Deep learning for malignancy risk estimation of incidental sub-centimeter pulmonary nodules on CT images.

OBJECTIVES: To establish deep learning models for malignancy risk estimation of sub-centimeter pulmonary nodules incidentally detected by chest CT and managed in clinical settings. MATERIALS AND METHODS: Four deep learning models were trained using CT images of sub-centimeter pulmonary nodules from West China Hospital, internally tested, and externally validated on three cohorts. The four models respectively learned 3D deep features from the baseline whole lung region, baseline image patch where the nodule located, baseline nodule box, and baseline plus follow-up nodule boxes. All regions of interest were automatically segmented except that the nodule boxes were additionally manually checked. The performance of models was compared with each other and that of three respiratory clinicians. RESULTS: There were 1822 nodules (981 malignant) in the training set, 806 (416 malignant) in the testing set, and 357 (253 malignant) totally in the external sets. The area under the curve (AUC) in the testing set was 0.754, 0.855, 0.928, and 0.942, respectively, for models derived from baseline whole lung, image patch, nodule box, and the baseline plus follow-up nodule boxes. When baseline models externally validated (follow-up images not available), the nodule-box model outperformed the other two with AUC being 0.808, 0.848, and 0.939 respectively in the three external datasets. The resident, junior, and senior clinicians achieved an accuracy of 67.0%, 82.5%, and 90.0%, respectively, in the testing set. The follow-up model performed comparably to the senior clinician. CONCLUSION: The deep learning algorithms solely mining nodule information can efficiently predict malignancy of incidental sub-centimeter pulmonary nodules. CLINICAL RELEVANCE STATEMENT: The established models may be valuable for supporting clinicians in routine clinical practice, potentially reducing the number of unnecessary examinations and also delays in diagnosis. KEY POINTS: • According to different regions of interest, four deep learning models were developed and compared to evaluate the malignancy of sub-centimeter pulmonary nodules by CT images. • The models derived from baseline nodule box or baseline plus follow-up nodule boxes demonstrated sufficient diagnostic accuracy (86.4% and 90.4% in the testing set), outperforming the respiratory resident (67.0%) and junior clinician (82.5%). • The proposed deep learning methods may aid clinicians in optimizing follow-up recommendations for sub-centimeter pulmonary nodules and may lead to fewer unnecessary diagnostic interventions.

Risk factors, outcomes, and epidemiological and etiological study of hospitalized COVID-19 patients with bacterial co-infection and secondary infections.

BACKGROUND: As a common complication of viral respiratory tract infection, bacterial infection was associated with higher mortality and morbidity. Determining the prevalence, culprit pathogens, outcomes, and risk factors of co-infection and secondary infection occurring in hospitalized patients with coronavirus disease 2019 (COVID-19) will be beneficial for better antibiotic management. METHODS: In this retrospective cohort research, we assessed clinical characteristics, laboratory parameters, microbiologic results, and outcomes of laboratory-confirmed COVID-19 patients with bacterial co-infection and secondary infection in West China Hospital from 2022 December 2nd to 2023 March 15th. RESULTS: The incidence of bacterial co-infection and secondary infection, as defined by positive culture results of clinical specimens, was 16.3% (178/1091) and 10.1% (110/1091) respectively among 1091 patients. Acinetobacter, Klebsiella, and Pseudomonas were the most commonly identified bacteria in respiratory tract samples of COVID-19 patients. In-hospital mortality of COVID-19 patients with co-infection (17.4% vs 9.5%, p = 0.003) and secondary infection (28.2% vs 9.5%, p < 0.001) greatly exceeded that of COVID-19 patients without bacterial infection. Cardiovascular disease (1.847 (1.202-2.837), p = 0.005), severe COVID-19 (1.694 (1.033-2.778), p = 0.037), and critical COVID-19 (2.220 (1.196-4.121), p = 0.012) were proved to be risk factors for bacterial co-infection, while only critical COVID-19 (1.847 (1.202-2.837), p = 0.005) was closely related to secondary infection. CONCLUSIONS: Bacterial co-infection and secondary infection could aggravate the disease severity and worsen clinical outcomes of COVID-19 patients. Notably, only critical COVID-19 subtype was proved to be an independent risk factor for both co-infection and secondary infection. Therefore, standard empirical antibiotics was recommended for critically ill COVID-19 rather than all the inpatients according to our research.

A training program for improving the capacity of infection high-throughput sequencing and diagnosis in China.

BACKGROUND: Infectious diseases are a serious threat to human especially since the COVID-19 outbreak has proved the importance and urgency of their diagnosis and treatment again. Metagenomic next-generation sequencing (mNGS) has been widely used and recognized in clinical and carried out localized testing in hospitals. Increasing the training of mNGS detection technicians can enhance their professional quality and more effectively realize the application value of the hospital platform. METHODS: Based on the initial theoretical understanding and practice of the mNGS platform for localization construction, we have designed a training program to enhance the ability of technicians to detect pathogens by utilizing mNGS, and hence to conduct training practices nationwide. RESULTS: Until August 30, 2022, the page views of online classes have reached 51,500 times and 6 of offline small-scale training courses have been conducted. A total of 67 trainees from 67 hospitals have participated in the training with a qualified rate of 100%. After the training course, the localization platform of 1 participating hospital has been put into use, 2 have added the mNGS localization platform for admission, among which 3 have expressed strong intention of localization. CONCLUSIONS: This study focuses on the training procedures and practical experience of the project which is the first systematic standardized program of mNGS in the world. It solves the training difficulties in the current industry, and effectively promotes the localization construction and application of mNGS in hospitals. It has great development potential in the future and is worth further promotion.

Performance of radiomics models derived from different CT reconstruction parameters for lung cancer risk prediction.

BACKGROUND: This study analysed the performance of radiomics features extracted from computed tomography (CT) images with different reconstruction parameters in differentiating malignant and benign pulmonary nodules. METHODS: We evaluated routine chest CT images acquired from 148 participants with pulmonary nodules, which were pathologically diagnosed during surgery in West China Hospital, including a 5 mm unenhanced lung window, a 5 mm unenhanced mediastinal window, a 5 mm contrast-enhanced mediastinal window and a 1 mm unenhanced lung window. The pulmonary nodules were segmented, and 1409 radiomics features were extracted for each window. Then, we created 15 cohorts consisting of single windows or multiple windows. Univariate correlation analysis and principal component analysis were performed to select the features, and logistic regression analysis was performed to establish models for each cohort. The area under the curve (AUC) was applied to compare model performance. RESULTS: There were 75 benign and 73 malignant pulmonary nodules, with mean diameters of 18.63 and 19.86 mm, respectively. For the single-window setting, the AUCs of the radiomics model from the 5 mm unenhanced lung window, 5 mm unenhanced mediastinal window, 5 mm contrast-enhanced mediastinal window and 1 mm unenhanced lung window were 0.771, 0.808, 0.750, and 0.771 in the training set and 0.711, 0.709, 0.684, and 0.674 in the test set, respectively. Regarding the multiple-window setting, the radiomics model based on all four windows showed an AUC of 0.825 in the training set and 0.743 in the test set. Statistically, the 15 models demonstrated comparable performances (P > 0.05). CONCLUSION: A single chest CT window was acceptable in predicting the malignancy of pulmonary nodules, and additional windows did not statistically improve the performance of the radiomics models. In addition, slice thickness and contrast enhancement did not affect the diagnostic performance.

The diagnostic and prognostic value of radiomics and deep learning technologies for patients with solid pulmonary nodules in chest CT images.

BACKGROUND: Solid pulmonary nodules are different from subsolid nodules and the diagnosis is much more challenging. We intended to evaluate the diagnostic and prognostic value of radiomics and deep learning technologies for solid pulmonary nodules. METHODS: Retrospectively enroll patients with pathologically-confirmed solid pulmonary nodules and collect clinical data. Obtain pre-treatment high-resolution thoracic CT and manually delineate the nodule in 3D. Then, all patients were randomly divided into training and testing sets at a ratio of 7:3, and convolutional neural networks (CNN) models and random forest (RF) models were established. Survival analyses were performed for patients with solid adenocarcinomas. RESULTS: Totally 720 solid pulmonary nodules were enrolled, 348 benign and 372 malignant. The CNN model with clinical features achieved the highest AUC [0.819, 95% confidence interval (CI): 0.760-0.877] with a sensitivity of 0.778, specificity of 0.788 and accuracy of 0.783. No significant differences were observed between the CNN and radiomics models. There were 295 solid adenocarcinomas in survival analysis. Different disease-free survival was observed between the low-risk and high-risk groups divided according to the radiomics Rad-score. However, the groups based on deep learning signatures showed similar survival. Cox regression analysis indicated that the radiomics Rad-score (hazard ratio: 5.08, 95% CI: 2.61-9.90) was an independent predictor of recurrence. CONCLUSIONS: The radiomics and deep learning models can well predict the malignancy of solid pulmonary nodules. Radiomics signatures also demonstrate prognostic value in solid adenocarcinomas.

Dasatinib-induced chylothorax: report of a case and review of the literature.

Dasatinib is a tyrosine kinase inhibitor for the treatment of BCR-ABL-positive chronic myeloid leukaemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL). Although fluid retention is a common adverse event associated with dasatinib, chylothorax is exceptionally rare. The pathological mechanism, clinical manifestation and management of dasatinib-induced chylothorax are completely unclear. A 71-year-old man treated with dasatinib for CML was admitted for progressive dyspnea. Computed tomography (CT) showed a pleural effusion that was more prominent on the right thoracic cavity. Thoracentesis showed thick milky pleural fluid, which was then confirmed as chylothorax by chylum qualitative tests and triglyceride measurements. Radionuclide lymphoscintigraphy yielded an obstruction at the end segment of the thoracic duct, but no leakage points were found. After excluding common causes, drug-induced chylothorax was presumed. Then, dasatinib was withdrawn, and 1 week later, chylothorax resolved. To further elucidate the relationship between the medication and chylothorax, dasatinib was resumed tentatively for 2 days. As expected, pleural effusion recurred soon. Based on these clinical manifestations, the diagnosis of dasatinib-induced chylothorax was identified. The patient was suggested to stop dasatinib and use an alternative drug as recommended by the haematologist. Pleural effusion is the common adverse reaction of dasatinib, but chylothorax is rare. Only six cases of dasatinib-induced chylothorax have been reported, and our patient is the seventh case. Once a patient with dasatinib treatment develops chylothorax, dasatinib should be considered one of the possible causes. If no other definitive aetiological factor is identified, dasatinib discontinuation might be the optimum scheme.

Primary pulmonary lymphoepithelioma-like carcinoma: a rare type of lung cancer with a favorable outcome in comparison to squamous carcinoma.

BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare tumor and often misdiagnosed as squamous carcinoma. In the current study, clinical characteristics and outcome of primary pulmonary LELC were systematically compared with pulmonary squamous carcinoma. METHODS: Forty-two cases of primary pulmonary LELC and 134 squamous carcinomas were enrolled retrospectively. Characteristic and prognosis difference between the two groups was compared, and the independent prognostic factor for pulmonary LELC was identified as well. RESULTS: In comparison to squamous carcinoma, pulmonary LELC was more common in women with a younger median age and less smokers. LELC seemed to be smaller in diameter on computed tomography (CT) scans than squamous carcinoma, with scarce spiculation and vascular convergence signs. Epstein-Bar virus-encoded RNA (EBER) by in-situ hybridization was detected in 33 LELC cases, among whom 27 ones were positive in serum EBV-DNA examination. LELC patients presented a much longer median progression-free survival (PFS) than squamous carcinoma. Positive serum EBV-DNA, distant lymph node invasion, advanced clinical stage and receiving radiotherapy were correlated with the shorter PFS in LELC patients. However, only positive serum EBV-DNA was the independent PFS predictor. CONCLUSION: Pulmonary LELC looks like distinct from squamous carcinoma. Middle-aged women and nonsmokers are comparatively predominated. CT features of pulmonary LELC are relatively less-malignant. Correspondently, the progression of pulmonary LELC is seemingly favorable than squamous carcinoma and the positive serum EBV-DNA appears to be the predictor of PFS.

A Higher Rate of Pulmonary Fungal Infection in Chronic Obstructive Pulmonary Disease Patients with Influenza in a Large Tertiary Hospital.

BACKGROUND: Influenza is considered a self-limiting disease. However, in patients with chronic obstructive pulmonary disease (COPD), it may result in serious outcomes during the flu season. OBJECTIVES: The aims of this retrospective study were to explore the characteristics of hospitalized patients with COPD complicated by influenza and determine the factors affecting the prognosis of these patients. METHOD: Demographic and clinical data were collected for 278 patients totally from the West China Hospital between January 1, 2016 and February 28, 2018. RESULTS: Among the patients with influenza, the positive fungal culture rate, and the rates of antifungal drug and systemic corticosteroids use were higher for those with COPD than for those without COPD. Respiratory failure was more common in patients with influenza and COPD than in patients with influenza only, while the proportion of severe cases was higher among the former than among the latter. Among the patients with COPD, the positive fungal culture rate, particularly for Aspergillus, and the rate of systemic corticosteroids use were higher for those with influenza than for those without influenza. Multivariate analysis revealed that a COPD history of >20 years and smoking for >20 pack-years were independent factors for susceptibility of COPD patients to influenza. CONCLUSIONS: Aspergillus infection seems to be more common in patients with influenza and COPD. In addition, COPD complicated by influenza during the seasonal outbreak can easily progress to a severe disease state. Heavy smokers and patients with a prolonged COPD history are more likely to be infected by influenza.

Supermacrocyclic Assemblies by Hydrogen-Bond Codes of C7-Phenol Pyrazolo and Pyrrolo Derivatives of Adenine.

Hydrogen bond (HB) mediated base pair motifs are versatile scaffolds of diverse supramolecular constructs. Here, we report that two new four- and six-membered supermacrocyclic assemblies with intriguing geometries could self-assemble from two new adenine derivatives, APN (1) and APC (2). The conversion of a conventional HB acceptor, N8 of 1, to a non-conventional HB donor, C8-H of 2, had a pronounced impact on the overall intricate HB network and self-assembly patterns, epitomizing the subtleties in design and exploitation of such base-pair motifs as promising tectons for building supramolecular architectures.

[Construction of sh-rpS6 lentivirus vectors and its effect on proliferation in lung adenocarcinoma A549 cell lines].

OBJECTIVE: To construct the sh-rpS6 lentivirus vector targeting ribosomal protein S6 (rpS6) and explore its effect on proliferation in lung adenocarcinoma A549 cell lines. METHODS: Sequences targeting the rpS6 gene were selected. The double strand shRNA oligo was ligated to pGCsil-GFP lentivirus vector and transformed into E. coli. The resulting recombinant vector was verified by sequencing. After transfection and lentivirus packing, the viral particles were collected and infected A549 cells. After selection of GFP positive cells by FACS, mRNA and protein expression levels of rpS6 were determined by real time PCR and Western blot. In the following experiment, the proliferation changes of A549 cell lines after the interference by sh-rpS6 was investigated by using CCK-8 kit. RESULTS: The sequencing result confirmed that pGCsil-sh-rpS6-GFP vector was successfully developed. Stably transfected A549 cell lines by sh-rpS6 were selected through FACS, with a selection ratio of 86.80%. The silencing effects of sh-rpS6 were determined by real time PCR and Western blot, suggesting that mRNA and protein expression of rpS6 in the targeted cells reduced by (79.72 +/- 6.83) % and (83.77 +/- 12.13) %, significantly lower than those of control groups. In vitro showed the cell proliferation with sh-rpS6 was significantly slower than that of controls (P < 0.05). CONCLUSION: The constructed sh-rpS6 lentivirus vector could inhibit the expression of rpS6 in A549 cell lines effectively and significantly slow the cell proliferation in vitro.

[Construction and expression of recombinant lentiviral vectors of AKT2,PDK1 and BAD].

OBJECTIVE: To construct human protein kinase B (ATK2), phosphoinositide-dependent kinase 1 (PDK1) and bcl-2-associated death protein (BAD) lentiviral expression vector, and to determine their expressions in 293T cells. METHODS: Total RNA was extracted from lung cancer tissues. The full-length coding regions of human ATK2, BAD and PDK1 cDNA were amplified via RT-PCR using specific primers, subcloned into PGEM-Teasy and then sequenced for confirmation. The full-length coding sequence was cut out with a specific restriction enzyme digest and subclone into pCDF1-MCS2-EF1-copGFP. The plasmids were transfected into 293T cells using the calcium phosphate method. The over expression of AKT2, BAD and PDK1 were detected by Western blot. RESULTS: AKT2, PDK1 and BAD were subcloned into pCDF1-MCS2-EF1-copGFP, with an efficiency of transfection of 100%, 95%, and 90% respectively. The virus titers were 6.7 x 10(6) PFU/mL in the supernatant. After infection, the proteins of AKT2, PDK1 and BAD were detected by Western blot. CONCLUSION: The lentivial vector pCDF1-MCS2-EF1-copGFP containing AKT2, BAD and PDK1 were successfully constructed and expressed in 293T cells.

The first reported pulmonary nocardiosis caused by Nocardia gipuzkoensis resisted to trimethoprim/sulfamethoxazol (TMP-SMZ) in an immunocompetent patient.

OBJECTIVES: Nocardia gipuzkoensis was first described as a novel and distinct species in 2020 by Imen Nouioui and pulmonary nocardiosis associated with N. gipuzkoensis was once reported in two bronchiectasis patients. Noteworthy, both reported N. gipuzkoensis cases showed sensitivity to trimethoprim/sulfamethoxazol (TMP-SMZ), which are usually recommended for empirical therapy. METHODS: We reported the third case of N. gipuzkoensis infection in a 16-year-old girl with chief complaints of cough and persistent chest and back pain. No underlying immuno-suppressive conditions and glucocorticoid use was revealed. Patchy lesions next to the spine and located in the posterior basal segment of the lower lobes of the left lung were seen in thorax computed tomography (CT), but no pathogenic bacteria were detected according to routine laboratory testings. RESULTS: Metagenomic next-generation sequencing (mNGS) combined with whole-genome sequencing (WGS) was used to classified our isolate from bronchoalveolar lavage fluid (BALF) as N. gipuzkoensis. It is worth mentioning that drug susceptibility testing of our isolate showed resistance to TMP-SMZ, which was never reported before. The patient improved remarkably both clinically and radiographically according to the treatment with imipenem-cilastatin infusion alone. CONCLUSION: mNGS and WGS showed excellent performance in identifying the Nocardia genus to the species level and improving the detection rate of N. gipuzkoensis ignored by traditional culture. Different from previously reported cases, the N. gipuzkoensis infection case showed resistance to TMP-SMZ, which is an unprecedented finding and a crucial addition to our understanding of the antibacterial spectrum of N. gipuzkoensis. The successful treatment with imipenem-cilastatin infusion alone in this case is a testament to the importance of precise identification and tailored antibiotic therapy.

The Impact of Early Antibiotic Use on Clinical Outcomes of Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis.

Purpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown. Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness. Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246-4.060), p = 1.000) and ICU admission (HR=0.436(0.093-2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296-1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221-8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort. Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.

Single-cell transcriptome analysis deciphers the CD74-mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune-inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single-cell level. METHODS: We performed single-cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co-culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single-cell analyses. RESULTS: LSCC with COPD showed increased proportions of tumour-associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. CONCLUSIONS: Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. HIGHLIGHT: Our results demonstrated higher proportions of tumour-associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-PD-L1 signalling pathway, facilitating immune evasion.

BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer.

BACKGROUND: The pro-apoptotic Bcl-2 protein BAD initiated apoptosis in human cells and has been identified as a prognostic marker in non-small cell lung cancer (NSCLC). In this study, we aimed to explore the functions of BAD in NSCLC. METHODS: Overexpression of BAD was performed by transfecting different NSCLC cell lines with wild-type BAD. Cell proliferation, cell cycle, apoptosis, and invasion were characterized in vitro. Tumorigenicity was analyzed in vivo. Western blot was performed to determine the effects of BAD overexpression on the Bcl-2 family proteins and apoptosis-related proteins. RESULTS: Overexpression of BAD significantly inhibited cell proliferation in H1299, H292, and SPC-A1 but not in SK-MES-1 and H460 cell lines in vitro. BAD overexpression also reduced the tumorigenicity of H1299/SPC-A1 cell in vivo. However, no appreciable effects on cell cycle distribution and invasion were observed in all these cell lines. BAD overexpression also induced apoptosis in all cell types, in which process expression of mitochondrial cytochrom c (cyto-c) and caspase 3 were increased, whereas Bcl-xl, Bcl-2, Bax and caspase 8 expressions did not changed. These findings indicated that a mitochondrial pathway, in which process cyto-c was released from mitochondrial to activate caspase 3, was involved in BAD overexpression-mediated apoptosis. CONCLUSIONS: Our data suggested that increased expression of BAD enhance apoptosis and has negative influence on cell proliferation and tumor growth in NSCLC. Bad is a new potential target for tumor interventions.

Pulmonary sclerosing hemangioma: a unique epithelial neoplasm of the lung (report of 26 cases).

BACKGROUND: Pulmonary sclerosing hemangioma (SH) is an uncommon tumor. The aim of this study was to identify the origin of pulmonary SH and summarize its clinicopathologic features. METHODS: Data of 26 cases of pulmonary SH were collected and reviewed, including their clinical symptoms, chest radiological examinations, treatments, and pathological findings. RESULTS: Female patients of pulmonary SH were markedly frequent (n=23, 88.46%). Solitary mass or nodule in the lung fields was the most common manifestation (n=24, 92.31%), especially in the right middle lobe (n=9, 34.62%). There were two kinds of tumor cells: lining cells and round cells. All tumors contained a mixture of papillary, solid, sclerotic, and hemorrhagic patterns. Immunohistochemistry with a variable number of antibodies was performed for some cases. All of the detected specimens revealed strong reaction of lining cells with epithelial markers, such as thyroid transcription factor-1 (TTF-1), epithelial membrane antigen (EMA), cytokeratin (CK), pancytokeratin (PCK), and cytokeratin 7 (CK-7), while round cells were positive with TTF-1 and EMA. Until the end of last contact, none of the patients died or suffered from the recurrence of the disease after surgical treatment. CONCLUSIONS: Pulmonary SH is a unique neoplasm of the lung with a characteristic solitary mass or nodule. Pulmonary epithelium might be the primary origin of the tumor cells.

Early lung cancer detection using the self-evaluation scoring questionnaire and chest digital radiography: a 3-year follow-up study in China.

The standard definition of high-risk individuals for lung cancer was not uniform and the value of chest digital radiography (DR) in lung cancer screening was still unproven. The aim of this study was to assess whether the original questionnaire named as "Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer" combined with DR examinations could detect early stage of lung cancer effectively. The Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer had been designed in previous studies. Subjects with scores over 116 points were regarded as high-risk individuals and underwent the current DR scans at least once a year from 2007 to 2009. Noncalcified nodules with a diameter over 30 mm, along with enlarged pulmonary hilus and atelectasis, were considered to be positive and subjected to further special examinations. Efficacy of the scoring questionnaire combined with DR scans was estimated by 3-year results. Among 1,537 subjects, 13, 11, and 7 were diagnosed with lung cancer in the first, second, and third year, respectively, indicating the detection rate of 2.02 % (31/1,537). In addition, 77.42 % (24/31) of the patients were in stage I and 51.61 % (16/31) were adenocarcinomas. For the 31 cases, 28 were defined as detected cancers, while the other three were interval ones, only accounting for 0.20 % (3/1,504) of individuals with negative judgments. The protocol of Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer combined with DR scans is a cost-effective and safe approach to detect early stage of lung cancer.

Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection.

Background and objectives: Disease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms. Methods: COVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers. Results: The oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway. Conclusion: The oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19.

Prognostic impact of Raf-1 and p-Raf-1 expressions for poor survival rate in non-small cell lung cancer.

Overexpression of Raf-1 has commonly been observed in solid tumors including non-small cell lung cancer (NSCLC). The objective of this study was to investigate whether overexpression of Raf-1, phosphorylated-Raf-1 (p-Raf-1) or both correlates with poor survival rate in NSCLC patients and to explore associations between expression of these proteins and NSCLC cell fate both in vitro and in vivo. Expression of Raf-1 and p-Raf-1 were detected by immunohistochemistry in tumor specimens from 152 NSCLC patients and associations between their expression and the clinicopathological characteristics were assessed. Five-year median survival rate of patients were analyzed by Kaplan-Meier method, log-rank test and Cox regression. Cell fate was compared between normal tumor cells and those with Raf-1 silencing, in both the adenocarcinoma cell line A549 and xenografted mice that were infected with the A549 cell line. The incidence of overexpression of both Raf-1 and p-Raf-1 in NSCLC was much higher than normal control (P < 0.05), and the survival rate of patients with positive expression of Raf-1, p-Raf-1 or both was found to be significantly lower than the negative group (P < 0.05). Both univariate and multivariate analyses showed Raf-1 (P = 0.000, P = 0.010), p-Raf-1 (P = 0.004, P = 0.046), or both (P = 0.001, P = 0.016) was good prognostic markers for poor survival rate in NSCLC patients. Suppression of Raf-1 inhibited tumorigenesis by inducing apoptosis both in vitro and in vivo. These findings demonstrate that overexpression of Raf-1, p-Raf-1 or both could be considered as a new independent prognostic biomarker for poor survival rates for NSCLC patients.