A novel method for precise implantation of tracheal Y-shaped stent.

The tracheal Y-shaped stent is mainly used for the treatment of critical patients with airway stenosis or esophagotracheal fistula near carina. A novel method for precise implantation of Y-shaped tracheal stents was developed using double-lumen endotracheal intubation and flexible bronchoscopy. This approach aims to address the limitations associated with X-ray or rigid bronchoscopy guidance, such as operational difficulties and the risk of inaccurate stent placement leading to implantation failure or suffocation. With this new technique, 13 tracheal Y-shaped stents were successfully implanted. This method shows promise in reducing the complexity of stent implantation and facilitating timely treatment for patients in need. Additionally, it has the potential to update current operating standards and guidelines for this procedure.

Characteristics and prognostic implications of peripheral blood lymphocyte subsets in patients with anti-MDA5 antibody positive dermatomyositis-interstitial lung disease.

OBJECTIVES: To examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients. METHODS: Data were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5+ DM-ILD) and anti-MDA5 antibody negative group (MDA5- DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5+ DM-ILD. RESULTS: Out of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5+ and 194 were anti-MDA5-. Peripheral blood lymphocyte count, CD3+ count, percentage of CD3+, CD3+CD4+ count, and CD3+CD8+ count was lower in MDA5+ DM-ILD than in MDA5- DM-ILD- (all P < 0.001) as well as CD3-CD19+ count (P = 0.04). In MDA5+ DM-ILD, CD3+CD8+ count ≤ 49.22 cell/µL (HR = 3.81, 95%CI [1.20,12.14]) and CD3-CD19+ count ≤ 137.64 cell/µL (HR = 3.43, 95%CI [1.15,10.24]) were independent predictors of mortality. CD3+CD8+ count ≤ 31.38 cell/µL was associated with a higher mortality risk in all DM-ILD patients (HR = 8.6, 95%CI [2.12,31.44]) after adjusting for anti-MDA5 and other clinical characteristics. CONCLUSION: Significant lymphocytes decrease was observed in MDA5+ DM-ILD patients. CD3+CD8+ cell count was associated with worse prognosis in both MDA5+ DM-ILD and all DM-ILD patients.

Tetrabutylammonium Halides as Selectively Bifunctional Catalysts Enabling the Syntheses of Recyclable High Molecular Weight Salicylic Acid-Based Copolyesters.

To synthesize high molecular weight poly(phenolic ester) via a living ring-opening polymerization (ROP) of cyclic phenolic ester monomers remains a critical challenge due to serious transesterification and back-biting reactions. Both phenolic ester bonds in monomer and polymer chains are highly active, and it is difficult so far to distinguish them. In this work, an unprecedented selectively bifunctional catalytic system of tetra-n-butylammonium chloride (TBACl) was discovered to mediate the syntheses of high molecular weight salicylic acid-based copolyesters via a living ROP of salicylate cyclic esters (for poly(salicylic methyl glycolide) (PSMG), Mn =361.8 kg/mol, Ð<1.30). Compared to previous catalysis systems, the side reactions were suppressed remarkably in this catalysis system because phenolic ester bond in monomer can be selectively cleaved over that in polymer chains during ROP progress. Mechanistic studies reveal that the halide anion and alkyl-quaternaryammonium cation work synergistically, where the alkyl-quaternaryammonium cation moiety interacts with the carbonyl group of substrates via non-classical hydrogen bonding. Moreover, these salicylic acid-based copolyesters can be recycled to dimeric monomer under solution condition, and can be recycled to original monomeric monomers without catalyst under sublimation condition.

Clinical characteristics and therapeutic effects of checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.

BACKGROUND: With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. METHODS: The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. RESULTS: 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. CONCLUSION: We found that glucocorticoid 1-2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.

Tertiary lymphoid structures in lung adenocarcinoma: characteristics and related factors.

OBJECTIVE: Tertiary lymphoid structures (TLSs) are found in a variety of malignancies and affect the growth of tumors, but few studies have addressed their role in lung adenocarcinoma (LAC). We aimed to evaluate clinical features associated with TLSs in patients with LAC. METHODS AND MATERIALS: A collection of resected pulmonary nodules in patients with LAC was retrospectively analyzed. TLSs were quantified by their number per square millimeter tumor area (density) and by the degree of lymphocyte aggregation (maturity) in each case. The correlation between TLS density and maturity and clinical features was calculated. RESULTS: A total of 243 patients were selected, of whom 219 exhibited TLSs. The occurrence of TLSs was correlated with computed tomography (CT) features as follows: pure ground-glass nodules (pGGNs) (n = 43) was associated with a lower occurrence rate than part-solid nodules (PSNs) (n = 112) and solid nodules (SNs) were (n = 88) (p = 0.037). TLS density was correlated with age and CT features. Poisson regression showed higher TLS density in PSNs and SNs than in pGGNs (incidence rate ratio [IRR]: 3.137; 95% confidence interval [CI]: 1.35-7.27; p = 0.008 and IRR: 2.44; 95% CI: 1.02-5.85; p = 0.046, respectively). In addition, TLS density was higher in patients aged under 60 years than in those aged over 60 years (IRR: 0.605; 95% CI: 0.4-0.92; p = 0.018). The maturity of TLSs was higher in patients with higher tumor stages (p = 0.026). CONCLUSIONS: We demonstrated distinct profiles of TLSs in early LAC and their correlations with CT features, age, and tumor stages, which could help understand tumor progression and management.

Radiographic features and prognosis of early- and late-onset non-small cell lung cancer immune checkpoint inhibitor-related pneumonitis.

BACKGROUND: Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis. METHODS: We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP. RESULTS: CIP had an incidence of 4.7%, a median onset time of 10 weeks, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥ 3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥ 3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P < 0.05). CONCLUSION: Early-onset CIP cases were higher in the Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade and mainly presented with an OP-like radiographic pattern; whereas, late-onset CIP cases were lower in CTCAE grade and mainly presented with an NSIP-like radiographic pattern. Finally, the prognosis of the early-onset CIP group was poorer than that of the late-onset CIP group. We believe that this study will be helpful for clinicians for making early diagnosis and deciding treatment modalities for patients with CIP.

Neutrophil-lymphocyte ratio (NLR) predicted prognosis for advanced non-small-cell lung cancer (NSCLC) patients who received immune checkpoint blockade (ICB).

Purpose: The aim of this study was to identify the prognostic value of blood neutrophil-lymphocyte ratio (NLR) in patients with advanced non-small-cell lung cancer (NSCLC) who received immune checkpoint blockade (ICB) therapy. Materials and methods: 147 advanced NSCLC patients were enrolled in this study from June 30, 2013, to August 30, 2017. Survival analysis used the Kaplan and Meier methodology. The mean follow-up time was 2.6 years. The phenotypic T cells subtypes were evaluated by flow cytometry. Results: Of these patients, receiver operating characteristic (ROC) curves analysis were used to confirm the cut-off value, and patients were stratified into NLR>2.5 (n=88) and NLR≤2.5 (n=59) groups. Survival analysis showed that patients with NLR≤2.5 had significantly favorable overall survival (OS) and progression-free survival (PFS) compared with patients with NLR>2.5. After stratified with the tumor mutational burden (TMB), we further found that patients with NLR≤2.5 had significantly favorable OS and PFS compared with patients with NLR>2.5 in the group of patients with TMB>10, while in group patients with TMB≤10, patients with NLR≤2.5 had no significantly favorable OS and PFS compared with patients with NLR>2.5. The CD3+ and CD8+/CD28+ T cell subsets were significantly increased in patients with NLR≤2.5 (P<0.05), while the CD8+/CD28- and CD4+/CD25+ cell subsets were significantly decreased in patients with NLR≤2.5 (P<0.05). Conclusion: High NLR value independently predicted poorer survival in advanced NSCLC patients received ICB therapy. The NLR may help oncologists to predict outcomes of patients received ICB and choose alternative therapies for patients with high NLR value.

Antibody to mCLCA3 suppresses symptoms in a mouse model of asthma.

BACKGROUND: Asthma is a complex and heterogeneous chronic inflammatory disorder that is associated with mucous cell metaplasia and mucus hypersecretion. Functional genomic analysis indicates that mucous cell metaplasia and mucus hypersecretion depend on members of the calcium-activated chloride channel (CLCA) gene family. It has been reported that the inhibition of CLCAs could relieve the symptoms of asthma. Thus, the mCLCA3 antibody may be a promising strategy to treat allergic diseases such as asthma. METHODS: We constructed asthmatic mouse models of OVA-induced chronic airway inflammatory disorder to study the function of the mCLCA3 antibody. Airway inflammation was measured by HE staining; goblet cell hyperplasia and mucus hypersecretion were detected by PAS staining; muc5ac, IL-13, IFN-γ levels in bronchoalveolar lavage fluid (BALF) were examined by ELISA; Goblet cell apoptosis was measured by TUNEL assay and alcian blue staining; mCLCA3, Bcl-2 and Bax expression were detected by RT-PCR, Western blotting and immunohistochemical analysis. RESULTS: In our study, mice treated with mCLCA3 antibody developed fewer pathological changes compared with control mice and asthmatic mice, including a remarkable reduction in airway inflammation, the number of goblet cells and mCLCA3 expression in lung tissue. The levels of muc5ac and IL-13 were significantly reduced in BALF. We also found that the rate of goblet cell apoptosis was increased after treatment with mCLCA3 antibody, which was accompanied by an increase in Bax levels and a decrease in Bcl-2 expression in goblet cells. CONCLUSIONS: Taken together, our results indicate that mCLCA3 antibody may have the potential as an effective pharmacotherapy for asthma.

Induction of angiogenesis by controlled delivery of vascular endothelial growth factor using nanoparticles.

AIMS: The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex-GMA) and gelatin for therapeutic angiogenesis. METHODS: The nanoparticles were prepared using phase separation method, and the drug release profile was determined by ELISA study. The bioactivity of VEGF-incorporated nanoparticles (VEGF-NPs) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single-photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry. RESULTS: The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130 ± 3.5 nm. The VEGF encapsulated was released in a biphase manner, with the majority of 69% released over 1-12 days. Tube formation assays showed increased tubular structures by VEGF-NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF-NP significantly increased blood perfusion compared with empty nanoparticles (both P < 0.001), but it was much higher in VEGF-NP-treated limbs (P < 0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF-NP-treated limbs. CONCLUSIONS: Dex-GMA and gelatin-based nanoparticles could provide sustained release of VEGF and may serve as a new way for angiogenesis.

A graphene-based electrochemical sensor for sensitive determination of caffeine.

An electrochemical sensor based on the electrocatalytic activity of graphene (Gr) for sensitive detection of caffeine is presented. The electrochemical behaviors of caffeine on Nafion-Gr modified glassy carbon electrode (Nafion-Gr/GCE) were investigated by cyclic voltammetry and differential pulse voltammetry. The results showed that the Nafion-Gr/GCE exhibited excellent electrocatalytic activity to caffeine. Caffeine can be effectively accumulated at Nafion-Gr/GCE and produce a sensitive anodic peak. Such electrocatalytic behavior of Gr is attributed to its unique physical and chemical properties, e.g., subtle electronic characteristics and strong adsorptive capability. This electrochemical sensor shows an excellent performance for detecting caffeine with a detection limit of 1.2×10(-7) M (S/N=3), a reproducibility of 5.2% relative standard deviation, and a satisfied recovery from 98.6% to 102.0%. The sensor shows great promise for simple and sensitive determination of caffeine.