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BackgroundThe early radiologic signs of progression in bronchiectasis remain unclear.ObjectivesTo compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for evaluating radiological progression of bronchiectasisviastratifyng the presence (TW+) or absence (TW-) of thickened-walled bronchioles surrounding dilated bronchi among patients with bronchiectasis based on CT, and determine the risk factors.MethodsIn this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway caliber metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway caliber metrics between group TW+ and TW-. We ascertained radiological progression at 5 yearsviaCT and EB-OCT.ResultsWe recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics - mean luminal diameter (p=0.017), inner airway area (p=0.005), and airway wall area (p=0.009) of 7th-9th generation bronchioles were significantly greater in group TW+ than in group TW-. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding non-dilated bronchi on CT in group TW-. At 5 years, 53.1% of patients in group TW+ progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in group TW- (pConclusionThickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.

Background: Manual measurement of endobronchial optical coherence tomography (EB-OCT) images means a heavy workload in the clinical practice, which can also introduce bias if the subjective opinions of doctors are involved. Objective: We aim to develop a convolutional neural network (CNN)-based EB-OCT image analysis algorithm to automatically identify and measure EB-OCT parameters of airway morphology. Methods: The ResUNet, MultiResUNet, and Siamese network were used for analyzing airway inner area (Ai), airway wall area (Aw), airway wall area percentage (Aw%), and airway bifurcate segmentation obtained from EB-OCT imaging, respectively. The accuracy of the automatic segmentations was verified by comparing with manual measurements. Results: Thirty-three patients who were diagnosed with asthma (n = 13), chronic obstructive pulmonary disease (COPD, n = 13), and normal airway (n = 7) were enrolled. EB-OCT was performed in RB9 segment (lateral basal segment of the right lower lobe), and a total of 17,820 OCT images were collected for CNN training, validation, and testing. After training, the Ai, Aw, and airway bifurcate were readily identified in both normal airway and airways of asthma and COPD. The ResUNet and the MultiResUNet resulted in a mean dice similarity coefficient of 0.97 and 0.95 for Ai and Aw segmentation. The accuracy Siamese network in identifying airway bifurcate was 96.6%. Bland-Altman analysis indicated there was a negligible bias between manual and CNN measurements for Ai (bias = −0.02 to 0.01, 95% CI = −0.12 to 0.14) and Aw% (bias = −0.06 to 0.12, 95% CI = −1.98 to 2.14). Conclusion: EB-OCT imaging in conjunction with ResUNet, MultiResUNet, and Siamese network could automatically measure normal and diseased airway structure with an accurate performance.

SUMMARY A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

Business Process Management (BPM) is an important discipline for organizations to manage their business processes. Research shows that higher BPM-maturity leads to better process performance. However, contextual factors such as culture seem to influence this relationship. The purpose of this paper is to investigate the role of national culture on the relationship between BPM-maturity and process performance. A multiple linear regression analysis is performed based on data from six different countries within Europe. Although the results show a significant relationship between BPM-maturity and process performance, no significant moderation effect of national culture has been found. The cultural dimension long term orientation shows a weak negative correlation with both BPM-maturity and process performance. Through a post-hoc moderation analysis on each dimension of BPM-maturity, we further find that long term orientation negatively moderates the relationship between process improvement and process performance. Three other moderation effects are also discovered. The results of this study contribute to insights into the role of culture in the field of BPM.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/β-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

A graphene-supported highly dispersed cobalt catalyst with abundant Co–Nx active sites was synthesized to boost 1O2 production from H2O2 activation, exhibiting excellent degradation efficiency towards the model organic pollutant methylene blue.

Background The effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear. Methods We recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs’ lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT. Results Patients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)–positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment. Conclusions BT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.

Additional file 1. Table S1: Primers and sequence information for PCR used to characterize respiratory viruses. Table S2: Primers, probes and sequence information for PCR used to characterize respiratory bacteria. Fig. S1: Valid tags and OTUs obtained from samples. OUT, operational taxonomic unit. Fig. S2: Top 30 genera (A) and species (B) of bacteria in relative abundance among all the samples. Table S3: Bacteria of statistically significant difference between IFVP group and IFVN group at the genus level. Table S4: Bacteria of statistically significant difference between IFVP group and IFVN group at the species level.

BACKGROUND: Airway stenting is frequently used in the palliative treatment of patients with advanced tumor-induced airway stenosis and fistulas. However, there is paucity of studies regarding the use of airway stents in restoring patency. The aim of the study was to assess the efficacy and safety of hybrid silicon Y stents and covered self-expanding metal stents (SEMS) and in reestablishing patency in airway stenoses and fistulas. METHODS: This retrospective study included 31 patients between January 2016 to December 2019 with inoperable complex malignant airway stenoses and fistulas, managed with Silicone Y stents, and covered SEMS. The clinical details, clinical outcomes and complications up to 6 months were extracted from medical records. The improvement of performance was assessed based on modified British Medical Research Council (mMRC) dyspnea scores (t=6.892, P

BACKGROUND: Transbronchial cryobiopsy (TBCB) is an option to surgical biopsy for the diagnosis in interstitial lung diseases. Several impact factors have received wide attention, including the freezing time, cryoprobe size, and contact pressure. However, the effect of the applied gas pressure on the specimen size has not been well elucidated. The purpose of this study is to investigate the effect of the applied gas pressure on the TBCB specimen size. METHODS: Cryoprobes with a diameter of 1.9 mm were used to perform TBCB on 4 beagle canines under general anesthesia. TBCB was performed with a total of 16 time-pressure combinations that were randomly combined with 4 freezing times (3, 4, 5, and 6 s) and 4 gas pressures (40, 50, 55, and 60 bar). For each combination, 8 biopsies were performed. The size and quality of specimens, as well as complications, were evaluated. RESULTS: A total of 128 TBCB specimens were obtained. With the same freezing time, the specimen sizes obtained by different applied gas pressures were significantly different (P

Singlet oxygen (

Background Understanding asthmatic airway structural changes and the bronchodilator responses may help unravel targets for intervention. However, structural abnormalities of asthmatic airways with different disease severity and the major anatomical site of bronchodilator responses have not been well elucidated. We aim to evaluate the airway remodeling characteristics and the bronchodilator responses in medium-sized and small airways of asthma. Methods We recruited 104 asthmatic patients and 31 non-smoking control subjects to compare the airway inner area (Ai) and airway wall area percentage (Aw%) with endobronchial optical coherence tomography. We also enrolled 32 patients with moderate-to-severe asthma to dynamically assess the airway morphological changes after salbutamol inhalation. Results More prominent airway structural abnormalities correlated with greater asthma severity, evidenced by the decreased Ai and greater Aw% in medium-sized and small airways. Patients with mild asthma yielded comparable Ai but greater Aw% than control subjects. Salbutamol inhalation led to a rapid dilatation of both medium-sized and small airways, the lung function improvement correlated significantly with the increase in Ai of the medium-sized, but not small, airways at 15 min. Conclusion Luminal narrowing and airway wall thickening of the medium-sized and small airways are present in mild asthma and reflect asthma severity, lending support to the use of anti-imflammatory intervention in mild asthma. The medium-sized airways are the crucial site of the bronchodilator responses, providing the scientific rationale for future development of more effective delivery of inhaled medications for asthma.

Background: The predictors and airway morphological changes during the development of postintubation tracheal stenosis (PITS) have not been well elucidated. Objectives: To elucidate the validation of endobronchial optical coherence tomography (EB-OCT) in assessing the airway morphological changes in PITS. Methods: We performed oral endotracheal intubation in 12 beagles to establish the PITS model. EB-OCT was performed respectively before modeling and on the 1st, 7th, and 12th day after extubation in 9 canines, and was conducted consecutively in 3 canines during the development of PITS. Histological findings and the thickness and gray-scale value of the tracheal wall assessed by EB-OCT measurements were analyzed and compared. Results: The tracheal wall edema, granulation tissue proliferation, cartilage destruction in PITS, and airway wall thickening detected by EB-OCT were in concordance with the histopathological measurements. The consecutive EB-OCT observation of the airway structure demonstrated the tracheal wall thickness significantly increased from 344.41 ± 44.19 μm before modeling to 796.67 ± 49.75 μm on the 9th day after modeling (p < 0.05). The airway wall gray-scale values assessed by EB-OCT decreased from 111.19 ± 14.71 before modeling to 74.96 ± 4.08 on the 9th day after modeling (p < 0.05). The gray-scale value was negatively correlated with the airway wall thickness (r = –0.945, p = 0.001). Conclusion: The EB-OCT imaging, in concordance with the histopathological finding, was validated for assessing the airway morphological changes during the development of PITS. The EB-OCT evaluation of cartilage damage and gray-scale value measurement might help predict the development and prognosis of PITS.

Background: A few studies have reported the medium-sized and small airway morphological abnormalities of bronchiolitis. Whether spirometry or impulse oscillometry (IOS) is correlated with airway remodeling of bronchiolitis remains unclear. Objectives: Aiming to demonstrate the airway morphological abnormalities of bronchiolitis obliterans (BO) and diffuse panbronchiolitis (DPB) assessed by endobronchial optical coherence tomography (EB-OCT), and elucidate whether spirometric and IOS parameters have correlation with the airway remodeling of bronchiolitis. Methods: We recruited 18 patients with bronchiolitis (BO, n = 9; DPB, n = 9) and 17 control subjects. Assessments of clinical features, St. George’s respiratory questionnaire (SGRQ), chest computed tomography (CT), spirometry, IOS, and EB-OCT were performed in all enrolled subjects. The correlation between EB-OCT and lung function parameters was studied and analyzed. Results: The magnitude of abnormalities of spirometric and IOS parameters was significantly greater in patients with bronchiolitis than that in control subjects ( p 1), forced vital capacity (FVC), FEV1/FVC, maximal mid-expiratory flow (MMEF)% pred and higher resonant frequency (Fres), and area of reactance (AX) than those with DPB ( p 5–R20) correlated negatively with medium-sized and small airway inner area, and correlated positively with airway wall area ( p Conclusion: Bronchiolitis, BO and DPB, manifested a heterogeneous distribution of airway calibers with significant intra- and inter-individual variability. IOS parameters, rather than spirometry, correlated better with medium-sized and small airway remodeling in bronchiolitis assessed by EB-OCT measurement.

Background A feasible and economical bronchoscopic navigation method in guiding peripheral pulmonary nodule biopsy is lacking. Objective To investigate the utility of hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. Methods We developed a hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. Patients with peripheral pulmonary nodules were recruited and assigned to two groups in this retrospective study, subjects in VBN group received conventional bronchoscopy in conjunction with virtual bronchoscopic navigation (VBN) and radial probe endobronchial ultrasound (RP-EBUS) for biopsy (VBN group), while HBN group underwent ultrathin bronchoscopy and RP-EBUS under the guidance of hand-drawn bronchoscopic navigation (HBN). The demographic characteristics, procedural time, operating cost and diagnostic yield were compared between these two groups. Results Forty-eight patients with peripheral pulmonary nodule were enrolled in HBN group, while 42 in VBN group. There were no significant differences between VBN and HBN groups in terms of age, gender, lesion size, location and radiographic type. The time of planning pathway (1.32 vs. 9.79 min, P vs. 28.02 min, P = 0.002), as well as operating cost (758.31 ± 125.21 vs.1327.70 ± 116.25 USD, P vs. 61.90%, P = 0.25). Conclusions Hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation could serve as a feasible and economical method for guiding peripheral pulmonary nodule biopsy, providing a comparable diagnostic yield in comparison with virtual bronchoscopic navigation.

Background: The purpose of this study was to compare the clinical efficacy of robotic right colectomy (RRC) and laparoscopic right colectomy (LRC) in the treatment of right colon tumor. Methods: We systematically searched PubMed, Web of science, EMBASE ClinicalTrials.gov and Cochrane Central Register for studies (studies published between January 2011 and June 2020). The included studies compared the clinical efficacy of RRC and LRC in the treatment of right colon tumor, and analyzed the perioperative data. Results: Our meta-analysis included 10 studies involving 1180 patients who underwent 2 surgical procedures, RRC and LRC. This study showed that compared with LRC, there was no significant difference in first flatus passage (weighted mean difference [WMD]: −0.37, 95% CI: −1.09–0.36, P = .32), hospital length of stay (WMD: −0.23, 95% CI: −0.73–0.28, P = .32), reoperation (OR: 1.66, 95% CI: 0.67–4.10, P = .27), complication (OR: 0.83, 95% CI: 0.60–1.14, P = .25), mortality (OR: 0.45, 95% CI: 0.02–11.22, P = .63), wound infection (OR: 0.65, 95% CI: 0.34–1.25, P = .20), and anastomotic leak (OR: 0.73, 95% CI: 0.33–1.63, P = .44). This study showed that compared with LRC, the lymph nodes retrieved (WMD: 1.47, 95% CI: −0.00–2.94, P = .05) of RRC were similar, with slight advantages, and resulted in longer operative time (WMD: 65.20, 95% CI: 53.40–77.01, P

Insulators play a critical role in spatiotemporal gene regulation in animals. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here we explore the sequence requirements of CTCF-mediated transcriptional insulation using a sensitive insulator reporter in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF-binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on upstream flanking sequences at its binding sites. CTCF-binding sites at topologically associating domain boundaries are more likely to function as insulators than those outside topologically associating domain boundaries, independently of binding strength. We demonstrate that insulators form local chromatin domain boundaries and weaken enhancer-promoter contacts. Taken together, our results provide genetic, molecular and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome.

Background and aims: Post-tuberculosis bronchial stenosis (PTBS) is one of the most common complications of tracheobronchial tuberculosis. Silicone stent serves as a major treatment for maintaining airway patency. However, silicone stent placement remains a large challenge in patients with severe cicatricial PTBS. Our objective was to evaluate the efficacy and safety of covered, self-expanding, metallic stents (SEMSs) as a transition to silicone stent implantation for treating severe PTBS. Methods: We retrospectively reviewed the data of patients with severe PTBS who received airway stenting in the First Affiliated Hospital of Guangdong Medical University between September 2015 and May 2019. The types of the stent, intervention procedures, bronchoscopic findings, clinical outcomes and related complications were collected and analyzed. Results: Fifty-eight cases with severe PTBS were included in this study. Thirteen (22.4%) of the patients received bronchial silicone stent implantation immediately after dilations. For the remaining 45 (77.6%) patients, silicone stents could not be deployed after dilations and SEMSs implantation was implemented as a bridge to silicone stenting. The SEMSs were placed for an interval of 28.4 ± 11.1 days. All of the silicone stents were inserted successfully following the removal of SEMSs. No SEMS-related complication occurred. The subgroup analysis showed that patients who received transitional SEMSs had less luminal caliber but fewer transbronchial dilations before silicone stent implantation ( p Conclusion: Covered SEMS placement as a transition to silicone stenting could serve as a feasible procedure to reduce complications and improve the success rate of silicone stent implantation in patients with severe PTBS. The reviews of this paper are available via the supplemental material section.

Background The relationships between coagulation factors and non‐small cell lung cancer (NSCLC) prognosis have been intensively studied. However, no previous study has investigated the combined effects of preoperative platelet (PLT), fibrinogen (FIB), and D‐dimer (D‐D) levels on the prognosis of NSCLC. Methods A multicenter prospective study was conducted over seven hospitals. A total of 395 patients diagnosed with operable NSCLC for the first time were included and followed‐up until disease progression or the end of the study. Baseline demographic and clinicopathological information, and preoperative coagulation test results were collected for each patient. Univariate and multilevel survival analyses were conducted using Cox regression and shared frailty models. Results Multilevel analyses revealed that there was a marginally significant association between elevated PLT level (> 215 × 109/L) and unfavorable progression‐free survival (PFS) (hazard ratio 2.42, P = 0.05), whereas preoperative FIB and D‐D were not significant prognostic factors for PFS (P = 0.31 and 0.30, respectively). Compared to patients with one elevation of the three coagulation factors, patients with at least two elevations of the three factors had a significantly higher risk of cancer progression (hazard ratio 4.62, P = 0.02). Conclusion The number of elevated preoperative coagulation factors may have a significant effect on PFS and could be used to predict the prognosis of NSCLC patients after surgery. Future studies are warranted to further investigate the interactions between these three coagulation factors.

Background Extended or combined segmentectomies are usually adapted for intersegmental pulmonary nodules. This study explored precise combined subsegmentectomy (CSS) under the guidance of three‐dimensional computed tomography bronchography and angiography (3D‐CTBA). Methods The definition of a pulmonary intersegmental nodule was based on a minimum distance between the nodule and the involved intersegmental veins in the preoperative 3D‐CTBA being less than the size of the nodule. Centering on the involved intersegmental vein, two adjacent subsegments belonging to the different segments were combined as a resected unit. Results We retrospectively reviewed the records of 47 patients (mean age 53.6 ± 12.3, range: 26–81 years) who underwent CSS. Thirty‐nine (83.0%) nodules were involved in most intersegmental locations of the upper lobes; the remainder in the lower lobes. The mean nodule size was 0.86 ± 0.32 cm; the mean margin width was 2.20 ± 0.38 cm. Pathological stages included: Tis (8 cases), T1mi (16), IA1 (T1aN0M0, 13), and IA2 (T1bN0M0, 5). Pathological diagnoses included: invasive adenocarcinoma (18 cases), minimally invasive adenocarcinoma (16), adenocarcinoma in situ (8), atypical adenomatous hyperplasia (3), and benign (2). The average operative duration was 190.8 ± 54.9 minutes; operative hemorrhage was 42.7 ± 23.0 mL; 5.8 ± 2.8 lymph nodes dissected had not metastasized; the duration of postoperative chest tube drainage was 3.0 ± 1.8 days; and the postoperative hospital stay was 5.3 ± 2.4 days. Conclusions Under 3D navigation, thoracoscopic CSS is a safe technique for intersegmental nodules, sparing more pulmonary parenchyma and ensuring safe margins to achieve anatomical resection.

Background: The treatment of pulmonary malignancies remains a challenge. The efficacy and safety of bronchoscopic radiofrequency ablation (RFA) for the treatment of lung cancer are not well elucidated. Objective: This study aimed to evaluate the feasibility and safety of RFA guided by bronchoscopic transparenchymal nodule access (BTPNA) in vivo. Methods: In an attempt to determine the parameters of RFA, we first performed RFA in conjunction with automatic saline microperfusion in the lung in vitro with various ablation energy (10, 15, 20, 25, and 30 W) and ablation times (3, 5, 8, and 10 min). The correlation between ablated area and RFA parameter was recorded and analyzed. Further, we conducted a canine study with RFA by BTPNA in vivo, observing the ablation effect and morphological changes in the lung assessed by chest CT and histopathologic examination at various follow-up time points (1 day, n = 3; 30 days, n = 4; 90 days, n = 4). The related complications were also observed and recorded. Results: More ablation energy, but not ablation time, induced a greater range of ablation area in the lung. Ablation energy applied with 15 W for 3 min served as the appropriate setting for pulmonary lesions ≤1 cm. RFA guided by BTPNA was performed in 11 canines with 100% success rate. Inflammation, congestion, and coagulation necrosis were observed after ablation, which could be repaired within 7 days; subsequently, granulation and fibrotic scar tissue developed after 30 days. No procedure-related complication occurred during the operation or in the follow-up periods. Conclusion: The novel RFA system and catheter in conjunction with automatic saline microperfusion present a safe and feasible modality in pulmonary parenchyma. RFA guided by BTPNA appears to be well established with an acceptable tolerance; it might further provide therapeutic benefit in pulmonary malignancies.

Supplemental material, sj-pdf-4-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-5-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-2-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-1-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-3-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-1-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-3-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-2-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-4-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-5-tar-10.1177_17534666211019564 for Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis by Zi-Qing Zhou, Jia-Xin Feng, Yu Chen, Zhu-Quan Su, Chang-Hao Zhong, Xiao-Bo Chen, Chun-Li Tang, Jie-Rong Huang and Shi-Yue Li in Therapeutic Advances in Respiratory Disease

The convenient and effective detection of toxins is urgently demanded for food security and human health. Herein, based on the catalytic activity of mimetic peroxidase from the Cu

The fluctuation of water level in the Three Gorges Reservoir is up to 30 m, and the reservoir water fluctuation zone is the important channel of reservoir water flowing in and out of a landslide. The permeability characteristics and parameters of the reservoir water fluctuation zone of landslide bodies are of great significance for calculating the seepage of the reservoir landslide and evaluating the stability of the landslide. In this paper, 396 landslides in the Three Gorges Reservoir Area were studied, and 1188 test pits were sampled. In an analysis based on test data, the classification indicators of landslides can be divided into two types: provenance lithology and compositional structure. According to provenance lithology, the landslides can be divided into dolomite and limestone, marl, sandstone and mudstone inlaid rocks, siltstone, and argillaceous limestone. In addition, according to the compositional structure, landslide bodies can be divided into fine-grained soil, soil containing gravel stone, soil clip gravel stone, crushed rock soil, and fractured rock mass, where there are three types and five sub-categories. Based on this study, we found that the permeability of the landslide bodies has regional distribution characteristics, which is positively correlated with gravel content and provenance lithology strength and is mainly medium and better.

A multi-colorimetric immunosensor basing on the mimetic enzyme etching of gold nanobipyramids (Au NBPs) was established to detect ochratoxin A (OTA). Octahedral Cu2O nanoparticles were successfully synthesized through a selective surface stabilization strategy, which can exhibit a peroxidase-like ability to oxidize 3,3′,5,5′-tetramethylbenzidine (TMB). Au NBPs can be etched by the product, TMB2+, to form a significant longitudinal peak blue shift of local surface plasmon resonance. During the construction of the immunosensor, the microplate was coated with dopamine to immobilized OTA antigens, followed by the immunoreaction of OTA antibody and the Cu2O-labled secondary antibody. A linear relationship can be found between the local surface plasmon resonance (LSPR) peak changes with the logarithm of OTA concentration in a wide range from 1 ng/L to 5 μg/L, while the detection limit was 0.47 ng/L. Meanwhile, the approximate OTA concentration can be conveniently and intuitively observed by the vivid color changes. Benefiting from the high specificity, the proposed multi-colorimetric immunoassay detection of OTA in millet samples was achieved, indicating the available potential of the immunoassay for the determination of OTA in real samples.

Oxidase nanozymes have attracted particular attention in colorimetric immunoassay due to their high activity, stability, and biocompatibility. In this work, the well-dispersed Co(OH)2 nanocages were synthesized by a template-assisted strategy. The prepared Co(OH)2 nanocages exhibited an intrinsic oxidase-like activity, which can oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) without the addition of hydrogen peroxide (H2O2). Hence, a simple and sensitive colorimetric immunoassay was established to detect ochratoxin A (OTA). In this immunosensor, the microplates were modified with dopamine as the substrate to capture antigens. Then, the uniform Co(OH)2 nanocages were used as the vehicle to carry the secondary antibody for the recognition of immunoreaction. The sensing system can generate color responses with the OTA concentration in the range from 0.5 ng/L to 5 μg/L, and the detection limit was as low as 0.26 ng/L. Therefore, as a nano-artificial enzyme, Co(OH)2 nanocages may show promising potential in visual detection of the real samples.

Non-small cell lung cancer (NSCLC) is one of the most common aggressive malignancies. miRNAs have been identified as important biomarkers and regulators of NSCLC. However, the functional contributions of miR-1260b to NSCLC cell proliferation and apoptosis have not been studied. In this study, miR-1260b was upregulated in NSCLC plasma, tissues, and cell lines, and its high expression was correlated with tumor size and progression. Functionally, miR-1260b overexpression promoted cell proliferation and cell cycle, conversely inhibited cell apoptosis and senescence. Mechanically, miR-1260b negatively regulated SOCS6 by directly binding to its 3'-UTR. Furthermore, miR-1260b-mediated suppression of SOCS6 activated KIT signaling. Moreover, YY1 was an upstream regulator of miR-1260b. This study is the first to illustrate that miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate NSCLC cell proliferation and apoptosis, and is a potential biomarker and therapeutic target for NSCLC. In sum, our work provides new insights into the molecular mechanisms of NSCLC involved in cell proliferation and apoptosis.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a family of recently discovered lipids with important physiological functions in mammals and plants. However, low detection sensitivity in negative ionization mode mass spectrometry makes low-abundance FAHFA challenging to analyze. A 2-dimethylaminoethylamine (DMED) based chemical derivatization strategy was recently reported to improve the MS sensitivity of FAHFAs by labeling FAHFAs with a positively ionizable tertiary amine group. To facilitate reliable, high-throughput, and automatic annotation of these compounds, a DMED-FAHFA in silico library containing 4290 high-resolution tandem mass spectra covering 264 different FAHFA classes was developed. The construction of the library was based on the heuristic information from MS/MS fragmentation patterns of DMED-FAHFA authentic standards, and then, the patterns were applied to computer-generated DMED-FAHFAs. The developed DMED-FAHFA in silico library was demonstrated to be compatible with library search software NIST MS Search and the LC-MS/MS data processing tool MS-DIAL to guarantee high-throughput and automatic annotations. Applying the in silico library in Arabidopsis thaliana samples for profiling FAHFAs by high-resolution LC-MS/MS enabled the annotation of 19 DMED-FAHFAs from 16 families, including 3 novel compounds. Using the in silico library largely decreased the false-positive annotation rate in comparison to low-resolution LC-MS/MS. The developed library, MS/MS spectra, and development templates are freely available for commercial and noncommercial use at https://zenodo.org/record/3606905.

Supplemental material, sj-pdf-1-tam-10.1177_1758835920982845 for Lepidic component identifies a subgroup of lung adenocarcinoma with a distinctive prognosis: a multicenter propensity-matched analysis by Erjia Zhu, Chenyang Dai, Huikang Xie, Hang Su, Xuefei Hu, Ming Li, Junqiang Fan, Jinshi Liu, Quan Zhu, Lei Zhang, Honggang Ke and Chang Chen in Therapeutic Advances in Medical Oncology

Background: Asthma is characterized by chronic airway inflammation and remodeling. Understanding airway structural changes and the bronchodilator responses may help unravel targets for intervention. However, structural abnormalities of asthmatic airways with different disease severity and the major anatomical site of bronchodilator responses have not been well elucidated. Methods: We recruited 104 asthmatic patients (when clinically stable) and 31 non-smoking control subjects to compare the airway inner area (Ai) and airway wall area percentage (Aw%) with endobronchial optical coherence tomography. We also enrolled 32 patients with moderate-to-severe asthma to dynamically access the airway morphological changes after salbutamol inhalation. Findings: More prominent airway structural abnormalities correlated with greater asthma severity, evidenced by the decreased Ai and greater Aw% in medium-sized and small airways. Patients with mild asthma yielded comparable Ai but greater Aw% than control subjects. A longer disease duration correlated with lower Ai and greater Aw% from the 3rd to 6th generation of bronchi. Salbutamol inhalation led to a rapid dilatation of both medium-sized and small airways, the lung function improvement correlated significantly with the increase in Ai of the medium-sized, but not small, airways at 15 min. Interpretation: Luminal narrowing and airway wall thickening of the medium-sized and small airways are present in mild asthma and reflect asthma severity, lending support to the use of anti-imflammatory intervention in mild asthma. The medium-sized airways are the crucial site of the bronchodilator responses, providing the scientific rationale for future development of more effective delivery of inhaled medications for asthma. Funding Statement: National Natural Science Foundation of China (No.81770017), National Natural Science Foundation of China (No.81900032), Pearl River S&T Nova Program of Guangzhou No. 201710010097 and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017 Declaration of Interests: Prof. Li declared that he had received the National Natural Science Foundation of China (No.81770017). Dr Su declared that he had received the National Natural Science Foundation of China (No.81900032). Prof. Guan declared that he had received Pearl River S&T Nova Program of Guangzhou No. 201710010097, and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017. All other authors declared no potential conflict of interest. None of the funding sources had any role on the study Ethics Approval Statement: This study was approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (Medical Ethics [Year 2014] No. 51 and [Year 2019] No. K09). All subjects gave written informed consent.

Supplemental material, Supplemental_data.docxTAO for Procedure-specific prognostic impact of micropapillary subtype may guide resection strategy in small-sized lung adenocarcinomas: a multicenter study by Hang Su, Huikang Xie, Chenyang Dai, Shengnan Zhao, Dong Xie, Yunlang She, Yijiu Ren, Lei Zhang, Ziwen Fan, Donglai Chen, Feng Jiang, Jinshi Liu, Quan Zhu, Jie Yao, Honggang Ke, Lei Zhang, Chunyan Wu, Gening Jiang and Chang Chen in Therapeutic Advances in Medical Oncology

In order to meet the requirement of frequent start-stop of the units, it is significant to optimize the operation scheme of the unit. A novel optimized mathematical model of a steam turbine was proposed at a previous paper of this study’s authors. In this study the supported vector machine (SVM) stress model of a 320 MW steam turbine was established based on 13 groups of start-up schemes. According to the novel optimized mathematical model and SVM stress model of the turbine, Genetic algorithm-particle swarm optimization was employed to search for the best values of the steam temperature rise rate. The optimization schedule can shorten the start-up time of 170 min in the premise of meeting the stress requirement. It is necessary to testify the feasibility of the optimized schedule, the fatigue, creep, and creep-fatigue life of the steam turbine rotor were analyzed by continuous damage mechanics (CDM) model. The results shown that the life assessment of the rotor from the nonlinear CDM is accordance with the bilinear failure criterion of ASME Section III, and the critical creep-fatigue damage of the rotor is 0.2083, and the life loss of the rotor after working 30 years under the optimized start-up schedule is 19.25%.

Zhu-Quan Su,1,* Wei-Jie Guan,1,* Shi-Yue Li,1,* Ming Ding,2 Yu Chen,1 Mei Jiang,1 Xiao-Bo Chen,1 Chang-Hao Zhong,1 Chun-Li Tang,1 Nan-Shan Zhong1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Zhongda Hospital of Southeast University, Medical School of Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Spirometry confers limited value for identifying small-airway disorders (SADs) in early-stage COPD, which can be detected with impulse oscillometry (IOS) and endobronchial optical coherence tomography (EB-OCT). Whether IOS is useful for reflecting small-airway morphological abnormalities in COPD remains unclear. Objectives: To compare the diagnostic value of spirometry and IOS for identifying SADs in heavy-smokers and COPD based on the objective assessment with EB-OCT. Methods: We recruited 59 COPD patients (stage I, n=17; stage II, n=18; stage III–IV, n=24), 26 heavy-smokers and 21 never-smokers. Assessments of clinical characteristics, spirometry, IOS and EB-OCT were performed. Receiver operation characteristic curve was employed to demonstrate the diagnostic value of IOS and spirometric parameters. Results: More advanced staging of COPD was associated with greater abnormality of IOS and spirometric parameters. Resonant frequency (Fres) and peripheral airway resistance (R5–R20) conferred greater diagnostic values than forced expiratory volume in one second (FEV1%) and maximal (mid-)expiratory flow (MMEF%) predicted in discriminating SADs in never-smokers from heavy-smokers (area under curve [AUC]: 0.771 and 0.753 vs 0.570 and 0.558, respectively), and heavy-smokers from patients with stage I COPD (AUC: 0.726 and 0.633vs 0.548 and 0.567, respectively). The combination of IOS (Fres and R5–R20) and spirometric parameters (FEV1% and MMEF% predicted) contributed to a further increase in the diagnostic value for identifying SADs in early-stage COPD. Small airway wall area percentage (Aw% 7–9), an EB-OCT parameter, correlated significantly with Fres and R5–R20 in COPD and heavy-smokers, whereas EB-OCT parameters correlated with FEV1% and MMEF% in advanced, rather than early-stage, COPD. Conclusions: IOS parameters correlated with the degree of morphologic abnormalities of small airways assessed with EB-OCT in COPD and heavy-smokers. Fres and R5–R20 might be sensitive parameters that reliably reflect SADs in heavy-smokers and early-stage COPD. Keywords: chronic obstructive pulmonary disease, optical coherence tomography, diagnostic value, impulse oscillometry, small airway disorder

Background: Hydrogen-oxygen mixture (H2-O2) may reduce airway resistance in patients with acute severe tracheal stenosis, yet data supporting the clinical use of H2-O2 are insufficient. Objectives: To evaluate the efficacy and safety of breathing H2-O2 in acute severe tracheal stenosis. Methods: Thirty-five consecutive patients with severe acute tracheal stenosis were recruited in this prospective self-control study. Air, H2-O2 and O2 inhalation was given in 4 consecutive breathing steps: air for 15 min, H2-O2 (6 L per min, H2:O2 = 2: 1) for 15 min, oxygen (3 L per min) for 15 min, and H2-O2 for 120 min. The primary endpoint was inspiratory effort as assessed by diaphragm electromyography (EMGdi); the secondary endpoints were transdiaphragmatic pressure (Pdi), Borg score, vital signs, and impulse oscillometry (IOS). The concentration of H2 in the ambient environment was obtained with 12 monitors. Adverse reactions during the inhalation were recorded. Results: The mean reduction in the EMGdi under H2-O2 was 10.53 ± 6.83%. The EMGdi significantly decreased during 2 H2-O2 inhalation steps (Steps 2 and 4) compared with air (Step 1) and O2 (Step 3) (52.95 ± 15.00 vs. 42.46 ± 13.90 vs. 53.20 ± 14.74 vs. 42.50 ± 14.12% for Steps 1 through 4, p < 0.05). The mean reduction in the Pdi under H2-O2 was 4.77 ± 3.51 cmH2O. Breathing H2-O2 significantly improved the Borg score and resistance parameters of IOS but not vital signs. No adverse reactions occurred. H2 was undetectable in the environment throughout the procedure. Conclusions: Breathing H2-O2 may reduce the inspiratory effort in patients with acute severe tracheal stenosis and can be used for this purpose safely.

Background: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. Objectives: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. Methods: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. Results: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. Conclusions: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.

BACKGROUND: The recommended conscious sedation for bronchoscopy is still lacking. The safety and efficacy of sufentanil combined with midazolam in bronchoscopy under conscious sedation is not well elucidated. METHODS: A retrospective analysis was conducted on patients who received bronchoscopy in the First Affiliated Hospital of Guangzhou Medical University from September 2013 to July 2017. Sufentanil and midazolam were administrated for conscious sedation. The drug dosage, sedating effect and adverse event were collected and analyzed. RESULTS: Totally, 7,089 males and 4,069 females aged 54±16 years (ranged from 4 to 94 years) were enrolled in this study. The dosage of sufentanil and midazolam were 5.25±1.28 mcg (2–13 mcg) and 2.03±0.51 mg (0.5–4.5 mg), respectively. Ninety-eight point six percent (10,998/11,158) of bronchoscopies were successfully completed, while 68.7% (7,670/11,158) procedures were performed with initial dose of 5 mcg sufentanil and 2 mg midazolam. Endobronchial biopsy, transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA), therapeutic procedure and asthma were predictors of giving incremental doses of sufentanil and midazolam (all OR >1, P1, P

Background: To evaluate the diagnostic performances of detecting circulating tumor cells (CTCs) and tumor cells in bronchoalveolar lavage fluid (BALF) for peripheral lung cancer. Methods: A total of 247 patients with lung cancer and 70 cases with benign lung disease were recruited in this study. Peripheral blood and BALF samples were collected, in which the tumor cells were enriched by negative immunomagnetic selection and detected by fluorescence in situ hybridization (FISH) of chromosome enumeration probe 8 (CEP8). The levels of tumor-associated markers (e.g., CEA, CA125, and NSE) in peripheral blood plasma were measured by using electrochemiluminescence. Results: The numbers of CTCs detected in peripheral blood were significantly higher in patients with lung cancer than those with benign lung disease (5.78±0.57 vs . 1.13±0.39, Z=−8.64, P vs . 0.89±0.23, Z=−6.254, P 0.05). Detecting CTCs and tumor cells in BALF had similar areas under curves (AUC =0.871 and 0.963, respectively; P>0.05) in discriminating benign lesions from lung cancer (sensitivity 83.8% and 92.6%, specificity 86.5% and 99.9%, respectively), both of which were larger than those of NSE, CEA, and CA125 (AUC =0.564, 0.512 and 0.554, respectively; all P Conclusions: Detecting tumor cells in peripheral blood and BALF may sensitive to identify benign and malignant peripheral lung lesions and be of value for early diagnosis of lung cancer.

The convenient and effective detection of toxins is urgently demanded for food security and human health. Herein, based on the catalytic activity of mimetic peroxidase from the Cu2O@Fe(OH)3 yolk-shell nanocages, a dual-modal multi-colorimetric and ratiometric fluorescence immunosensor for the sensitive detection of ochratoxin A (OTA) was successfully developed. For the multi-colorimetric detection, H2O2 can be effectively decomposed by Cu2O@Fe(OH)3 to form ·OH groups, thus Au nanorods (Au NRs) can be etched to exhibit vivid color variations and localized surface plasmon resonance (LSPR) shifts. For the ratiometric fluorescence detection, o-phenylenediamine was oxidized by Cu2O@Fe(OH)3 to form 2,3-diaminophenazine (DAP) in the presence of H2O2. Interestingly, the exogenous fluorescence signal source of carbon dots can be quenched by DAP via inner filter effect, while a new emission peak at 563 nm can be discovered, forming a ratiometric fluorescence signal. Due to the independent signals and mutual confirmation, the performance of the dual-modal immunosensor for the detection of OTA was significantly improved, where a broad linear range from 1 ng/L to 10 μg/L with a detection limit of 0.56 ng/L (S/N = 3) was achieved. The sensing strategy was also used to monitor OTA in millet and lake water samples with a satisfied performance.