Dynamic flyer in barrel imaging via high intensity short-pulse laser.

The thin flyer is a small-scale flying object, which is well known as the core functional element of the initiator. Understanding how flyers perform has been a long-standing issue in detonator science. However, it remains a significant challenge to explore how the flyer is formed and functions in the barrel of the initiator via tabletop devices. In this study, we present dynamic and unprecedented images of flyer in barrel via high intensity short-pulse laser. Advanced radiography, coupled with a high-intensity picosecond laser X-ray source, has enabled the provision of state-of-the-art radiographs in a single-shot experiment for observing micron-scale flyer formation in a hollow cylinder in nanoseconds. The flyer was clearly visible in the barrel and was accelerated and restricted differently from that without the barrel. This first implementation of a tabletop X-ray source provided a new approach for capturing dynamic photographs of small-scale flying objects, which were previously reported to be accessible only via an X-ray phase-contrast imaging system at the advanced photon source. These efforts have led to a significant improvement of radiographic capability and a greater understanding of the mechanisms of "burst" of exploding foil initiators for this application.

Mesenchymal stromal cells-derived small extracellular vesicles modulate DC function to suppress Th2 responses via IL-10 in patients with allergic rhinitis.

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC-derived small extracellular vesicles (MSC-sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC-sEV on DCs in allergic diseases remain unclear. MSC-sEV were prepared from the induced pluripotent stem cells (iPSC)-MSCs by anion-exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte-derived DCs were generated and cultured in the presence of MSC-sEV to differentiate the so-called sEV-immature DCs (sEV-iDCs) and sEV-mature DCs (sEV-mDCs), respectively. The phenotypes and the phagocytic ability of sEV-iDCs were analyzed by flow cytometry. sEV-mDCs were co-cultured with isolated CD4+ T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC-sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA-DR, but had no effects on mDCs with these markers. However, MSC-sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti-IL-10 monoclonal antibody or IL-10Rα blocking antibody, we identified that sEV-mDCs suppressed the Th2 immune response by reducing the production of IL-4, IL-9, and IL-13 via IL-10. Furthermore, sEV-mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC-sEV inhibited the Th2 responses, providing novel evidence of the potential cell-free therapy acting on DCs in allergic airway diseases.

Mesenchymal stem cells regulate type 2 innate lymphoid cells via regulatory T cells through ICOS-ICOSL interaction.

Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH 2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin- ) cells. PBMCs and Lin- cells were cocultured with induced pluripotent stem cell-derived MSCs (iPSC-MSCs) under the stimulation of epithelial cytokines IL-25 and IL-33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS-ICOSL pathway. iPSC-MSCs successfully decreased the high levels of IL-13, IL-9, and IL-5 in PBMCs in response to IL-25, IL-33, and the high percentages of IL-13+ ILC2s and IL-9+ ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC-MSCs. However, iPSC-MSCs were found directly to enhance ILC2 levels and functions via ICOS-ICOSL interaction in Lin- cells and pure ILC2s. iPSC-MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS-ICOSL interaction. The MSC-induced Treg cells then suppressed ILC2s by secreting IL-10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS-ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders.

A Prospective Study Comparing Cancer Detection Rates of Transperineal Prostate Biopsies Performed by Junior Urologists versus a Senior Consultant in a Real-World Setting.

INTRODUCTION: Prostate biopsy (PB) is a typical daily practice method for the diagnosis of prostate cancer (PCa). This study aimed to compare the PCa detection rates and peri- and postoperative complications of PB among 3 residents and a consultant. PATIENTS AND METHODS: A total of 343 patients who underwent PB between August 2018 and July 2019 were involved in this study. Residents were systematically trained for 2 weeks by a consultant for performing systematic biopsy (SB) and targeted biopsy (TB). And then, 3 residents and the consultant performed PB independently every quarter due to routine rotation in daily practice. The peri- and postoperative data were collected from a prospectively maintained database (www.pc-follow.cn). The primary outcome and secondary outcome were to compare the PCa detection rates and complications between the residents and consultant, respectively. RESULTS: There was no significant difference between the residents and consultant in terms of overall PCa detection rates of SB and TB or further stratified by prostate-specific antigen value and prostate imaging reporting and data system (PI-RADS) scores. We found the consultant had more TB cores (175 cores vs. 86-114 cores, p = 0.043) and shorter procedural time (mean 16 min vs. 19.7-20.1 min, p < 0.001) versus the residents. The complication rate for the consultant was 6.7% and 5%-8.2% for the residents, respectively (p = 0.875). CONCLUSIONS: The residents could get similar PCa detection and complication rates compared with that of the consultant after a 2-week training. However, the residents still need more cases to shorten the time of the biopsy procedure.

[Remitting Seronegative Symmetrical Synovitis with Pitting Edema associated with Lung Malignancy:Case Report and Literature Review].

Remitting seronegative symmetrical synovitis with pitting edema(RS3PE),the inflammatory arthritis attacking mainly elderly males,is characterized by symmetrical synovitis with pitting edema of the dorsum of hands and feet and the absence of rheumatoid factor.RS3PE commonly accompanies malignant tumor,infections and other diseases.Here we report a case of RS3PE associated with lung malignancy and review other six cases to summarize the clinical features,treatment and prognosis.

A Novel Prediction Tool Based on Multiparametric Magnetic Resonance Imaging to Determine the Biopsy Strategy for Clinically Significant Prostate Cancer in Patients with PSA Levels Less than 50 ng/ml.

PURPOSE: To develop and internally validate nomograms to help choose the optimal biopsy strategy among no biopsy, targeted biopsy (TB) only, or TB plus systematic biopsy (SB). PATIENTS AND METHODS: This retrospective study included a total of 385 patients who underwent magnetic resonance imaging (MRI)-guided TB and/or SB at our institute after undergoing multiparametric MRI (mpMRI) between 2015 and 2018. We developed models to predict clinically significant prostate cancer (csPCa) based on suspicious lesions from a TB result and based on the whole prostate gland from the results of TB plus SB or SB only. Nomograms were generated using logistic regression and evaluated using receiver-operating characteristic (ROC) curve analysis, calibration curves and decision analysis. The results were validated using ROC curve and calibration on 177 patients from 2018 to 2019 at the same institute. RESULTS: In the multivariate analyses, prostate-specific antigen level, prostate volume, and the Prostate Imaging Reporting and Data System score were predictors of csPCa in both nomograms. Age was also included in the model for suspicious lesions, while obesity was included in the model for the whole gland. The area under the curve (AUC) in the ROC analyses of the prediction models was 0.755 for suspicious lesions and 0.887 for the whole gland. Both models performed well in the calibration and decision analyses. In the validation cohort, the ROC curve described the AUCs of 0.723 and 0.917 for the nomogram of suspicious lesions and nomogram of the whole gland, respectively. Also, the calibration curve detected low error rates for both models. CONCLUSION: Nomograms with excellent discriminative ability were developed and validated. These nomograms can be used to select the optimal biopsy strategy for individual patients in the future.

Electromagnetic navigational bronchoscopy-directed dye marking for locating pulmonary nodules.

BACKGROUND: Small peripheral pulmonary nodules, which are usually deep-seated with no visual markers on the pleural surface, are often difficult to locate during surgery. At present, CT-guided percutaneous techniques are used to locate pulmonary nodules, but this method has many limitations. Thus, we aimed to evaluate the accuracy and feasibility of electromagnetic navigational bronchoscopy (ENB) with pleural dye to locate small peripheral pulmonary nodules before video-associated thoracic surgery (VATS). METHODS: The ENB localisation procedure was performed under general anaesthesia in an operating room. Once the locatable guide wire, covered with a sheath, reached the ideal location, it was withdrawn and 0.2-1.0 mL of methylene blue/indocyanine green was injected through the guide sheath. Thereafter, 20-60 mL of air was instilled to disperse the dye to the pleura near the nodules. VATS was then performed immediately. RESULTS: Study subjects included 25 patients with 28 nodules. The mean largest diameter of the pulmonary nodules was 11.8 mm (range, 6.0-24.0 mm), and the mean distance from the nearest pleural surface was 13.4 mm (range, 2.5-34.9 mm). After the ENB-guided localisation procedure was completed, the dye was visualised in 23 nodules (82.1%) using VATS. The average duration of the ENB-guided pleural dye marking procedure was 12.6 min (range, 4-30 min). The resection margins were negative in all malignant nodules. Complications unrelated to the ENB-guided localisation procedure occurred in two patients, including one case of haemorrhage and one case of slow intraoperative heart rate. CONCLUSION: ENB can be used to safely and accurately locate small peripheral pulmonary nodules and guide surgical resection. TRIAL REGISTRATION NUMBER: ChiCTR1900021963.

TAT-modified self-assembled cationic peptide nanoparticles as an efficient antibacterial agent.

The increasing emergence of drug resistant pathogenic bacteria poses a great challenge to clinical therapy and a threat to public health. Cationic peptides have received great attention for their unique antibacterial mechanism and ability to combat drug-resistant bacteria. In this study, we designed a TAT-modified cationic peptide PA-28 which self-assembled into nanoparticles of about 150 nm. These nanoparticles showed strong antimicrobial activities against both gram-positive and gram-negative bacteria, including drug-resistant bacteria. They were more potent than the unassembled counterpart peptide nonalysine (K9). Their antibacterial mechanism of directly destructing bacterial wall/membrane reduces the possibility of developing bacterial resistance. In vivo anti-infective experiments showed that these nanoparticles were able to penetrate the blood-brain barrier to inhibit bacterial growth in infected brains of rats. In addition, these nanoparticles induced low hemolysis below the minimum inhibitory concentration. Therefore, the peptide designed in this study is a promising and efficient antibacterial agent against bacterial infections.

Endoscopic retrograde appendicitis techniques for the treatment of patients with acute appendicitis.

OBJECTIVE: The purpose of this study was to demonstrate the feasibility of endoscopic retrograde appendicitis therapy (ERAT) in treating patients with acute appendicitis. MATERIALS AND METHODS: Between January 2014 and December 2014, 22 patients with acute appendicitis underwent ERAT. Patient demographics, colonoscopy findings, endoscopic retrograde appendiceal radiography (ERAR) findings, and treatment outcomes of the ERAT and adverse events associated with ERAT were analyzed. RESULTS: In this study, 22 patients with acute appendicitis underwent ERAT. The median age of the patients was 39.5 years. Colonoscopy findings included mucosal hyperemia and swelling of the appendiceal orifice and/or its surrounding mucosa (86.4 %, 19/22) and pus at the appendiceal orifice (40.9 %, 9/22). ERAR findings included irregular contour (76.2 %, 16/21), appendiceal lumen dilation (28.6 %, 6/21), appendiceal lumen stenosis (42.9 %, 9/21), and filling defect of the appendiceal lumen (23.8 %, 5/21). Deep intubation was successfully performed in 21 of the 22 patients (95.5 %). Sixteen patients underwent endoscopic appendiceal stent placement after endoscopic appendiceal irrigation (EAI) due to lumen stenosis of the appendiceal, excessive pus, or appendiceal fecalith, and the remaining 6 patients only underwent EAI. Among the 22 patients who underwent ERAT, their abdominal pain was noticeably relieved following the procedure. The main adverse events associated with ERAT were spontaneous discharge of the stent, recurrent abdominal pain, and recurrent appendicitis. During the follow-up (median 33 months), 2 patients underwent laparoscopic appendectomy. CONCLUSIONS: ERAT provide a new alternative therapeutic method for patients with acute appendicitis, particularly for certain patients who are unwilling to undergo an appendectomy.

[Study on Chemical Constituents from Hypocotyls of Mangrove Bruguiera gymnorrhiza].

OBJECTIVE: To study the chemical constituents from the hypocotyls of mangrove Bruguiera gymnorrhiza. METHODS: The chemical constituents were isolated and purified by recrystallization, silica gel column chromatography and semi-preparative HPLC. Their structures were identified by spectroscopic analysis and comparison with literatures. RESULTS: Seven compounds were isolated and their structures were identified as 3-ß-(Z)-coumaroyllupeol (1), dioslupecin (2), cholesterol (3), menisdaurillide (4), aquilegiolide (5) vomifoliol (6) and roseoside II (7). CONCLUSION: Compounds 1,2 and 4 - 7 are isolated from this plant for the first time.

[Macronutrients and energy in milk from mothers of premature infants].

OBJECTIVE: To study the dynamic changes in macronutrients and energy in human milk from mothers of premature infants. METHODS: A total of 339 human milk samples were collected from 170 women who delivered preterm or full-term infants in the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital between November 2012 and January 2014. Macronutrients (proteins, fats and carbohydrates and energy were measured using a MIRIS human milk analyzer and compared between groups. RESULTS: In milk samples from premature infants' mothers, the protein levels were the highest in colostrum (2.22±0.49 g/dL), less in transitional milk (1.83±0.39 g/dL), and the least in mature milk (1.40±0.28 g/dL) (P<0.01), and the levels of fats (2.4±1.3 g/dL vs 3.1±1.1 g/dL; P<0.01), carbohydrates (6.4±0.9 g/dL vs 6.6±0.4 g/dL; P<0.05) and energy (55±9 kcal/dL vs 62±8 kcal/dL; P<0.01) were significantly lower in colostrum than in transitional milk. The protein levels in colostrum from premature infants' mothers were significantly higher than those in colostrum from term infants' mothers (2.22±0.49 g/dL vs 2.07±0.34 g/dL; P<0.05). The colostrum from mothers of premature infants with a gestational age of ≤30 weeks had significantly higher protein levels than those from mothers of premature infants with gestational ages of 30(+1)-33(+6) weeks and ≥34 weeks (2.48±0.68 g/dL vs 2.11±0.25 g/dL and 2.22±0.39 g/dL respectively, P<0.05); the energy levels in colostrum from mothers of premature infants with a gestational age of ≤30 weeks group (51±6 kcal/dL) were significantly lower than those in colostrum from mothers of premature infants with a gestational age of 30(+1)-33(+6) weeks (58±8 kcal/d; P<0.05). The carbohydrate levels in transitional milk from mothers of premature infants with a gestational age of ≤30 weeks were significantly higher than those in transitional milk from mothers of premature infants with gestational ages of 30(+1)-33(+6) weeks and ≥34 weeks (P<0.05). The protein levels in mature milk from mothers of premature infants with a gestational age of 30(+1)-33(+6) weeks were significantly higher than those in mature milk from mothers of premature infants with gestational ages of ≤30 weeks and ≥34 weeks (P<0.05). CONCLUSIONS: The levels of macronutrients and energy in milk from mothers of premature infants vary significantly between colostrum, transitional milk, and mature milk. Protein levels are significantly higher in colostrum from premature infants' mothers than in colostrum from term infants' mothers, but the significant difference is not seen for mature milk. Macronutrient and energy levels show significant differences between milk samples from mothers of premature infants with different gestational ages, so as to meet different needs of premature infants.

A Good Prognosis of Patients with Acute Pancreatitis Combined with Pulmonary Embolism: Early Identification and Intervention.

BACKGROUND: Pulmonary embolism (PE) is a relatively rare vascular complication of acute pancreatitis (AP), and its mortality rate is high. To our knowledge, relevant literature reports still need to be summarized. In this study, we analyzed the clinical characteristics, treatment, and prognosis of five patients with AP complicated by PE and summarized and reviewed the relevant literature. METHODS: Clinical data of patients with AP complicated by PE treated in Taizhou Hospital of Zhejiang Province between January 2017 and September 2022 were retrospectively collected. Combined with the relevant literature, the clinical characteristics, treatment, and prognoses of patients with AP combined with PE were analyzed and summarized. RESULTS: Five patients were eventually enrolled in this study. Among the five patients with AP complicated by PE, all (100%) had symptoms of malaise, primarily chest tightness, shortness of breath, and dyspnea. All patients (100%) had varied degrees of elevated D-dimer levels and a significant decrease in the pressure of partial oxygen (PO2) and pressure of arterial oxygen to fractional inspired oxygen concentration ratio (PaO2/FiO2). Computed tomographic angiography (CTA) or pulmonary ventilation/perfusion imaging revealed a pulmonary artery filling defect in these patients. One patient (20%) had left calf muscular venous thrombosis before the occurrence of PE. Four patients (80%) were treated with lowmolecular- weight heparin (LMWH), and one patient (20%) was treated with rivaroxaban during hospitalization; all continued oral anticoagulant therapy after discharge. All patients (100%) were cured and discharged. No patients showed recurrence of AP or PE. CONCLUSION: PE is a rare but life-threatening complication of AP. However, once diagnosed, early treatment with anticoagulation or radiological interventional procedures is effective, and the prognosis is good. Core Tips: Pulmonary embolism (PE) is a rare but life-threatening complication of acute pancreatitis (AP). Its early diagnosis and timely anticoagulation or radiological intervention can reduce mortality. However, only nine cases have been reported in the English literature thus far, and they are all case reports. Our study is the first systematic analysis of patients with AP combined with PE with a review of the relevant literature. Our patients and those reported in the literature were discharged with good prognoses under treatment such as anticoagulation and vascular intervention. These cases remind clinicians that, in patients with AP, especially those with risk factors for venous thrombosis, it is necessary to monitor the D-dimer level dynamically. Clinicians should pay attention to AP patients' symptoms and related examinations to reduce the chance of a missed diagnosis or misdiagnosis of PE.

Accumulation of antitumor polyketides by fermentation of Rubus delavayi Franch. with Clonostachys rogersoniana.

The aim of this work is to explore the effects of herbal medicine on secondary metabolites of microorganisms during fermentation. Clonostachys rogersoniana was found to metabolize only small amounts of polyketide glycosides rogerson B and C on fresh potatoes, but after replacing the medium to the medicinal plant Rubus delavayi Franch., the type and content of the metabolized polyketones showed significant changes. The sugars and glycosides in R. delavayi are probably responsible for the changes in secondary metabolites. Six polyketide glycosides including a new metabolite, rogerson F, and two potential antitumor compounds, TMC-151C and TMC-151D, were isolated from the extract of R. delavayi fermented by C. rogersoniana. In addition, 13C labeling experiments were used to trace the biosynthesis process of these compounds. TMC-151C and TMC-151D showed significant cytotoxic activity against PANC-1, K562 and HCT116 cancer cells but had no obvious cytotoxic activity against BEAS-2B human normal lung epithelial cells. The yields of TMC-151C and TMC-151D reached 14.37 ± 1.52 g/kg and 1.98 ± 0.43 g/kg, respectively, after fermentation at 28 °C for 30 days. This is the first study to confirm that herbal medicine can induce microbes to metabolize active compounds. And the technology of fermenting medicinal materials can bring more economic value to medicinal plants.

Small extracellular vesicles derived from human mesenchymal stem cells prevent Th17-dominant neutrophilic airway inflammation via immunoregulation on Th17 cells.

Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.

Safety and efficacy of endoscopic excavation for gastric subepithelial tumors originating from the muscularis propria layer: results from a large study in China.

BACKGROUND AND AIM: In this retrospective study, we investigated the safety and efficacy of endoscopic excavation of gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer. MATERIALS AND METHODS: Between November 2007 and June 2012, 212 patients with gastric SETs originating from the MP layer were treated via endoscopic excavation. The key procedures were: (1) injecting a mixture solution (100 mL saline+2 mL indigo carmine+1 mL epinephrine) into the submucosa around the tumor; (2) making a cross-incision of the mucosa and then excavating the tumor by the technique of endoscopic excavation. After the tumor was completely excavated from the MP layer, it was removed using a snare; (3) closing the artificial ulcer with clips. RESULTS: The mean diameter of the 212 tumors was 16.5 mm. Complete resection by endoscopic excavation was achieved in 204 cases (96.2%). The rate of complete resection was significantly higher for tumors <2 cm (98.0%) than for tumors >2 cm (91.9%) (P=0.035). Perforation occurred in 32 cases (15.1%), and massive bleeding occurred in 9 cases (4.2%) during the procedure. The rate of perforation was significantly higher for the fundus and the body than for antrum (21.5%, 11.5%, 0%, respectively; P=0.036), and also differed significantly in relation to histologic diagnosis (23.7% for gastrointestinal stromal tumors vs. 7.8% for leiomyoma; P=0.001). Histologic diagnosis showed that the density of gastrointestinal stromal tumors located in the fundus and the body of the stomach was significantly higher than in the antrum (44.1%, 51.9%, 13.3%, respectively; P=0.036). CONCLUSIONS: Endoscopic excavation is a safe and efficient method for resecting small (>3.5 cm) gastric SETs originating from the MP layer.

3-Acyl-5-hydroxybenzofuran derivatives as potential anti-estrogen breast cancer agents: a combined experimental and theoretical investigation.

We first report the application of 3-acyl-5-hydroxybenzofurans as a scaffold to develop potential drugs for breast cancer. Seven novel derivative compounds were synthesized by using a microwave-assisted synthesis method. Those compounds exhibited different antiproliferation against human breast cancer MCF-7 cells, with the best activity of IC50=43.08µM for compound 1. A Quantum Mechanics Polarized Ligand Docking (QPLD) study was carried out to investigate the binding interactions between these compounds and estrogen receptor alpha (ERα). The simulation results showed that the trend of receptor-ligand binding interactions was same as that of their antiproliferative activities. A detailed analysis indicated that compound 1 possesses the highest Van der Waals and hydrogen bond interactions compared to the other six compounds and better inhibitors are achievable by enhancing the hydrogen bond interactions. Based on these results, we addressed that 3-acyl-5-hydroxybenzofuran is an attractive scaffold for designing drugs against breast cancer.

[Non-real-time endobronchial bronchoscopy ultrasound assisted transbronchial lung biopsy in diagnosing peripheral pulmonary lesions].

OBJECTIVE: To evaluate the role of non-real-time endobronchial bronchoscopy ultrasound(EBUS) assisted transbronchial lung biopsy (TBLB) in diagnosing peripheral pulmonary lesions (PPL). METHODS: One hundred and five patients [68 males and 37 females, mean age (59 ± 12) years, ranged from 39 - 81 years] with PPL confirmed by computered tomography (CT) were recruited in this study between June 1st 2011 and March 1st 2012. All cases received bronchoscopy examinations and presented with roughly normal results. Fifty-four cases received EBUS examinations. For peripheral lesions with accessible EBUS images, blind biopsy was performed with biopsy forceps through pathways of the ultrasonic probe after the retreat of the probe. In those cases without accessible EBUS images, blind biopsy was performed based on the localization by image data. The other 51 cases without EBUS testing underwent blind biopsy on the localization by image data. Positive rates of pathological diagnosis of the 2 groups were compared. Analysis was by χ(2)-test. RESULTS: In 54 patients who received EBUS examinations, 76% (41/54) of PPLs were detected performed by EBUS. The positive rate of the EBUS assisted TBLB group was 67% (36/54), compared with 45% (23/51) in the general TBLB group. There was a better diagnostic rate (P < 0.05) in the EBUS assisted TBLB group than the general TBLB group. Thirteen patients without accessible EBUS images obtained negative pathological results. The diagnosis rate of EBUS assisted TBLB on lesions with ≤ 30 mm minimum diameter was 44% (8/18), lower than 78% (28/36) on lesions with > 30 mm minimum diameter (P < 0.05). In terms of diagnosis rate on lesions with ≤ 30 mm minimum diameter, EBUS assisted TBLB was 44% (8/18), higher than 12% (2/17) of TBLB alone (P < 0.05). As for lesions with > 30 mm minimum diameter, diagnosis rate of EBUS assisted TBLB was 52% (28/54) and TBLB alone was 41% (21/51), representing insignificant difference (P > 0.05). In the EBUS assisted TBLB group, we performed 269 blind biopsies, with an average of 4.8 times per case, whereas the general TBLB group required 398 times, with an average of 7.8 times per case. EBUS assisted TBLB decreased the operation times of blind biopsy (P < 0.05) to acquire adequate and appropriate specimen. Complications of biopsy occurred in this study included slight haemoptysis (61/105, 58.1%), chest pain (25/105, 23.8%) and pneumothorax (2/105, 1.9%). Patients with these complications recovered spontaneously without special managements. CONCLUSIONS: Non-real-time EBUS assisted TBLB could improve diagnostic positive rate without increasing operational risk. In most cases, the blind biopsy did not succeed if EBUS failed to detect the lesions. The success rate of non-real-time EBUS assisted TBLB was related to the minimum diameter of PPL. In terms of diagnosis rate on lesions with ≤ 30 mm minimum diameter, EBUS assisted TBLB was higher than TBLB alone. As for lesions with >30mm minimum diameter, there was no significant difference in the diagnosis rate between these 2 groups. EBUS assisted TBLB decreased the times of blind biopsy process (P < 0.05) to obtain adequate and appropriate specimen.

Dendritic cells mediated by small extracellular vesicles derived from MSCs attenuated the ILC2 activity via PGE2 in patients with allergic rhinitis.

BACKGROUND: Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs. METHODS: Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems. RESULTS: sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs. CONCLUSIONS: We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.