[The performance of digital chest radiographs in the detection and diagnosis of pulmonary nodules and the consistency among readers].

Objective: To investigate the detection and diagnostic efficacy of chest radiographs for ≤30 mm pulmonary nodules and the factors affecting them, and to compare the level of consistency among readers. Methods: A total of 43 patients with asymptomatic pulmonary nodules who consulted in Cancer Hospital, Chinese Academy of Medical Sciences from 2012 to 2014 and had chest CT and X-ray chest radiographs during the same period were retrospectively selected, and one nodule ≤30 mm was visible on chest CT images in the whole group (total 43 nodules in the whole group). One senior radiologist with more than 20 years of experience in imaging diagnosis reviewed CT images and recording the size, morphology, location, and density of nodules was selected retrospectively. Six radiologists with different levels of experience (2 residents, 2 attending physicians and 2 associate chief physicians independently reviewed the chest images and recorded the time of review, nodule detection, and diagnostic opinion. The CT imaging characteristics of detected and undetected nodules on X images were compared, and the factors affecting the detection of nodules on X-ray images were analyzed. Detection sensitivity and diagnosis accuracy rate of 6 radiologists were calculated, and the level of consistency among them was compared to analyze the influence of radiologists' seniority and reading time on the diagnosis results. Results: The number of nodules detected by all 6 radiologists was 17, with a sensitivity of detection of 39.5%(17/43). The number of nodules detected by ≥5, ≥4, ≥3, ≥2, and ≥1 physicians was 20, 21, 23, 25, and 28 nodules, respectively, with detection sensitivities of 46.5%, 48.8%, 53.5%, 58.1%, and 65.1%, respectively. Reasons for false-negative result of detection on X-ray images included the size, location, density, and morphology of the nodule. The sensitivity of detecting ≤30 mm, ≤20 mm, ≤15 mm, and ≤10 mm nodules was 46.5%-58.1%, 45.9%-54.1%, 36.0%-44.0%, and 36.4% for the 6 radiologists, respectively; the diagnosis accuracy rate was 19.0%-85.0%, 16.7%-6.5%, 18.2%-80.0%, and 0%-75.0%, respectively. The consistency of nodule detection among 6 doctors was good (Kappa value: 0.629-0.907) and the consistency of diagnostic results among them was moderate or poor (Kappa value: 0.350-0.653). The higher the radiologist's seniority, the shorter the time required to read the images. The reading time and the seniority of the radiologists had no significant influence on the detection and diagnosis results (P>0.05). Conclusions: The ability of radiographs to detect lung nodules ≤30 mm is limited, and the ability to determine the nature of the nodules is not sufficient, and the increase in reading time and seniority of the radiologists will not improve the diagnostic accuracy. X-ray film exam alone is not suitable for lung cancer diagnosis.

[Prevalence and risk factors of coronary artery calcification on lung cancer screening with low-dose CT].

Objective: To investigate the prevalence and risk factors of coronary artery calcification (CAC) on lung cancer screening with low-dose computed tomography (LDCT). Methods: A total of 4 989 asymptomatic subjects (2 542 males and 2 447 females) who underwent LDCT lung cancer screening were recruited at Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2017. The visual scoring method was used to assess coronary artery calcification score. χ(2) test or independent t-test was used to compare the difference of CAC positive rate among different groups. Multivariate logistic regression was used to analyze risk factors associated with CAC in the study. Results: Of the 4 989 asymptomatic subjects, CAC occurred in 1 018 cases. The positive rate was 20.4%, of which mild, moderate and severe calcification accounted for 86.3%, 11.4% and 2.3%, respectively. Gender, age, BMI, education level, occupation, smoking history, diabetes, hypertension and hyperlipidemia had statistically significant differences in CAC positive rates among groups. Multivariate logistic regression analysis showed that gender, age, diabetes, hypertension, hyperlipidemia and smoking history were risk factors for CAC. Age, diabetes, hypertension and smoking history were statistically significant risk factors between the mild and moderate CAC group. A total of 1 730 coronary arteries in 1 018 CAC positive cases had calcification, CAC positive rate of left anterior descending was the highest(51.3%); 568 cases (55.8%) were single vessel calcification, 450 cases (44.2%) were multiple vessel calcification. Conclusions: LDCT can be used for the 'one-stop' early detection of lung cancer and coronary atherosclerosis. Gender, age, diabetes, hypertension, hyperlipidemia and smoking are related risk factors for coronary atherosclerosis.

[Establishment of morphological reference values for the differential count of white blood cells in peripheral blood smear, as well as nucleated cells and megakaryocytes in bone marrow smear].

Objective: To establish the morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear. Methods: From April 2012 to June 2020, 4 221 healthy donors for hematopoietic stem cell transplantation in Hebei Yanda Lu Daopei Hospital were selected. The median age was 36 (3-72) years old, including 2 520 males and 1 701 females. They were divided into four groups according to age: children group, with age≤14 years old [n=334, 11 (3-14) years old], youth group, with age >14 years old and <45 years old [n=2 855, 33 (15-44) years old], middle-aged adult group, with age ≥45 years old and < 60 years old [n=929, 49 (45-59) years old], and older adult group, with age ≥60 years old [n=103, 62 (60-72) years old]. Gender subgroups were established in each age group. According to different hematopoietic characteristics, the children group were divided into two subgroups: children group 1 [n=48, 6 (3-7) years old] and children group 2 [n=286, 11 (8-14) years old]. According to the clinical routine, 100 white blood cells in peripheral blood, 200 nucleated cells in bone marrow, and cell numbers/4.5 cm2 for megakaryocytes were classified and counted. The results of cell count in different age and gender groups were compared, and the reference values of morphological classification were established for different groups with statistical or clinical significance. Results: Due to the existence of statistically significant differences between children and adult groups and different gender subgroups in adults (all P<0.05), the reference values were established for children group and adult gender subgroups. The counts of segmented neutrophils and lymphocytes in peripheral blood were 46.65(43.97-49.32)% and 44.00(10.60-65.10)% in children group 1, 50.73(49.50-51.96)% and 39.55 (38.36-40.74)% in children group 2, and 57.00 (39.00-75.23) % and 33.00 (17.00-52.00) % in adult group, respectively. Bone marrow segmented neutrophils, orthochromatic erythroblasts, and mature lymphocytes were 11.54 (10.68-12.41)%, 14.20 (13.19-15.21)%, and 23.99 (22.06-25.92)% in children group 1, 12.50 (7.00-21.50)%, 15.00(9.50-25.50)%, and 21.02 (20.24-21.81)% in children group 2, 13.50 (7.50-21.00)%, 16.50 (10.50-26.00)%, and 15.50 (7.50-26.00)% in adult male group, and 14.50 (8.00-24.50)%, 14.50 (9.00-23.00)%, and 17.50 (8.50-29.00)% in adult female group, respectively. The myelopoiesis/erythropoiesis ratio in children group, adult male group and adult female group was 1.86∶1 (1.14∶1-3.23∶1), 1.96∶1 (1.12∶1-3.19∶1), 2.22∶1 (1.30∶1-3.69∶1), respectively. The numbers of granular megakaryocytes and thromocytogenic megakaryocytes were 138 (25-567) cells/4.5cm2 and 86 (13-328) cells/4.5 cm2 in children group, and 92 (13-338) cells/4.5 cm2 and 38 (3-162) cells/4.5 cm2 in adult group, respectively. Conclusion: The morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear are successfully established, which is helpful to improve the application of morphological examination in disease screening, diagnosis and monitoring.

[HRCT features differentiate synchronous multiple primary lung adenocarcinomas from intrapulmonary metastases].

Objective: To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. Methods: The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared. Results: The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group (P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different (P<0.05). Further analysis by multivariate logistic regression showed that the male (OR=5.742, P=0.010), SN (OR=41.291, P<0.01) and pleural attachment (OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN (P<0.01), showing round lesions with well-defined margin, attaching the pleura (P<0.05). Conclusions: The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.

[Clinical and immunological characteristics of a case with activated phosphoinositide 3-kinase δ syndrome 2].

Objective: To analyze the clinical and immunological characteristics of a patient with activated phosphoinositide 3-kinase δ syndrome 2 (APDS2). Methods: A retrospective analysis of clinical data, immune-related gene sequencing, imaging and laboratory findings of a patient with APDS2 admitted to Children's Hospital of Chongqing Medical University was performed. The absolute and relative numbers of peripheral lymphocyte subsets, immune cell subsets and phenotypes were detected by flow cytometry with the age matched healthy child or the patient's father as a control. Results: A female patient aged 6 years and 4 months old was firstly admitted due to paleness over one month and cough for 7 days in June 2017. The IgA (<0.067 g/L) decreased while the IgM (2.55 g/L) increased. The abdominal ultrasound found hepatomegaly (subcostal 1.7 cm) and splenomegaly (subcostal 3.6 cm), and gene sequencing revealed a heterozygous mutation in the PIK3R1 gene c.1425+1G>A. After the treatment with prednisone which was initiated with a dose of 10 mg/times, 3 times/d and continued and tapered over 7 months, the IgM decreased to normal (1.72 g/L), and the hepatomegaly (subcostal 0 cm) and splenomegaly (subcostal 0.5 cm) were improved. The patient was readmitted due to pale and sallow complexion for half a month in July 2019. The percentage of naive CD4(+)T (0.386) and naive CD8(+)T cells (0.271) were decreased while the percentage of terminally differentiated effector memory CD8(+)T cells (0.377) and transitional B cells (0.223) were increased. The mean fluorescence intensity (MFI) of phosphorylated protein kinase B (AKT) in CD3(+)T, CD4(+)T and CD8(+)T cells were higher in the patient (4 125, 5 213, 3 497) than those in her father (3 434, 3 312, 3 058). The percentage of follicular helper T cell (Tfh) (0.299), Th1 (0.491) and Th1-like cells (0.438) in the patient were higher than those in the healthy control (0.156,0.313,0.303), while the percentage of Th17 (0.126) and Th17-like cells (0.188) were lower than those in the healthy control (0.198, 0.315). And the percentage of CD57 in the patient (0.306) was also higher than that in the healthy control (0.246). Conclusions: The humoral immunity and cellular immunity of APDS2 patient are impaired to varying degrees. The steroid can improve the lymphoproliferation and autoimmune hemolytic anemia in this case.

LncRNA SNHG8 participates in the development of endometrial carcinoma through regulating c-MET expression by miR-152.

OBJECTIVE: To investigate the possible function and mechanism of lncRNA SNHG8 in the pathogenesis of endometrial carcinoma. PATIENTS AND METHODS: We utilized qRT-PCR to detect the expression of SNHG8 in 60 cases of endometrial carcinoma and 25 cases of normal endometrium; after that, the endometrial carcinoma cell lines were screened. SNHG8 was transfected into endometrial carcinoma cells by Lipofectamine and the proliferative activity of cells was detected by cell counting kit-8 (CCK-8) assay. Bioinformatics methods were used to detect the target microRNA. miR-152 is predicted to bind to SNHG8 and target genes of c-MET. Luciferase reporter assay was performed to detect the relative luciferase activity between miR-152 and c-MET, SNHG8. The interactions between SNHG8, miR-152, and c-MET were further verified by transfection of miR-152 mimics, miR-152 mimics + OE-SNHG8, SNHG8 siRNA, and SNHG8 siRNA + miR-152 inhibitor. RESULTS: SNHG8 expression in endometrial carcinoma tissue was significantly higher than that in normal endometrium. After transfection with SNHG8 siRNA, the cell viability of AN3CA cells decreased, whereas the activity of Ishikawa was increased after transfection with SNHG8 overexpression plasmid. Bioinformatics predictions and dual luciferase reporter assay illustrated that SNHG8 was bound to miR-152 and miR-152 targeted on c-MET. In addition, miR-152 mimics inhibited the expression of c-MET, and the inhibitory effect was reversed after SNHG8 overexpression. Silencing SNHG8 reduced c-MET expression, and c-MET expression was reversed after addition of miR-152 inhibitor. CONCLUSIONS: SNHG8 is highly expressed in endometrial carcinoma, and SNHG8 targets c-MET through miR-152 to regulate the proliferation of endometrial cancer cells.

KrasG12D-LOH promotes malignant biological behavior and energy metabolism of pancreatic ductal adenocarcinoma cells through the mTOR signaling pathway.

Oncogenic Kras with loss of heterozygosity (LOH) is frequently detected in various tumours. However, the exact function and mechanism by which KrasG12D-LOH operates remain unclear. Therefore, the current study investigated the effect of KrasG12D-LOH on the malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) cells. Our investigation revealed that KrasG12D-LOH is associated with increased proliferation, invasion and reduced apoptosis in PDAC cells. The results also exhibited enhanced glycolytic phenotype of KrasG12D-LOH PDAC cells. Hyperactive mTOR plays a significant role in the initiation and maintenance of tumors. To investigate the correlation between KrasG12D-LOH and mTOR, the mTOR signaling pathway was detected by western blot analysis. We found that KrasG12D-LOH up-regulated Akt, AMPK, REDD1 and mTOR in PDAC cells. In summary, our results demonstrated that KrasG12D-LOH promotes oncogenic Kras-induced PDAC by regulating energy metabolism and mTOR signaling pathway. These data may provide novel therapeutic perspectives for PDAC.

The morphological changes of bronchovascular bundles within subsolid nodules on HRCT correlate with the new IASLC classification of adenocarcinoma.

AIM: To observe the morphological changes of bronchovascular bundles within subsolid nodules on high-resolution (HR) computed tomography (CT) and analyse the correlation with the new adenocarcinoma classification. MATERIALS AND METHODS: Two hundred and sixteen lesions (absent consolidation on mediastinal window) were reviewed retrospectively. CT features including dimensions, contour, morphological changes of the blood vessels, and bronchi/bronchioles, vacuole signs, and their correlation with histopathology were evaluated. RESULTS: Excluding nine non-cancerous lesions, 34 pre-invasive lesions (PILs) including 15 atypical adenomatous hyperplasias (AAHs) and 19 adenocarcinomas in situ (AISs), 21 minimally invasive adenocarcinomas (MIAs), and 152 invasive adenocarcinomas (IACs) were analysed. Lepidic, acinar, and papillary patterns were identified in this cohort of adenocarcinomas. IACs were grouped into three types: type I (lepidic pattern ≥80%, n=47), type II (lepidic pattern ≥50%, <80%, n=67), and type III (lepidic pattern <50%, n=38). The contour of lesions, and morphological changes in vessels and bronchi/bronchioles significantly correlated with the classification of PIL, MIA, and IACs (p=0.000, p=0.000, and p=0.017, respectively). In IACs, the prevalence of vascular abnormalities on HRCT significantly correlated with (p=0.000) the proportion of non-lepidic pattern (23.40% in type I, 58.21% in type II, and 76.32% in type III); the prevalence of bronchial/bronchiolar abnormalities was higher (p=0.008) in type II/III (20.95%) compared with type I (6.38%). CONCLUSIONS: The morphological changes of vessels and bronchi/bronchioles within the subsolid nodules on HRCT help to differentiate IAC from PIL and MIA, and are more common in non-lepidic predominant adenocarcinomas.

Cervical necrotizing fasciitis due to methicillin-resistant Staphylococcus aureus: a case report.

Cervical necrotizing fasciitis is an uncommon but potentially fatal infection characterized by rapidly progressive, widespread necrosis of the superficial fascia. The authors report a case of cervical necrotizing fasciitis of odontogenic origin in a male with uncontrolled diabetes mellitus. An early diagnosis was based on clinical examination, confirmed by computed tomography (CT) scan, which showed multiple collections of air in the left submandibular, submental and cervical region. Broad spectrum antibiotic therapy was started quickly followed by surgical drainage and debridement. Pus culture was positive for methicillin-resistant Staphylococcus aureus. Four days after admission, mediastinitis was revealed by CT and drainage was conducted through a transcervical incision. The patient was treated successfully with antimicrobial therapy, repeated surgical debridement and supportive care.

Cervical infection with descending mediastinitis: a review of six cases.

The aim of this study was to retrospectively review cases of cervical infection with descending mediastinitis, and to analyse the clinical character, diagnosis and treatment of this infection. Six patients were identified from December 1998 to June 2005. Their aetiology, associated systemic diseases, bacteriology, radiology, treatments and outcomes were reviewed. Four cases resulted from odontogenic infection, one from upper airway infection, and one had an unknown cause. Diffuse swelling in face and neck, chest distress, tachypnea, and fever were the main symptoms. Chest radiography showed a widening of the upper mediastinal shadow in four patients. Four patients underwent computed tomographic scanning that confirmed the diagnosis of descending mediastinitis, which suggests that routine use of this scan be highly recommended for early detection. Six different pathogens were identified through pus and blood culture. All patients underwent surgical drainage. Three patients received a tracheotomy. Of the six patients, four achieved good results, and there were two deaths. Early surgical drainage remains the main treatment for cervical infection with descending mediastinitis. Delayed diagnosis, inadequate drainage and multidrug-resistant bacterial infection were responsible for the deaths.