Quantitative proteomics revealed protein biomarkers to distinguish malignant pleural effusion from benign pleural effusion.

To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000，with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values. SIGNIFICANCE: We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4-12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.

Clinical characteristics and outcomes of pleural aspergillosis: a review of 13 cases.

Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), which mostly occurs in the immunocompromised host. The clinical condition is critical, especially to those who develop bronchopleural fistula. This study aimed to assess the characteristics and the prognosis of aspergillus pleurisy. Clinical data from 13 patients diagnosed with aspergillus pleurisy in our hospital from January 2000 to December 2022 were retrospectively studied. Thirteen patients with Aspergillus pleurisy were included. There were 10 males and 3 females, with a median age of 65 (range: 18-79) years. Bronchopleural fistula was present in eight patients. A proven diagnosis of Aspergillus pleurisy was based on positive pleural fluid culture in seven cases and histopathological examination of pleural biopsies in six cases. Four patients refused further treatment and were discharged from the hospital against medical advice. Nine cases recovered and were discharged after multiple antifungal treatments (systemic and topical antifungal therapies, pleural drainage and irrigation, and surgical repair). During follow-up, one patient, who suffered underlying bronchiectasis, died of massive hemoptysis 2 years after discharge. The remaining eight cases are still under close follow-up, with a median follow-up of 5.4 (range: 1.3-18.9) years. The prognosis of aspergillus pleurisy complicated with bronchopleural fistula is poor. Thoracic surgery, especially lung resection, is a risk factor associated with the incidence of Aspergillus pleurisy. Systemic antifungal therapy and adequate pleural irrigation could improve the prognosis. IMPORTANCE: Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), associated with a poor prognosis. The morbidity and mortality of this condition have not been thoroughly studied, and recent research on this topic is limited. The current study included 13 patients diagnosed with Aspergillus pleurisy, with the majority presenting concomitantly with a bronchopleural fistula. Among these patients, nine had a history of thoracic surgery, including lung transplantation and lobectomy. Four patients refused further treatment and were discharged against medical advice, while one patient succumbed to massive hemoptysis 2 years after discharge. This case series provides essential insights into Aspergillus pleurisy and evaluates the therapeutic strategy based on a limited cohort.

Extracellular Vesicles Obtained From Lung Adenocarcinoma Cells Cultured Under Intermittent Hypoxia Induce M2 Macrophage Polarization via miR-20a-5p Delivery.

Conclusion: These findings indicate that EVs obtained from lung adenocarcinoma cells cultured under IH deliver miR-20a-5p to promote M2 macrophage polarization by targeting PTEN.

Arsenic-Induced Ferroptosis in Chicken Hepatocytes via the Mitochondrial ROS Pathway.

Arsenic has been shown to be highly toxic and can cause liver damage. Previous studies have shown that arsenic causes severe liver damage and induces accumulation of reactive oxygen species (ROS). This study aimed to investigate the effects of ferroptosis on the liver in arsenic trioxide (ATO) and to explore the underlying mechanisms. We confirmed the hepatotoxic effects of arsenic by in vivo and in vitro experiments. After 28 days of administration of arsenic trioxide (4-mg/kg, 8-mg/kg) by gavage, chickens exhibited body weight loss and liver damage in a dose-dependent manner. In addition, in vivo and in vitro western blot and real-time fluorescence quantitative PCR analyses simultaneously indicated that ferroptosis might be the main pathway of arsenic-induced liver injury. Finally, Mito-TEMPO effectively eliminated the ROS accumulation in mitochondria, significantly attenuating the process of cellular ferroptosis. In summary, the hepatotoxic effects of arsenic are related to ferroptosis, and the hepatic ferroptosis process of arsenic is regulated by mitochondrial ROS (MtROS). Our study reveals new mechanisms of arsenic toxicity to the liver, which may deepen our understanding of arsenic toxicology.

Curcumin alleviates AFB1-induced nephrotoxicity in ducks: regulating mitochondrial oxidative stress, ferritinophagy, and ferroptosis.

Aflatoxin B1 (AFB1), an extremely toxic mycotoxin that extensively contaminates feed and food worldwide, poses a major hazard to poultry and human health. Curcumin, a polyphenol derived from turmeric, has attracted great attention due to its wonderful antioxidant properties. Nevertheless, effects of curcumin on the kidneys of ducks exposed to AFB1 remain unclear. Additionally, the underlying mechanism between AFB1 and ferroptosis (based on excessive lipid peroxidation) has not been sufficiently elucidated. This study aimed to investigate the protective effects and potential mechanisms of curcumin against AFB1-induced nephrotoxicity in ducklings. The results indicated that curcumin alleviated AFB1-induced growth retardation and renal distorted structure in ducklings. Concurrently, curcumin inhibited AFB1-induced mitochondrial-mediated oxidative stress by reducing the expression levels of oxidative damage markers malondialdehyde (MDA) and 8-hydroxy-2 deoxyguanosine (8-OHdG) and improved the expression of mitochondria-related antioxidant enzymes and the Nrf2 pathway. Notably, curcumin attenuated iron accumulation in the kidney, inhibited ferritinophagy via the NCOA4 pathway, and balanced iron homeostasis, thereby alleviating AFB1-induced ferroptosis in the kidney. Collectively, our results suggest that curcumin alleviates AFB1-induced nephrotoxicity in ducks by inhibiting mitochondrial-mediated oxidative stress, ferritinophagy, and ferroptosis and provide new evidence for the mechanism of AFB1-induced nephrotoxicity in ducklings treated with curcumin.

Curcumin attenuates AFB1-induced duck liver injury by inhibiting oxidative stress and lysosomal damage.

Aflatoxin B1 (AFB1), as the most toxic secondary metabolite produced by Aspergillus flavus, is a serious threat to human and animal health. Curcumin, a polyphenol from the plant turmeric, has demonstrated unique anti-damage properties in several studies. But, its ability to alleviate AFB1-induced liver damage in ducks and the underlying mechanisms are not completely elucidated. In this study, we investigated the intervention of curcumin on AFB1-induced hepatotoxicity in ducks. Research data showed that the combination of curcumin and AFB1 alleviated oxidative stress, reduced malondialdehyde (MDA) accumulation and relieved hepatotoxicity after 28 days of treatment, compared with AFB1. Also, curcumin upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzymes (SOD, HO-1), which enhanced the antioxidant capacity of the liver. In addition, curcumin inhibited AFB1-induced lysosomal damage in the liver, with the character of reduced lysosomal membrane permeabilization, restored autophagic flux, and promoted lysosomal biogenesis, thereby enhancing the self-protective capacity of the liver. In conclusion, our results suggest that curcumin alleviates AFB1-induced duck hepatotoxicity by inhibiting oxidative stress and lysosomal damage.

Venous malformation presenting as Mauritia arabica-like bronchial wall thickness: a case report.

Primary pulmonary venous malformation is rare and usually presents as single or multiple round masses or nodules. Here, we present the first report of a case of venous malformation presenting as Mauritia arabica-like bronchial wall thickness that was initially misdiagnosed as bronchiectasis. A Chinese man in his late 20s presented complaining of hemoptysis for 10 days. Computed tomography demonstrated bronchiectasis and M. arabica-like bronchial wall thickening in the left lower lobe. He was unresponsive to medical treatment for bronchiectasis and underwent thoracoscopic left lower lobectomy. Histopathological examination revealed venous malformation around the bronchial walls with no bronchiectasis. Venous malformation should be considered in the differential diagnosis of bronchiectasis, especially in patients with the following triad of signs: no response to antibiotics, M. arabica-like bronchial wall thickness, and normal accompanying arteries.

Clinical diagnosis and etiology of patients with Chlamydia psittaci pneumonia based on metagenomic next-generation sequencing.

The incidence of severe Chlamydia psittaci (C. psittaci) pneumonia and coinfections is increasing. Early detection of this condition is needed to prevent negative outcomes, along with detailed descriptions of its associated clinical characteristics. Our study contributes by undertaking etiological analysis of patients with C. psittaci pneumonia based on metagenomic next-generation sequencing (mNGS). A retrospective analysis of 30 patients with C. psittaci pneumonia was undertaken and confirmed by mNGS or polymerase chain reaction (PCR). Clinical manifestations of the severe and non-severe C. psittaci pneumonia groups were compared for clinical reference. Etiological analyses were also performed to comprehensively understand pathogeny and coinfection with other respiratory pathogens in C. psittaci patients. The absolute value of lymphocytes (LYM) in the severe group was lower than in the non-severe group. At the same time, neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), alanine aminotransferase (ALT), D-II polymer, brain natriuretic peptide (BNP), myoglobin (MYO), and cardiac troponin I (cTnI) were significantly higher (P < 0.05) in the severe group. mNGS has a broader pathogen spectrum and can more sensitively detect C. psittaci and other low-abundance pathogens with a higher positive detection rate (100%, 13/13 vs. 46%, 6/13, P <0.05) than conventional culture methods. mNGS detected the following dominant species associated with C. psittaci in patients: bacteria (53.2%, 39% gram-positive, 61% gram-negative), fungi (12.9%), and viruses (33.9%). A total of 73.3% (11/15) of patients had suspected coinfections, with a coinfection rate of 91.7% (11/12) in the severe group. No coinfection or death occurred in the non-severe group. Prognosis in the severe group was poor, with a mortality rate of 27.3% (3/11) for patients with coinfection. Eight of 11 patients with coinfections (72.7%) recovered. In conclusion, the clinical symptoms of severe C. psittaci pneumonia manifested as abnormal inflammatory indicators, impaired liver function, myocardial injury, coagulation, and relatively low immune responses. The higher proportion of patients with coinfections in our study supports the use of mNGS for comprehensive early detection of respiratory infections in patients with C. psittaci pneumonia. Simultaneous early identification of coinfections would further improve the clinical treatment of these patients.

CDCA4 as a novel molecular biomarker of poor prognosis in patients with lung adenocarcinoma.

Background: Because of the high incidence and poor prognoses of lung adenocarcinoma (LUAD), it is essential to identify cost-effective treatment options and accurate and reliable prognostic biomarkers. CDCA4 upregulation has been identified in many cancers. However, the prognostic importance of CDCA4 and its role in LUAD remain unknown. Methods: CDCA4 expression was assessed through IHC, Western blotting (WB) and RT-PCR. The Cancer Genome Atlas (TCGA) provided data from 513 patients to study the expression and prognostic relevance of CDCA4 in LUAD. This study used gene set enrichment analyses (GSEA), gene ontology and KEGG pathway analyses for elucidating potential mechanisms underpinning the function of CDCA4 in LUAD. We also investigated correlations between immune infiltration and CDCA4 expression with single specimen GSEA (ssGSEA). Results: According to database analysis and identification of patient tissue samples, CDCA4 expression in tumour tissues surpassed that in normal tissues (P< 0.001). Increased CDCA4 expression was positively correlated with a higher T, N, pathologic stage and poor primary therapy outcome. In addition, the Kaplan-Meier plotter exhibited that an elevated CDCA4 expression was related to worse disease-specific survival(DSS) and overall survival (OS) (DSS HR= 5.145, 95% CI=3.413-7.758, P<0.001; OS HR=3.570, 95% CI=2.472-5.155, P<0.001). Then multivariate COX regression analyses indicated that the CDCA4 gene was an independent risk consideration for prognoses. GO and KEGG results showed that CDCA4 and its neighbouring genes were enriched in the cell cycle and DNA replication. As determined by GSEA, CDCA4 was related to various immune-related signalling pathways (SPs), Homologous recombination, DNA replication and the cell cycle. SsGSEA analysis showed a significant association between CDCA4 expression and Th2 cells, mast cells, eosinophils and Th17 cells. Conclusions: CDCA4 expression is increased in LUAD and is a potential predictive biomarker and therapeutic target.

Myostatin is involved in skeletal muscle dysfunction in chronic obstructive pulmonary disease via Drp-1 mediated abnormal mitochondrial division.

Background: Skeletal muscle dysfunction (SMD) is one of the most prominent extrapulmonary effects of chronic obstructive pulmonary disease (COPD). Myostatin negatively regulates the growth of skeletal muscle. We confirmed that myostatin expression is significantly increased in the quadriceps femoris muscle tissue of rats with COPD and is involved in the development of SMD in COPD, but the mechanism by which this occurs has yet to be uncovered. Dynamin-related protein 1 (Drp-1) has been shown to promote apoptosis and affect cellular energy metabolism by mediating enhanced mitochondrial division. Preliminary findings from our group illustrated that mitochondrial division and Drp-1 expression were increased in COPD quadriceps femoris cells. However, it is not yet clear whether mitochondrial dynamics are affected by myostatin in COPD quadriceps myocytes. Methods: The study sought to explore the effects and potential mechanisms of myostatin on skeletal muscle atrophy, mitochondrial dynamics, apoptosis, and the links between related processes in COPD. Results: Our findings showed that cigarette smoke exposure stimulated an increase in myostatin, increased superoxide production, decreased mitochondrial membrane potential, significantly promoted Drp-1-mediated mitochondrial fission, and promoted apoptosis. Conclusions: In summary, our study demonstrated that cigarette smoke led to increased Drp-1 expression and enhanced mitochondrial division by upregulating myostatin, which in turn promoted apoptosis and affected cellular energy metabolism, leading to the development of SMD in COPD. This study extends understandings of skeletal muscle function in COPD and provides a basis for the use of myostatin and Drp-1 as novel therapeutic targets for SMD in COPD.

The interaction among OSA, CPAP, and medications in patients with comorbid OSA and cardiovascular/cerebrovascular disease: a randomized controlled trial.

BACKGROUND: Most patients with comorbid sleep apnea (OSA), cardiovascular (CV) disease, and/or cerebrovascular (CeV) disease simultaneously take medications. Whether OSA and continuous positive airway pressure (CPAP) interact with CV/CeV medications remains unknown. This study aimed to determine the interaction among OSA, CPAP, and CV/CeV medications; the effects of medications on major adverse cardiac and cerebrovascular events, and survival in patients with comorbid OSA and CV/CeV. METHODS: This was a post hoc analysis of the data from one center of the Sleep Apnea Cardiovascular Endpoints Study. Participants (aged 45-75 years) with comorbid OSA and CV/CeV were randomized to receive usual care with or without CPAP from December 2008 to November 2013. The primary endpoint was death and the secondary endpoint was a composite of death, myocardial infarction, stroke, hospitalization for unstable angina, heart failure, and transient ischemic attack. RESULTS: In total, 131 patients were analyzed. Sixty-three were in the CPAP group and 68 were in the usual care group, 41 had good adherence to CPAP (65.1%), and the median follow-up time was 43.0 (35.0, 54.0) months. In Cox regression analysis, ACE inhibitors and nitrates were independent factors for decreased survival in patients with comorbid OSA and CV/CeV (chi-square = 22.932, P = 0.003; ACE inhibitors: OR 7.241, P = 0.048, 95% CI 1.016-51.628; nitrates: OR 18.012, P = 0.011, 95% CI 1.923-168.750). ACE inhibitors increased mortality and secondary endpoints in the CPAP group (chi-square = 4.134, P = 0.042) but not in patients with good CPAP adherence. Clopidogrel and nitrates decreased survival in usual care group (clopidogrel: chi-square = 5.312, P = 0.021; nitrates: chi-square = 6.417, P = 0.011), but not in CPAP group. CONCLUSIONS: OSA may predispose patients with CV/CeV and CV/CeV medications to a negative effect. CPAP treatment may neutralize the negative effects of OSA by relieving chronic intermittent hypoxia. Trial registration ClinicalTrials.gov (NCT00738179, first registration date: 20/08/2008).

Extracellular vesicles derived from lung cancer cells exposed to intermittent hypoxia upregulate programmed death ligand 1 expression in macrophages.

PURPOSE: Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), compromises immune surveillance through the upregulation of programmed cell death-1 ligand (PD-L1). Tumor-released extracellular vesicles (EVs) have been reported to modulate immunosuppressive activities. We investigated whether or not EVs derived from intermittent hypoxic lung cancer cells can alter the expression of PD-L1 in macrophages. METHODS: The expression of PD-L1+monocytes from 40 patients with newly diagnosed non-small-cell lung cancer (NSCLC) and with (n=21) or without (n=19) OSA were detected. Plasma EVs isolated from NSCLC patients with moderate-severe OSA (n=4) and without OSA (n=4) were co-cultured with macrophages. A549 cells were exposed to normoxia or IH (48 cycles of 5 min of 1% O2 hypoxia, followed by 5 min of normoxia). EVs were isolated from cell supernatant and were co-cultured with macrophages differentiated from THP-1. PD-L1 and hypoxia-inducible factor-1 α (HIF-1α) expressions were measured by flow cytometry, immunofluorescence, and Western blot analysis. RESULTS: PD-L1+monocytes were elevated in NSCLC patients with OSA and increased with the severity of OSA and nocturnal desaturation. PD-L1+ macrophages were induced by EVs from NSCLC patients with OSA and positively correlated with HIF-1α expressions. EVs from IH-treated A549 can promote PD-L1 and HIF-1α expression in macrophages and the upregulation of PD-L1 expression was reversed by specific HIF-1α inhibitor. CONCLUSION: IH can enhance the function of EVs derived from lung cancer cells to aggravate immunosuppressive status in macrophages. HIF-1α may play an important role in this process.

Cerebral arterial air embolism after endobronchial electrocautery: a case report and review of the literature.

BACKGROUND: Endobronchial electrocautery is a common and safe therapeutic endoscopic treatment for malignant airway obstruction. Cerebral arterial air embolism (CAAE) is a rare but potentially fatal complication of endobronchial electrocautery. CASE PRESENTATION: We present the first case of cerebral arterial air embolism after endobronchial electrocautery. A 56-year-old male with a pulmonary tumour in the right upper lobe received repeated endobronchial electrocautery. During the procedure, he experienced unresponsiveness, hypoxemia and bradycardia, and he developed tetraplegia. Brain computed tomography showed several cerebral arterial air emboli with low-density spots in the right frontal lobe. He received hyperbaric oxygen therapy with almost full recovery, except for residual left-sided weakness. CONCLUSIONS: General physicians should realize that CAAE may be a possible complication of endobronchial electrocautery. Several measures, including avoiding positive pressure, lowering ventilatory pressures if possible, avoiding advancing the bronchoscope to occlude the bronchus and using the non-contact technique, should be used to prevent this devastating complication.

Effect of cigarette smoke extract on mitochondrial division in mouse quadriceps femoris cells.

BACKGROUND: To observe the effect of cigarette smoke extract (CSE) on mitochondrial division in mouse quadriceps femoris cells and to explore the potential molecular mechanism of skeletal muscle dysfunction (SMD) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Quadriceps femoris were cultured, passaged, and stimulated with different concentrations of CSE. We divided cells into four groups (Control, 2.5%, 5%, 10%). The growth of cells, the expression of Dynamin related protein 1 (Drp-1), and apoptosis were observed and evaluated by fluorescence microscopy, RT-PCR, Western blot, and flow cytometry. RESULTS: The longer the intervention time, the more obvious the decrease in cell number. In the 5% and 10% groups, the cells became round with gaps. Under an inverted fluorescence microscope, the green fluorescence of cells in 5% and 10% stained with Mito-Tracker Green was significantly less than that of the Control and 2.5%. Red fluorescence was reduced and the green fluorescence was increased in the 5% and 10% stained with JC-1. Flow cytometry analysis showed that reactive oxygen species (ROS) and apoptosis were increased in the CSE intervention groups. In the Control, 2.5%, 5%, and 10%, the levels of ROS were 0.052±0.015, 0.170±0.030, 5.340±0.500, and 24.400±1.900, respectively. The apoptotic rates (%) were 0.270±0.009, 2.650±0.060, 11.850±0.020, and 31.820±1.260, respectively. The relative expression levels were, 0.900±0.093, 1.141±0.099, 1.361±0.034, 2.155±0.092 for DNM1L mRNA, and 0.509±0.008, 0.569±0.028, 0.792±0.048, 0.940±0.062 for Drp-1. There were significant differences in the apoptotic rate, and Drp-1 expression between 5% and 10% compared with the Control and 2.5% (P<0.05). CONCLUSIONS: CSE may enhance mitochondrial division of quadriceps femoris cells by up-regulating the expression of Drp-1, affecting cellular energy metabolism and promoting quadriceps femoris apoptosis, ultimately leading to the occurrence and development of skeletal muscle dysfunction in COPD.

A nomogramic model based on clinical and laboratory parameters at admission for predicting the survival of COVID-19 patients.

BACKGROUND: COVID-19 has become a major global threat. The present study aimed to develop a nomogram model to predict the survival of COVID-19 patients based on their clinical and laboratory data at admission. METHODS: COVID-19 patients who were admitted at Hankou Hospital and Huoshenshan Hospital in Wuhan, China from January 12, 2020 to March 20, 2020, whose outcome during the hospitalization was known, were retrospectively reviewed. The categorical variables were compared using Pearson's χ2-test or Fisher's exact test, and continuous variables were analyzed using Student's t-test or Mann Whitney U-test, as appropriate. Then, variables with a P-value of ≤0.1 were included in the log-binomial model, and merely these independent risk factors were used to establish the nomogram model. The discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), and internally verified using the Bootstrap method. RESULTS: A total of 262 patients (134 surviving and 128 non-surviving patients) were included in the analysis. Seven variables, which included age (relative risk [RR]: 0.905, 95% confidence interval [CI]: 0.868-0.944; P < 0.001), chronic heart disease (CHD, RR: 0.045, 95% CI: 0.0097-0.205; P < 0.001, the percentage of lymphocytes (Lym%, RR: 1.125, 95% CI: 1.041-1.216; P = 0.0029), platelets (RR: 1.008, 95% CI: 1.003-1.012; P = 0.001), C-reaction protein (RR: 0.982, 95% CI: 0.973-0.991; P < 0.001), lactate dehydrogenase (LDH, RR: 0.993, 95% CI: 0.990-0.997; P < 0.001) and D-dimer (RR: 0.734, 95% CI: 0.617-0.879; P < 0.001), were identified as the independent risk factors. The nomogram model based on these factors exhibited a good discrimination, with an AUC of 0.948 (95% CI: 0.923-0.973). CONCLUSIONS: A nomogram based on age, CHD, Lym%, platelets, C-reaction protein, LDH and D-dimer was established to accurately predict the prognosis of COVID-19 patients. This can be used as an alerting tool for clinicians to take early intervention measures, when necessary.

Adverse reaction report and retrospective analysis of black hairy tongue caused by linezolid.

The adverse reaction of Black Hairy Tongue (BHT) caused by linezolid is rare. We reports a case of linezolid-induced BHT, and reviews relevant literatures at home and abroad. It aims to provide a safe and reasonable basis for clinical medication use. A 14-year-old adolescent with pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) developed a rash and pruritus due to Vancomycin. Instead, the patient was given linezolid 600mg q12h in injection during hospitalization and in tablet after discharge. On the 14th day after injection and the second day after oral administration the patient showed BHT without other abnormal taste symptoms. But all the symptoms could be tolerated and he completed the therapy course of linezolid. Tongue symptoms completely disappeared on the 8th day after drug withdrawal. Based on the Karch and Lasagna evaluation methods and the cause-and-effect evaluation methods of the WHO collaborating center for international adverse drug reaction (ADR) monitoring, it is likely that this patient had a BHT caused by linezolid. The mean time of occurrence of BHT was 14.36 days, and the mean time of symptom disappearance was 23.43 days after drug administration. When linezolid is prescribed to patients, especially those with atopy, the patient's tongue should be closely observed and good oral hygiene is recommended.

A study on infectivity of asymptomatic SARS-CoV-2 carriers.

BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.

Short-term prognostic effects of circulating regulatory T-Cell suppressive function and vascular endothelial growth factor level in patients with non-small cell lung cancer and obstructive sleep apnea.

OBJECTIVE: To determine if suppressive function of regulatory T-cells (Tregs) and vascular endothelial cell growth factor (VEGF) levels are closely associated with prognosis of patients with non-small cell lung cancer (NSCLC) and obstructive sleep apnea (OSA). METHODS: Peripheral blood from 20 OSA patients, 44 newly diagnosed NSCLC patients with (n = 22) and without (n = 22) OSA was collected. Forkhead box protien 3 plus (Foxp3+) and CTLA-4+ Tregs ratio were analyzed with flow cytometry. Levels of VEGF, IL-10 and TGF-ß1 were analyzed with enzyme-linked immuno sorbent assay. NSCLC patients with and without OSA were followed up for two years. Optimal cutoff values were determined by receiver operating characteristic curves. Survival analysis were performed using the Kaplan-Meier test. RESULTS: NSCLC patients with OSA showed higher Foxp3+Tregs ratio, higher plasma VEGF and TGF-ß1 levels when compared with NSCLC patients without OSA (P < 0.05). In NSCLC patients with OSA or not, subjects with higher Foxp3+Treg ratio, higher TGF-ß1 and VEGF levels tended to have poor mean survival time and two-year overall survival (OS, Foxp3+Treg: 636.7 vs. 704.8 days, 59.0% vs. 82.6%, P = 0.125; TGF-ß1: 637.8 vs. 698.4 days, 57.0% vs. 84.4%, P = 0.054; VEGF: 642.9 vs. 677.5 days, 48.6% vs. 81.3%, P = 0.074). Multivariate Cox regression adjusted for disease stage and receipt of systemic treatments, confirmed the links between high VEGF level and worse OS (HR: 1.003; 95% CI: 1.001-1.005; P = 0.021). CONCLUSIONS: OSA may up-regulate the expression of circulating TGF-ß1, VEGF and Foxp3+Tregs expression in NSCLC patients. Elevated VEGF level is closely associated with worse short-term survival in NSCLC patients with OSA or not.

MIP-T3 Expression Associated with Defects of Ciliogenesis in Airway of COPD Patients.

Introduction. Some studies have found that cilia were shorter in COPD smokers than in nonsmokers or healthy smokers. However, the structural abnormalities of cilia and the cause of such abnormalities in COPD patients still remain unknown. Tumor necrosis factor alpha receptor 3 interacting protein 1 (MIP-T3) may play an important role in the progress of ciliary protein transporting. Objectives: This study aimed at exploring the dominated structural abnormalities of cilia and the involvement of MIP-T3 in the pathogenesis of cilia of COPD patients. Methods: Patients who accepted pulmonary lobectomy were divided into 3 groups: the chronic obstructive pulmonary disease (COPD) smoker group, the healthy smoker group, and the nonsmoker group, according to smoking history and pulmonary function. The ultrastructure of cilia and the percentage of abnormal cilia were analyzed using a transmission electron microscope. Real-time PCR, immunohistochemical staining, and western blotting in bronchial epithelium were used to determine MIP-T3 mRNA and protein expression. The relationship between the percentage of abnormal cilia and lung function and MIP-T3 protein expression was analyzed. Results: Patients in the COPD smoker group had increased percentage of abnormal cilia comparing to both the healthy smoker group and the nonsmoker group (both P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (. Conclusions: Our results suggested that the abnormal ciliary ultrastructure, which was common in COPD patients, might be due to MIP-T3 downregulation.

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

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