Bronchial Basaloid Papillary Tumor of Uncertain Malignant Potential: A Case Report.

Bronchial papillomas are benign tumors, which can be divided into different subtypes based on the cellular features. So far, no bronchial papilloma with basaloid cell features has been reported. We report a bronchial basaloid papillary tumor in a 67-year-old woman. Tumor recurrence and malignant transformation were observed after a long-term follow-up. The clinical, histological, immunohistochemical, and genetic features were reappraised. The primary tumor was characterized by papillary growth pattern and basaloid neoplastic cells, only a small amount of neoplastic cells showed mature characteristics. The tumor originated from respiratory epithelium and had a low proliferation index by Ki-67. Keratin (KRT) 5/6 and KRT7 showed patchy or partial positivity. Myoepithelial markers were negative. P63 was diffusely positive, but it was negative in the small amount of tumor cells with mature characteristics. The common genetic alterations (EGFR, KRAS, BRAF V600E, HER2, and ALK) of lung cancers were not detected. However, tumor recurrence was observed in the mediastinum and esophagus 12 years after surgery. The recurrent tumor had a morphology overlapping with that of the primary tumor; however, it displayed significantly malignant characteristics. The recurrent tumor was not related to high-risk HPV. A high variant allele frequency was observed in tumor suppressor gene BRCA1, TP53, oncogene GNA11, and KIT, which were all missense mutations. Considering the bland features of the primary tumor and the fact of tumor recurrence and undisputed malignant transformation, the basaloid papillary tumor was considered a tumor with uncertain malignant potential.

Peripheral T cell lymphoma initially presenting in lung biopsies: A diagnostic challenge.

BACKGROUND: Primary or secondary pulmonary involvement by peripheral T cell lymphoma (PTCL) is rare and difficult to diagnose particularly via lung biopsies. METHODS: 22 cases of PTCL diagnosed initially in lung biopsies between January 2006 and November 2020 were retrospectively reviewed followed at Nanjing Drum Tower Hospital and the First Affiliated Hospital of Zhengzhou University, respectively, including clinical manifestations, baseline biochemical indexes, images, histological findings and other available ancillary studies such as immunostaining, Epstein-Barr virus encoded RNA (EBER) in situ hybridization and T-cell receptor rearrangement analysis upon diagnosis. RESULTS: The median age of these patients was 59 years old (range: 29-82 years) at diagnosis. The majority of them complained of fever, cough and fatigue. Computed tomography scans mainly revealed multiple ill-defined nodules/masses of various sizes and densities with or without air bronchogram. Microscopically, most lesions showed lymphoid cells with clear cytoplasm and irregular nuclear contours diffusely infiltrating alveolar septa or alveolar spaces in an inflammatory background. Several cases had a predominance of small neoplastic cells (n = 4) with atypical, irregular nuclei. One case showed a diffuse monotonous pattern of growth. Angioinvasion and necrosis were not uncommon findings. The neoplastic cells in all cases were positive for one or more T-cell markers, and negative for B-cell-lineage antigens and EBER. 19 out of 22 patients had complete follow-up information, and 17 patients were dead at the last follow-up. CONCLUSIONS: Pulmonary involvement by PTCL is rare with dismal outcome. Aggressive clinical course and several clinicopathologic clues, albeit unspecific, may alert the pathologists of the possibilities of pulmonary PTCLs.

Regional anesthesia might reduce recurrence and metastasis rates in adult patients with cancers after surgery: a meta-analysis.

BACKGROUND: The influence of anesthesia techniques on cancer recurrence and metastasis following oncological surgery is a topic of growing interest. This meta-analysis investigates the potential effects of regional anesthesia (RA), either independently or combined with general anesthesia (GA), on these outcomes. METHODS: We performed an extensive search across PubMed, Embase, and the Cochrane Library databases. The primary outcome was cancer recurrence, while the secondary outcomes were local recurrence and distant metastasis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by utilizing random-effects models. The Newcastle-Ottawa Scale (NOS) was used for quality assessment of observational studies, the Cochrane Risk of Bias Tool for Randomized Trials (Rob 2.0) was used for randomized controlled trials, and all the outcomes were assessed by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: This study included 32 studies comprising 24,724 cancer patients. RA, either alone or in combination with GA, was significantly associated with reduced cancer recurrence compared to GA alone (OR = 0.82; 95% CI = 0.72 to 0.94; p < 0.01). This association remained significant for prostate cancer patients in subgroup analyses (OR = 0.71; 95% CI = 0.51 to 0.98; p = 0.04) and in the context of epidural anesthesia combined with GA. However, there were no significant associations noted for local recurrence or distant metastasis. CONCLUSIONS: This meta-analysis provides evidence that RA, used alone or adjunctively with GA, is associated with a lower risk of cancer recurrence, particularly in patients with prostate cancer. However, no significant effects were observed on local recurrence or distant metastasis. Further prospective studies should be conducted to clarify this important issue.

Associations of combined phenotypic ageing and genetic risk with incidence of chronic respiratory diseases in the UK Biobank: a prospective cohort study.

BACKGROUND: Accelerated biological ageing has been associated with an increased risk of several chronic respiratory diseases. However, the associations between phenotypic age, a new biological age indicator based on clinical chemistry biomarkers, and common chronic respiratory diseases have not been evaluated. METHODS: We analysed data from 308 592 participants at baseline in the UK Biobank. The phenotypic age was calculated from chronological age and nine clinical chemistry biomarkers, including albumin, alkaline phosphatase, creatinine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red cell distribution width and white blood cell count. Furthermore, phenotypic age acceleration (PhenoAgeAccel) was calculated by regressing phenotypic age on chronological age. The associations of PhenoAgeAccel with incident common chronic respiratory diseases and cross-sectional lung function were investigated. Moreover, we constructed polygenic risk scores and evaluated whether PhenoAgeAccel modified the effect of genetic susceptibility on chronic respiratory diseases and lung function. RESULTS: The results showed significant associations of PhenoAgeAccel with increased risk of idiopathic pulmonary fibrosis (IPF) (hazard ratio (HR) 1.52, 95% CI 1.45-1.59), COPD (HR 1.54, 95% CI 1.51-1.57) and asthma (HR 1.18, 95% CI 1.15-1.20) per 5-year increase and decreased lung function. There was an additive interaction between PhenoAgeAccel and the genetic risk for IPF and COPD. Participants with high genetic risk and who were biologically older had the highest risk of incident IPF (HR 5.24, 95% CI 3.91-7.02), COPD (HR 2.99, 95% CI 2.66-3.36) and asthma (HR 2.07, 95% CI 1.86-2.31). Mediation analysis indicated that PhenoAgeAccel could mediate 10∼20% of the associations between smoking and chronic respiratory diseases, while ∼10% of the associations between particulate matter with aerodynamic diameter <2.5 µm and the disorders were mediated by PhenoAgeAccel. CONCLUSION: PhenoAgeAccel was significantly associated with incident risk of common chronic respiratory diseases and decreased lung function and could serve as a novel clinical biomarker.

Anesthetic management of a pediatric patient with methylmalonic acidemia combined with hyperhomocysteinemia: A case report.

Methylmalonic acidemia (MMA) combined with hyperhomocysteinemia is an autosomal recessive genetic disease which can lead to metabolic acidosis, elevated lactate, and high blood ammonia level. This anesthetic management was mainly how to maintain the stable state of perioperative physiological metabolism of such patients.

Metal nanoparticles capped with plant polyphenol for oxygen reduction electrocatalysis.

The development of a convenient and universal strategy for the synthesis of inorganic-organic hybrid nanomaterials with phenolic coating on the surface is of special significance for the preparation of electrocatalysts. In this work, we report an environmentally friendly, practical, and convenient method for one-step reduction and generation of organically capped nanocatalysts using natural polyphenol tannic acid (TA) as reducing agents and coating agents. TA coated metal (Pd, Ag and Au) nanoparticles are prepared by this strategy, among which TA coated Pd nanoparticles (PdTA NPs) show excellent oxygen reduction reaction activity and stability under alkaline conditions. Interestingly, the TA in the outer layer makes PdTA NPs methanol resistant, and TA acts as molecular armor against CO poisoning. We propose an efficient interfacial coordination coating strategy, which opens up new way to regulate the interface engineering of electrocatalysts reasonably and has broad application prospects.

A case of bilateral synchronous double primary lung cancer secondary to bladder cancer: From the next-generation sequencing prospect.

One year following bladder cancer surgery, a 65-year-old man had computed tomography (CT) that revealed bilateral pulmonary nodules. Pulmonary wedge resections were performed after the nodules were found to grow in follow-up. Unusually, we found that these two lesions were not homologous, nor were they metastases from prior bladder cancer, and therefore, synchronous double primary lung cancer (sDPLC) was diagnosed. The immunohistochemical findings excluded the possibility of bladder cancer metastasis, but could not determine whether they were from the same source. Next generation sequencing (NGS) supported the diagnosis sDPLC because they amply demonstrated the two sources' distinct origins. Finally, after discussion with pathologists, this patient was diagnosed as small cell lung carcinoma (SCLC) and received postoperative EP chemotherapy. We also documented a few rather uncommon alterations that might serve as a foundation for further investigation. This case suggests that in addition to immunohistochemical, NGS is also helpful to clarify the etiology and refine the pathological classification of tumors, which has guiding significance for the establishment of precise diagnosis and optimal treatment.

Ni-doped MoS2 embedded in natural wood containing porous cellulose for piezo-catalytic degradation of tetracycline.

Wood is a natural material with low cost and easy recovery, which porous, layered, excellent structure and mechanical properties make it possible to apply in wastewater treatment. We have successfully grown MoS2 on natural wood containing porous cellulose and introduced the high conductivity circuit path provided by Ni nanoparticles to construct a new piezoelectric three-dimensional wood block for the efficient degradation of tetracycline. Ni/MoS2/Wood exhibited excellent piezo-catalytic degradation performance, and the degradation rate of tetracycline reached 95.96 % (k = 0.0411 min-1) under ultrasonic vibration. After 5 cycles, the degradation rate still reached 90.20 %. In addition, Ni/MoS2/Wood was used as the reactor filler to degrade tetracycline through piezoelectric response triggered by hydrodynamic force, and the degradation rate reached 90.27 % after 60 min. Further, the mechanism and the possible degradation pathways of tetracycline degradation were proposed. This low-cost, recyclable and stable three-dimensional wood block piezoelectric material provides a new idea for the practical application of wastewater treatment.

Downregulation of Nrf2 in the Hippocampus Contributes to Postoperative Cognitive Dysfunction in Aged Rats by Sensitizing Oxidative Stress and Neuroinflammation.

Postoperative cognitive dysfunction (POCD) is a recognized clinical complication defined by a new cognitive impairment arising after a surgical procedure. Elderly patients are especially vulnerable to cognitive impairment after surgical operations, but the underlying mechanisms remain elusive. Oxidative stress and neuroinflammation in the hippocampus, a brain region involved in memory formation, are considered as major contributors to the development of POCD. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of endogenous inducible defense system, plays a crucial role in protecting cells against oxidative stress and inflammation by enhancing transcription of antioxidant and anti-inflammatory target genes. Here, we examined whether aging downregulates Nrf2 in the hippocampus and, if so, whether downregulation of hippocampal Nrf2 contributes to POCD in aging. Young and aged rats underwent abdominal surgery or sham operation. One week later, cognitive function was assessed, and brains were collected for molecular studies. Compared with young sham rats, aged sham rats exhibited a significant reduction in expression of Nrf2 in the hippocampus. Interestingly, the expression of Nrf2 downstream target genes and levels of reactive oxygen species (ROS) and proinflammatory cytokines in the hippocampus as well as cognitive function were comparable between aged sham and young sham rats. After abdominal surgery, young rats showed significant upregulation of Nrf2 and its target genes in the hippocampus. However, aged rats did not show changes in expression of Nrf2 and its target genes but had increased levels of ROS and proinflammatory cytokines in the hippocampus, along with cognitive impairment as indicated by reduced contextual freezing time. Moreover, upregulation of hippocampal Nrf2 in aged rats with intracerebroventricular infusion of a Nrf2 activator reduced levels of ROS and proinflammatory cytokines in the hippocampus, ameliorating cognitive dysfunction after surgery. The results suggest that aging-induced downregulation of Nrf2 in the hippocampus causes the failure to activate Nrf2-regulated antioxidant defense system in response to surgical insult, which contributes to POCD by sensitizing oxidative stress and neuroinflammation. Nrf2 activation in the brain may be a novel strategy to prevent the cognitive decline in elderly patients after surgery.

Mast cell stabilizer disodium cromoglycate improves long-term cognitive impairment after general anesthesia exposure in neonatal mice.

Background: Prolonged exposure to general anesthesia (GA) results in long-lasting cognitive impairment, especially during critical stages of brain development. An exaggerated neuroinflammation induced by anesthesia is generally considered to be a key cause of cognitive impairment. Materials and methods: Postnatal day 7 (PND 7) mice were exposed to GA by isoflurane inhalation for 6 h or mock anesthesia. Disodium cromoglycate (DSCG) was intraperitoneally injected daily for 2 weeks, beginning from 30 min before anesthesia. The post-anesthesia evaluation included behavioral tests, toluidine blue staining, immunofluorescence and western blot. Results: Our results demonstrated the long-term cognition were impaired after 6 h GA exposure in neonatal mice. DSCG treatment ameliorated early mast cells (MCs) degranulation and mast cell tryptase (MCT) expression, which helps to attenuate subsequent neuroinflammation, activation of microglia and astrocytes, and damage to oligodendrocytes and synapses to improve cognitive impairment. Conclusion: Disodium cromoglycate could effectively improve long-term cognitive impairment after GA exposure in neonatal mice.

Elevated Expression of Growth Differentiation Factor-15 Is Associated With Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

Backgrounds: Growth differentiation factor 15 (GDF-15) is a highly divergent member of the TGF-ß superfamily and has been implicated in various biological functions. However, the expression of GDF-15 in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is unclear. Method: The study included 47 AE-IPF patients, 61 stable IPF (S-IPF) subjects, and 31 healthy controls (HCs). Serum GDF-15 levels and their expression in the lung were measured. The correlation between serum GDF-15 and other clinical parameters and the risk factors for AE occurrence and the survival of IPF patients were analyzed. Results: Serum GDF-15 levels were significantly elevated in AE-IPF patients (1279.22 ± 540.02 pg/ml) as compared with HCs (891.30 ± 479.90 pg/ml) or S-IPF subjects (107.82 ± 14.21 pg/ml) (both p < 0.001). The protein and mRNA expressions of GDF-15 in the lung of AE-IPF patients were significantly increased as compared with S-IPF cases (p = 0.007 and p = 0.026, respectively). The serum GDF-15 level was correlated with the clinical variables of inflammation, metabolism, and disease severity in IPF subjects (all p < 0.05). The GDF-15 serum concentration was significantly higher in decedents than in survivors (p = 0.005). A serum GDF-15 level above 989.3 pg/ml was a risk factor for AE occurrence (p = 0.04), and the level above 1,075.76 pg/ml was an independent predictor for survival in IPF cases (p = 0.007). Conclusions: The GDF-15 level was significantly elevated in subjects with AE-IPF. GDF-15 could be a promising biomarker for AE occurrence and survival in IPF patients.

Progressive lymphocytosis in familial hemophagocytic lymphohistiocytosis with lymphocytic interstitial pneumonia: a case report.

Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder which is less typical in adults than pediatric patients. In this study, we reported a rare case of adult-onset FHL3 with progressive lymphocytosis and lymphocytic interstitial pneumonia (LIP). A 20-year old female was admitted to our institution for persistent cough with fever. A chest high-resolution computed tomography (HRCT) scan showed diffuse bilateral ground glass opacities (GGO). A lung biopsy revealed infiltration of lymphocyte in the pulmonary interstitium. The patient was treated with corticosteroids and immunosuppressants, followed by significant clinical improvement although lymphocytosis still persisted. The definitive diagnosis of FHL was based on whole genome sequencing by which heterozygous mutations in UNC13D gene were identified. Lymphocytosis may be a remarkable feature of some patients with FHL. Performing gene sequencing is important to improve the recognition of FHL to avoid misdiagnosis.

Protective function of interleukin-22 in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor-beta (TGF-ß) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin-22 (IL-22) in the pathogenesis of IPF by regulating the TGF-ß pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL-22R knock out (IL-22RA1-/- ) and IL-22 supplementation mouse models were used to determine if IL-22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL-22 and/or TGF-ß1. In a clinical cohort, the expression level of IL-22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL-22 expression was associated with poorer pulmonary function. IL-22R-/- mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL-22 augmentation by intranasal instillation of recombinant IL-22 repressed inflammation and fibrotic phenotype. In vitro, IL-22 treatment repressed TGF-ß1 induced gene markers representing epithelial-mesenchymal-transition and fibroblast-myofibroblast-transition, likely via the inhibition of TGF-ß receptor expression and subsequent Smad2/3 activation. IL-22 appears to be protective against pulmonary fibrosis by inhibiting TGF-ß1 signaling, and IL-22 augmentation may be a promising approach to treat IPF.

Development of local anesthetic drug delivery system by administration of organo-silica nanoformulations under ultrasound stimuli: in vitro and in vivo investigations.

The development of local anesthetic (LA) system is the application of commercial drug for the pain management that indorses the reversible obstructive mechanism of neural transmission through preventing the innervation process in human peripheral nerves. Ropivacaine (RV) is one of the greatest frequently used LA s with the actions of long-lasting and low-toxicity for the post-operative pain management. In this work, we have approached novel design and development of glycosylated chitosan (GCS) encapsulated mesoporous silica nanoparticles (GCS-MONPs)-based nano-scaffold for sustainable distributions and controlled/supported arrival of stacked RV for targeting sites, which can be activated by either outer ultrasound activating to discharge the payload, foundation on-request and dependable analgesia. The structural and morphology analyses result established that prepared nano-formulations have successful molecular interactions and RV loaded spherical morphological structures. The drug release profile of developed nanostructure with ultrasound-activation has been achieved 50% of drug release in 2 h and 90% of drug release was achieved in 12 h, which displays more controlled release when compared to free RV solution. The in vitro cell compatibility analysis exhibited GCS-MONPs with RV has improved neuron cell survival rates when compared to other samples due to its porous surface and suitable biopolymer proportions. The analysis of ex vitro and in vivo pain relief analysis demonstrated treated animal models have high compatibility with GCS-MONPs@RV, which was confirmed by histomorphology. This developed MONPs based formulations with ultrasound-irradiation gives a prospective technique to clinical agony the board through on-request and dependable help with discomfort.

Respiratory traits and coal workers' pneumoconiosis: Mendelian randomisation and association analysis.

OBJECTIVES: Susceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker's pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies. METHODS: To systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study. RESULTS: Interestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10-4) and lung function (rs4651005, OR=1.39, p=1.62×10-3; rs985256, OR=0.73, p=8.24×10-4 and rs6539952, OR=1.28, p=4.32×10-4) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of FAM13A (rs2609255, p=7.4 ×10-4), ANGPTL1 (rs4651005, p=5.4 ×10-7), SPATS2L (rs985256, p=1.1 ×10-5) and RP11-463O9.9 (rs6539952, p=7.1 ×10-6) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis. CONCLUSIONS: These results provided a deeper understanding of the genetic predisposition basis of CWP.

Surfactant protein D is associated with 3-month mortality of anti-MDA5 antibody-interstitial lung disease.

OBJECTIVES: To investigate the associations between serum levels of matrix metalloproteinase 7 (MMP7), surfactant protein D (SPD), interleukin 18 (IL-18) and chemokine ligand 18 (CCL18) with dermatomyositis and polymyositis-associated interstitial lung disease (DM/PM-ILD) and evaluate their prognostic values in the disease. METHODS: Seventy-eight patients with multiple disciplinary team diagnosis of DM/PM-ILD were enrolled and classified as anti-melanoma differentiation-associated protein 5 antibody (MDA5)-ILD, anti-synthetase antibodies (ARS)-ILD and other antibodies-ILD upon autoantibodies profiles. Clinical data were collected and serum levels of four biomarkers were analysed. The primary endpoint was 3-month mortality. The cut-off values of biomarkers for mortality were figured out by receiver operating characteristic (ROC) analysis. Cox regression was performed to evaluate predictive values. RESULTS: Serum levels of MMP7 (p=0.036), SPD (p<0.001), IL-18 (p<0.001) and CCL18 (p<0.001) in patients with DM/PM-ILD were significantly higher than healthy controls with levels of MMP7 (p=0.029) and SPD (p=0.029) in patients with MDA5-ILD significantly lower than patients with ARS-ILD. The 3-month mortality in MDA5-ILD was 54.5% (12/22). Multivariate analysis showed that age (p=0.001, HR 1.151, 95% CI 1.063-1.247) and an increased level of SPD (>75.90ng/ml, p=0.005, HR 16.411, 95% CI 2.369-113.711) were significant predictors for 3-month mortality in patients with MDA5-ILD. CONCLUSIONS: Elevated serum biomarkers were associated with DM/PM-ILD with differential levels between MDA5-ILD and ARS-ILD. Age and an increased SPD had prognostic values for predicting short-term mortality in patients with MDA5-ILD. Our study was important in providing a clue for understanding the classification and prognosis of DM/PM-ILD.