESULTS:Three variables (pathology grade, depth of invasion, tumor-infiltrating lymphocytes) were included in nomogram. C-indices were 0.826 (95% CI: 0.786-0.866) and 0.726 (95% CI: 0.653-0.780) in the internal and external validation. Kaplan-Meier method found the 2-year LNM rate of high-risk group (35.8%) was much higher than that of the low-risk group (14.5%). The nomogram model has an advantage over the 8th AJCC TNM stage in predicting the individual 2-year LNM probability for early OSCC.CONCLUSION:Patients with low-risk nomogram score may receive neck observation; those with high-risk score should receive END.

Background Medical thoracoscopy (MT) is recommended in patients with undiagnosed exudative pleural effusion and offers a degree of diagnostic sensitivity for pleural malignancy. However, not all patients who undergo MT receive an exact diagnosis. Our previous investigation from 2014 summarized the long-term outcomes of these patients with nonspecific pleurisy (NSP); now, we offer updated data with the goal of refining our conclusions. Methods Between July 2005 and August 2018, MT with pleural biopsies were performed in a total of 1,254 patients with undiagnosed pleural effusions. One hundred fifty-four patients diagnosed with NSP with available follow-up data were included in the present study, and their medical records were reviewed. Results A total of 154 patients were included in this study with a mean follow-up duration of 61.5 ± 43.7 months (range: 1–180 months). No specific diagnosis was established in 67 (43.5%) of the patients. Nineteen patients (12.3%) were subsequently diagnosed with pleural malignancies. Sixty-eight patients (44.2%) were diagnosed with benign diseases. Findings of pleural nodules or plaques during MT and the recurrence of pleural effusion were associated with malignant disease. Conclusions Although most NSP patients received a diagnosis of a benign disease, malignant disease was still a possibility, especially in those patients with nodules or plaques as noted on the MT and a recurrence of pleural effusion. One year of clinical follow-up for NSP patients is likely sufficient. These updated results further confirm our previous study’s conclusions.

Pleural effusion (PE) is prevalent in unselected "real-life" populations of multiple myeloma (MM). However, its prognostic value on MM is currently elusive. This study aimed to explore the role of PE on MM prognosis and to develop a novel prognostic nomogram for a cohort of Chinese patients with MM. Patients diagnosed with MM form 2000 through 2017 were retrospectively enrolled. PE was evaluated by chest computed tomography (CT) scans. Independent predictors of overall survival (OS) were identified using a multivariable Cox regression model performed on variables selected by the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram was constructed based on these variables. The concordance index (C-index) and the calibration curve were used to evaluate the predictive performance of the nomogram. Among 861 patients analyzed, 368 patients developed PE. Multivariate cox regression and restricted mean survival time (RMST) analyses revealed that patients with PE experienced worse OS vs. patients without PE. A nomogram predictive of OS was constructed using PE, plasma cell proportion, international staging system (ISS) stage, Charlson comorbidity index (CCI), 1q21 gain, and autologous hematopoietic stem cell transplantation (HSCT). The nomogram showed satisfactory discrimination in the derivation cohort (C-index=0.729) and the validation cohort (C-index=0.684), outperforming the Durie-Salmon (DS) and ISS staging systems. Moreover, the nomogram accurately classified patients into two distinct high- and low-risk groups. PE is frequently encountered in the disease course for MM patients. We derivated and validated a novel nomogram for MM based on PE, outperforming the DS/ISS staging systems.

OBJECTIVE The purpose of this study was to explore the necessity of adjuvant radiotherapy for well-differentiated pT3-4aN0M0 OSCC without other negative features histologically. PATIENTS AND METHODS This is a double-center, ambispective cohort study enrolling 250 patients with well-differentiated pT3-4aN0M0 OSCC. RESULTS 250 patients were enrolled in the double-center study, 155(62.0%) men and 95 (38.0%) women, and the mean age was 60.1 ± 11.1 years. T staging was classified as follows: T3 (n=99, 39.6%), and T4a (n=151, 60.4%). Kaplan-Meier analysis showed that there was no significant difference in the DSS between patients who received adjuvant radiotherapy (72.2%) and those who did not (77.4%) (p=0.615). Specifically, no significant difference was found in the DSS of pT3N0M0 or pT4aN0M0 patients who received adjuvant radiotherapy compared with those who did not (pT3N0M0: 71.9% vs. 75.8%, p=0.993; pT4aN0M0: 72.4% vs. 78.5%, p=0.491). The Cox proportional hazards regression models showed that no factor was independent prognostic factor for pT3-4aN0M0 patients, or pT3N0M0 subgroup or pT4aN0M0 subgroup in DSS. And no independent prognostic factor was found for the surgery alone subgroup and adjuvant radiotherapy subgroup. CONCLUSIONS The results showed that adjuvant radiotherapy did not obviously improve the prognosis of pT3-4aN0M0 well-differentiated OSCC without other negative features.

The role of IL‐10 in malignant pleural effusion (MPE) remains unknown. By using murine MPE models, we observed that an increase in pleural IL‐10 was a significant predictor of increased risk of death. We noted that TH1‐ and TH17‐cell content in MPE was higher in IL‐10–/– mice than in WT mice, and IL‐10 deficiency promoted differentiation into TH1 but not into TH17 cells. A higher fraction of TH1 and TH17 cells in the MPE of IL‐10–/– mice expressed CXCR3 compared with WT mice. We also demonstrated that Lewis lung cancer and colon adenocarcinoma cells secreted large amounts of CXCL10, a ligand of CXCR3, which induced the migration of TH1 and TH17 cells into the MPE, and IFN‐γ could promote this signaling cascade. Furthermore, intrapleural injection of mice with CXCL10‐deficient tumor cells led to decreased TH1‐ and TH17‐cell content in MPE, increased MPE volume, and reduced survival of MPE‐bearing mice. Taken together, we demonstrated that IL‐10 deficiency promoted T‐cell differentiation into TH1 cells and upregulated the CXCR3‐CXCL10 signaling pathway that recruits TH1 and TH17 cells into MPE, ultimately resulting in decreased MPE formation and longer survival time of mice‐bearing MPE.

Abstract Background: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM. Methods: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated. Results: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64–0.72), 0.91 (95% CI: 0.86–0.94), 7.8 (95% CI: 5.0–12.0), 0.35 (95% CI: 0.31–0.40), and 22 (95% CI: 14–35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72–0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias. Conclusion: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.

Although some parameters of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG) and computed tomography (PET-CT) are somehow helpful in differentiating malignant pleural effusion (MPE) from benign effusions, no individual parameter offers sufficient evidence for its implementation in the clinical practice. The aim of this study was to establish the diagnostic accuracy of a scoring system based on PET-CT (the PET-CT score) in diagnosing MPE.

Abstract Background Only few studies have reported the association between bronchiectasis and mortality in patients with Chronic Obstructive Pulmonary Disease (COPD) and the results were controversial. This study aimed at assessing the prognostic influence of bronchiectasis on COPD patients and comparing differences of prognostic influence of different types of bronchiectasis on COPD patients. Patients and methods This study enrolled patients hospitalized for COPD exacerbation between 2013 and 2014. Bronchiectasis was identified on high-resolution computed tomography (HRCT) within 2 years prior to this hospitalization due to COPD exacerbation and Smith score was used to determine the extent of bronchiectasis. Clinical data were obtained from electronic inpatient medical record. The survival data were obtained through telephone follow-up or electronic medical record. Cox regression analysis was used to assess the prognostic influence of bronchiectasis on COPD patients. Results 748 COPD patients were included in this study. 318 patients were identified to have bronchiectasis. During a median follow-up time of 46 months, 624 COPD patients completed follow-up. There were 210 deaths, 112 of whom were comorbid bronchiectasis patients. Comorbid bronchiectasis patients revealed higher mortality than without bronchiectasis patients in 3 years and the whole follow-up, other than in hospital, 1 year and 2 years. The presence of bronchiectasis and its severity were independently associated with increased mortality of COPD patients. The presence of cystic/varicose bronchiectasis revealed higher mortality than cylindrical bronchiectasis and was independently associated with increased mortality of comorbid bronchiectasis patients. Conclusions The presence of bronchiectasis and its severity were independently associated with increased risk of all-cause mortality and mainly affected the long-term mortality of COPD patients. The presence of cystic/varicose bronchiectasis predicted higher death risk of COPD patients.

Malignant pleural mesothelioma (MPM) is marked by its difficult diagnosis and poor prognosis. Medical thoracoscopy (MT) is an effective and safe procedure for the diagnosis of exudative pleural effusions and many factors associated with poor prognosis of MPM. We conducted this study to investigate the value of MT for diagnosing of MPM and to identify prognostic factors for MPM patients.

In the present study, we were prompted to investigate the effect of NO signaling on the formation of malignant pleural effusion (MPE) and determined whether NO affects Th1/Th17 response in MPE. The development of MPE and survival of MPE mice were compared between wild-type and NOS2?/? mice. The effect of NOS2 on vascular permeability of pleura and differentiation of Th1 and Th17 in MPE was also explored. Our current data show that production of NO is significantly enhanced in MPE as compared with peripheral circulation, and that nitric oxide synthase-2 (NOS2) deficiency increases pleural vascular permeability and thus promotes the development of MPE, and reduces the survival of mice bearing MPE. NOS2 deficiency inhibits Th1 cell differentiation and promotes Th17 cell differentiation. Our data provide the first evidence that NO inhibits MPE formation by inhibiting fluid extravasation into the pleural space and by promoting Th1 cell differentiation and suppressing Th17 cell differentiation. Overall, our results shed light on the mechanisms by which NO suppresses MPE formation, providing a promising therapeutic strategy in the management of MPE.

Inflammatory signaling networks between tumor cells and immune cells contribute to the development of malignant pleural effusion (MPE). B cells have been found in MPE; however, little is known about their roles there. In the present study, by using mouse MPE models, we noted that although the total B cells in MPE were decreased as compared with the corresponding blood and spleen, the percentage of activated naïve B cells expressing higher levels of CD80, CD86, myosin heavy chain-II, CD44, CD69, and programmed cell death-ligand 1 (PD-L1) molecules were increased in wild-type mouse MPE. Compared with wild-type mice, decreased T helper (TH)1 cells and increased TH17 cells were present in B cell-deficient mouse MPE, which paralleled to the reduced MPE volume and longer survival time. Adoptive transfer of activated naïve B cells into B cell-deficient mice was able to increase TH1 cells and decrease TH17 cells in MPE and shorten the survival of mice bearing MPE. Furthermore, we demonstrated that activated naïve B cells inhibited TH17-cell expansion via the PD-1/PD-L1 pathway and promoted naïve CD4+ T-cell differentiation into TH1/TH17 cells through secreting IL-27/IL-6 independent of the PD-1/PD-L1 pathway. Collectively, our data uncovered a mechanism by which naïve B cells promote MPE formation by regulating TH1/TH17 cell responses, making these B cells an attractive target for therapeutic intervention in the fight against cancer.

Background: Pleural effusion (PE) drainage can relieve the symptoms of dyspnea; however, details of the resulting hemodynamic changes remain undefined. Methods: Subjects older than 12 years with massive PE requiring pleural drainage were included in this study. Hemodynamic parameters were collected using transthoracic echocardiography at pre-drainage, immediately post-drainage, and 24 h after drainage. Results: We enrolled 47subjects in this prospective study from June 9, 2015 to September 18, 2016 in Beijing Chaoyang Hospital and 28 subjects were analyzed finally. Draining large-volume PE led to a progressive increase in left ventricular end-diastolic volume index, left atrial volume index, right ventricular area, right atrial area, left ventricular ejection fraction, stroke volume, and tricuspid annular plane systolic excursion, both immediately (P<0.05) and 24 h after drainage (P<0.05). The cardiac diastolic measurement ratios of early-transmitral flow velocity to diastolic mitral annular velocity and myocardial performance index decreased significantly following drainage (P<0.05). More parameters were influenced by left-sided PE drainage. The correlation between effusion volume and changes in echocardiographic measurements was not statistically significant. Conclusions: Improved preload, and systolic and diastolic function is pivotal for hemodynamic change after draining large PE volumes. Subjects experienced improved cardiac hemodynamics following PE drainage, underlining the beneficial therapeutic and subjective effects.

BackgroundAccurate differentiating diagnosis is essential for choosing treatment for exudative pleural effusions.ObjectiveTo establish the diagnostic accuracy of interleukin 27 for tuberculous pleural effusion (TPE).MethodsFirst, the concentrations of pleural interleukin 27, interferon-gamma and adenosine deaminase were compared between 51 patients with TPE and 103 with non-TPEs (Beijing cohort), and their diagnostic values were evaluated. These were further verified in another independent population (Wuhan cohort, n=120). In the second part of the study, we performed a meta-analysis.ResultsWith a cut-off value of 591.4 ng/L in the Beijing cohort, the area under the curve, sensitivity, specificity, positive predictive value and negative predictive value of interleukin 27 to diagnose TPE were 0.983 (95% CI 0.947 to 0.997), 96.1% (86.5% to 99.5%), 99.0% (94.7% to 100%), 98.0 (89.4 to 99.9) and 98.1 (93.3 to 99.8), respectively. Excellent diagnostic accuracy of interleukin 27 was also found in the Wuhan cohort and was further confirmed in the meta-analysis. The diagnostic performance of interleukin 27 was comparable to that of interferon-gamma and was more accurate than that of adenosine deaminase. Since the post-test probability of a negative result was always <0.1%, a negative test was considered to exclude TPE in all tuberculosis prevalence settings.ConclusionsInterleukin 27 can be used to diagnose TPE in a high prevalence setting, and a negative result can also be reliably used to rule out TPE in all prevalence settings.

BACKGROUND:No data on the incidence of pleural effusion (PE) in Chinese patients with pulmonary embolism are available to date. The aim of the current study was to investigate the frequency of PE in a Chinese population of patients with pulmonary embolism.METHODS:This was a retrospective observational single-center study. All data of computed tomography pulmonary angiography (CTPA) performed over 6-year period on adult patients with clinically suspected pulmonary embolism were analyzed.RESULTS:From January 2008 until December 2013, PE was identified in 423 of 3141 patients (13.5%) with clinically suspected pulmonary embolism who underwent CTPA. The incidence of PE in patients with pulmonary embolism (19.9%) was significantly higher than in those without embolism (9.4%) (P < 0.001). Majority of PEs in pulmonary embolism patients were small to moderate and were unilateral. The locations of emboli and the numbers of arteries involved, CT pulmonary obstruction index, and parenchymal abnormalities at CT were not associated with the development of PE.CONCLUSIONS:PEs are present in about one fifth of a Chinese population of patients with pulmonary embolism, which are usually small, unilateral, and unsuitable for diagnostic thoracentesis.