[Advances in the use of bevacizumab for the treatment of respiratory papilloma].

Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.

[HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases].

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

[Methylophiopogonanone a Inhibits LPS/ATP-Induced Macrophage Pyroptosis via ROS/NLRP3 Pathway].

As a byproduct of mitochondrial respiration or metabolism, reactive oxygen species (ROS) can act as a signaling molecule to activate NLR family pyrin domain containing 3 (NLRP3) inflammasome, thereby triggering immune response. NLRP3 inflammasome acts as a sensor of various danger signals and is central to the control of pyroptosis occurrence. Macrophage pyroptosis is closely related to atherosclerosis, arthritis, pulmonary fibrosis and other inflammatory diseases. Methylophiopogonanone A (MO-A) is a main homoisoflavonoid in Chinese herb Ophiopogonis Radix, which has antioxidant effect. However, it is not clear whether MO-A can alleviate macrophage pyroptosis by inhibiting oxidative stress. Here we have shown that MO-A increases the activities of superoxide dismutase (SOD) and catalase (CAT), inhibits the production of ROS, reduces the activation of NLRP3 inflammasome and the release of lactate dehydrogenase (LDH), and inhibits pyroptosis in macrophages induced by lipopolysaccharides (LPS) and adenosine triphosphate (ATP). These effects can be reversed by the ROS promoter H2O2. Therefore, MO-A can inhibit macrophage pyroptosis through the ROS/NLRP3 pathway and may be considered as a candidate drug for the treatment of inflammatory diseases.

[Preclinical study of T cell receptor specifically reactive with KRAS G12V mutation in the treatment of malignant tumors].

OBJECTIVE: KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability. METHODS: In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5' rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We obtained a high-affinity TCR sequence that specifically recognized the HLA-A*11:01-restricted KRAS G12V8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability. CONCLUSION: KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.

A preliminary study on colour Doppler ultrasound for the evaluation of intervertebral stenosis of the vertebral artery.

AIM: To determine the optimal thresholds for assessing intervertebral segment stenosis through haemodynamic parameters of colour Doppler ultrasound compared with computed tomography (CT) angiography. MATERIALS AND METHODS: Fifty-four patients diagnosed with intervertebral stenosis on colour Doppler imaging were included. Twenty patients with normal vertebral arteries constituted a control group. Peak systolic velocity at the intervertebral stenosis (PSVIV-S) and the intervertebral segment distal to the stenosis (PSVIV-D), end diastolic velocity at the intervertebral stenosis (EDVIV-S), and the intervertebral segment distal to the stenosis (EDVIV-D) were measured, and the ratios of PSVIV-S/PSVIV-D and EDVIV-S/EDVIV-D were calculated. Cut-off values for the diagnosis of <50%, 50-69%, and 70-99% stenosis were determined using a receiver operating characteristics curve. RESULTS: The optimal cut-off values of haemodynamic parameters for evaluating the intervertebral artery for <50% stenosis were PSVIV-S ≥81.5 cm/s, EDVIV-S ≥24.5 cm/s, PSVIV-S/PSVIV-D ≥1.49, and EDVIV-S/EDVIV-D ≥1.28; for 50-69% stenosis were PSVIV-S ≥137.5 cm/s, EDVIV-S ≥36.5 cm/s, PSVIV-S/PSVIV-D ≥3.14, and EDVIV-S/EDVIV-D ≥2.75; and for 70-99% stenosis were PSVIV-S ≥216 cm/s, EDVIV-S ≥55 cm/s, PSVIV-S/PSVIV-D ≥4.31, and EDVIV-S/EDVIV-D ≥4.16. PSVIV-S/PSVIV-D was the most superior haemodynamic parameter, with areas under the curve of 1.000, 0.906, and 0.968 for the diagnosis of <50%, 50-69%, and 70-99% stenosis, respectively. CONCLUSION: Colour Doppler sonography reliably identifies intervertebral stenosis. The results can be used as a preliminary reference for evaluating intervertebral stenosis.

Comparative analysis and differentiation between SAPHO syndrome and spondyloarthropathies using whole-spine MRI.

AIM: To determine the imaging characteristics of SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome and seronegative spondyloarthropathies (SpAs) on whole-spine magnetic resonance imaging (WS-MRI) and evaluate the role of WS-MRI in the diagnosis and differentiation of the two diseases. MATERIALS AND METHODS: Twenty-eight patients with SAPHO and 44 with SpAs were included. All patients were symptomatic and clinically diagnosed with SAPHO or SpAs, and all underwent WS-MRI for comparison of imaging characteristics. RESULTS: The mean age of the SAPHO patients was 48.7 ± 12.7 years, while that of the SpA patients was 34.7 ± 12.3 years (p<0.001). WS-MRI showed that the frequency of cervical, thoracic, and lumbar spine involvement was 53.6% versus 52.3%, 75% versus 88.6%, and 60.7% versus 63.6%, respectively (p=0.70, 0.13, and 0.80). The frequency of sacroiliac joint involvement was 7.1% and 100% (p<0.001). Continuous spinal involvement accounted for 50% versus 43.2%, 60.7% versus 84.1%, and 39.3% versus 40.9% in the cervical, thoracic, and lumbar vertebrae, respectively (p=0.03). WS-MRI showed that bone marrow oedema of spinal anterior corner was observed in 50% versus 75% (p=0.03). Vertebral body and posterior attachment involvement accounted for 85.7% versus 93.2% and 14.3% versus 34.1% (p=0.3, 0.06). The frequency of bone erosion in mobile spine was 75% and 36.4%, respectively (p=0.02). The frequency of intervertebral disc, endplate, anterior thoracic wall, and paraspinal soft-tissue swelling was 42.9% versus 18.2%, 53.6% versus 22.7%, 85.7% versus 42.2%, and 50% versus 11.4% (p=0.02, 0.00). CONCLUSIONS: Factors differentiating the two groups at WS-MRI were bone marrow oedema of the spinal anterior corner, bone erosion, and swelling of the intervertebral disc, endplate, anterior thoracic wall, and paraspinal soft-tissue.

Artemisia ordosica Polysaccharide Alleviated Lipopolysaccharide-induced Oxidative Stress of Broilers via Nrf2/Keap1 and TLR4/NF-κB Pathway.

Artemisia ordosica is one of the main shrubby perennials belonging to Artemisia species of Asteraceae and could be used in folk Chinese/Mongolian medicine to treat symptoms of various inflammatory ailments. The present study was conducted to investigate the protective effects of dietary Artemisia ordosica polysaccharide (AOP) against lipopolysaccharide (LPS) induced oxidative stress in broilers via Nrf2/Keap1 and TLR4/NF-κB pathway. A total of 192 1-day-old Arbor Acres male broilers were randomly allotted to four treatments with 6 replicates (n = 8): (1) CON group, non-challenged broilers fed basal diet; (2) LPS group, LPS-challenged broilers fed basal diet; (3) AOP group, non-challenged broilers fed basal diet supplemented with 750 mg/kg AOP; (4) LPS+AOP group, LPS-challenged broilers fed basal diet supplemented with 750 mg/kg AOP. The trial included starter phase (d 1-14), stress period Ⅰ (d 15-21), convalescence Ⅰ (d 22-28), stress period Ⅱ (d 29-35) and convalescence Ⅱ (d 36-42). During stress period Ⅰ (on d 15, 17, 19 and 21) and stress period Ⅱ (on d 29, 31, 33 and 35), broilers were injected intra-abdominally either with LPS solution or with an equal amount of sterile saline. The results showed that dietary AOP supplementation alleviated LPS-induced reduction in antioxidant enzyme activity and excessive production of ROS, 8-OHdG and PC in serum of broilers challenged with LPS. Moreover, dietary AOP supplementation alleviated the decrease of T-AOC and activities of SOD, CAT and GPx in liver of broilers challenged with LPS by increasing expression of Nrf2, and inhibiting over-expression of Keap1 both at gene and protein level. Additionally, dietary AOP supplementation decreased the over-production of IL-1ß and IL-6 in liver of broilers challenged by LPS through decreasing mRNA expression of TLR4, MyD88, NF-κB P65, IL-1ß and IL-6, and alleviating the increase of protein expression of TLR4, IKKß, NF-κB P65, IL-1ß, IL-6, and the decrease of protein expression of IkBα. In conclusion, dietary AOP supplementation could alleviate LPS-induced oxidative stress through Nrf2/Keap1 and TLR4/NF-κB pathway.

[Feasibility multi-center study of artificial intelligence assistance in cervical fluid-based cytology diagnosis].

Objective: To propose a method of cervical cytology screening based on deep convolutional neural network and compare it with the diagnosis of cytologists. Method: The deep segmentation network was used to extract 618 333 regions of interest (ROI) from 5, 516 cytological pathological images. Combined with the experience of physicians, the deep classification network with the ability to analyze ROI was trained. The classification results were used to construct features, and the decision model was used to complete the classification of cytopathological images. Results: The sensitivity and specificity were 89.72%, 58.48%, 33.95% and 95.94% respectively. Among the smears derived from four different preparation methods, this algorithm had the best effect on natural fallout with a sensitivity of 91.10%, specificity of 69.32%, positive predictive rate of 41.41%, and negative predictive rate of 97.03%. Conclusion: Deep convolutional neural network image recognition technology can be applied to cervical cytology screening.

Using deep-learning algorithms to classify fetal brain ultrasound images as normal or abnormal.

OBJECTIVES: To evaluate the feasibility of using deep-learning algorithms to classify as normal or abnormal sonographic images of the fetal brain obtained in standard axial planes. METHODS: We included in the study images retrieved from a large hospital database from 10 251 normal and 2529 abnormal pregnancies. Abnormal cases were confirmed by neonatal ultrasound, follow-up examination or autopsy. After a series of pretraining data processing steps, 15 372 normal and 14 047 abnormal fetal brain images in standard axial planes were obtained. These were divided into training and test datasets (at case level rather than image level), at a ratio of approximately 8:2. The training data were used to train the algorithms for three purposes: performance of image segmentation along the fetal skull, classification of the image as normal or abnormal and localization of the lesion. The accuracy was then tested on the test datasets, with performance of segmentation being assessed using precision, recall and Dice's coefficient (DICE), calculated to measure the extent of overlap between human-labeled and machine-segmented regions. We assessed classification accuracy by calculating the sensitivity and specificity for abnormal images. Additionally, for 2491 abnormal images, we determined how well each lesion had been localized by overlaying heat maps created by an algorithm on the segmented ultrasound images; an expert judged these in terms of how satisfactory was the lesion localization by the algorithm, classifying this as having been done precisely, closely or irrelevantly. RESULTS: Segmentation precision, recall and DICE were 97.9%, 90.9% and 94.1%, respectively. For classification, the overall accuracy was 96.3%. The sensitivity and specificity for identification of abnormal images were 96.9% and 95.9%, respectively, and the area under the receiver-operating-characteristics curve was 0.989 (95% CI, 0.986-0.991). The algorithms located lesions precisely in 61.6% (1535/2491) of the abnormal images, closely in 24.6% (614/2491) and irrelevantly in 13.7% (342/2491). CONCLUSIONS: Deep-learning algorithms can be trained for segmentation and classification of normal and abnormal fetal brain ultrasound images in standard axial planes and can provide heat maps for lesion localization. This study lays the foundation for further research on the differential diagnosis of fetal intracranial abnormalities. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

[Comparison of clinical and immunological features between clinically amyopathic dermatomyositis and typical dermatomyositis].

OBJECTIVE: To study the differences between clinically amyopathic dermatomyositis (CADM) and typical dermatomyositis (DM) on clinical and immunological features. METHODS: By collecting clinical data of 106 CADM patients and 158 DM patients from January 2010 to June 2019 in the department of Rheumatology and Immunology, Peking University People's Hospital, the clinical characteristics and immunological features in the two groups were compared, and the distribution characters and the clinical meanings of myositis autoantibodies were discussed in the two groups respectively. Myositis autoantibodies were measured by immunoblotting according to the manufacturers' instructions. RESULTS: In the aspects of clinical manifestations, CADM presented more with onset of interstial lung diseases (ILD) compared with DM (20.7% vs. 7.6%, P=0.002), and CADM-ILD was more likely to be acute ILD (58.3% vs. 26%, P < 0.001), and there were no differences between CADM and DM in cutaneous manifestations, accompanied with connective tissue disease (CTD) and malignancy. In CADM, the positive rate of rheumatoid factors and antinuclear antibodies was lower in DM. The most common myositis specific autoantibodies (MSAs) in CADM were anti-MDA5 (36%), anti-PL-7 (11.2%) and anti-TIF-1γ (10.1%). The most common MSAs in DM were anti-Jo-1 (19.2%), anti-TIF-1γ (11.5%) and anti-MDA5 (11.5%). Anti-MDA5 was correlated with acute ILD and skin ulceration both in CADM and DM; in CADM, skin ulceration was not associated with the titer of anti-MDA5; while in DM, skin ulceration was associated with high titer of anti-MDA5. In DM, anti-TIF-1γ was correlated with heliotrope eruption, V/shawl neck sign, perionychia erythma and malignancy, and higher rate of malignancy was seen in all titers of the anti-TIF-1γ positive patients. In CADM, anti-TIF1-γ showed no correlation with clinical manifestations. The most common myositis associated autoantibody was anti-Ro-52 both in CADM and DM. In CADM, anti-Ro-52 was associated with Raynaud's phenomenon and chronic ILD, while in DM, anti-Ro-52 was associated with mechanic's hands, noninfectious fever and accompanied CTD. CONCLUSION: Compared with DM, ILD is more likely to be acute in CADM. It is different between CADM and DM about the distribution of myositis autoantibodies and the clinical significance of the same myositis antibody, and the clinical significance of some myositis antibodies is related to titers.

[Evaluation of the efficacy of Chinese Children's Asthma Action Plan on the long-term management of children with asthma at home].

Objective: During the COVID-19 pandemic, the electronic "questionnaire star" was employed to investigate the general situation, medication situation and pandemic impact of children diagnosed with asthma in our hospital and enrolled in the electronic platform of the Chinese Children's Asthma Action Plan (CCAAP). The internet technology and big data were used to grasp the trend and asthma control of children who had been at home for a long time due to the pandemic, so as to facilitate the management. Methods: By random cluster sampling survey method, according to the needs and medication adherence score, the electronic "questionnaire star" was designed to conduct a survey among children (0 to 14 years old) who diagnosed with asthma and joined the CCAAP on the basis of bronchial asthma medication adherence scale. Finally, the results of electronic questionnaire survey were analyzed. Results: A total of 423 questionnaires were sent out, 422 of which were valid, with an effective response rate of 99.7%. The results of questionnaire survey showed that 296 cases were male, accounting for 70.1%, and 126 cases were female, accounting for 29.9%, with an average age of (5.4±2.6) years old. The average age of males and females was (5.3±2.6) and (5.4±2.6) years old, respectively. There were more children aged ≥5 years than children who were younger than 5 years. Additionally, 13.95% of the parents thought that the pandemic had more than moderate impact on children with asthma, and 76.12% of the children were in the green zone and had no asthma attack. The proportion of green zone inhaled drugs (79.8%) was higher than yellow zone and red zone (49.8%). After using the CCAAP platform, the dissatisfaction rate was only 1.42%. Moreover, 71.87% of the children's medical expenses decreased, and the proportion of frequent use and intermittent use of antibiotics reduced, however, the proportion of occasional use and never use of antibiotics increased significantly (all P<0.05). The average score of drug compliance was 4.56, and the more frequently the platform was used, the higher the score of medication compliance was (P<0.05). Conclusions: After using CCAAP management with the aid of internet technology, children with asthma who had been isolated at home for a long time were less affected by COVID-19, with high medication compliance, generally lower medical expenses, significantly reduced use of antibiotics, and high satisfaction. This management mode provides a new idea for internet medicine.

[Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors].

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

[Clinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation].

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION: EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.

[Clinicopathological features of ovarian Brenner tumors].

Objective: To investigate the clinicopathological characteristics and diagnosis of ovarian Brenner tumors. Methods: Forty-seven cases of ovarian Brenner tumors were enrolled from January 2012 to May 2018 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Clinical data, imaging examination, histopathological characteristics and immunohistochemical phenotype were analyzed. Results: The age of the patients ranged from 30-73 years and the mean age was 55 years. Thirty-nine patients (83.0%) were postmenopausal. Forty cases (85.1%) of the Brenner tumors were benign, five (10.6%) borderline and two (4.3%) malignant. Usual tumor markers of ovarian carcinoma, including CA199 and CA125 were normal or mild elevated in the 47 cases. Imaging before surgery was not specific to Brenner tumors. Microscopically, benign Brenner tumors were composed of nests of bland, transitional-type cells within a fibromatous stroma. In our 5 cases of borderline Brenner tumors, mildly atypical transitional-type cells were projected into the cyst lumens and lack of stromal invasion. In 2 cases of malignant Brenner tumors, different degrees of nuclear atypial transitional-type cells exhibited stromal invasion. Immunohistochemical stains for CK7, GATA3, p63 and CK5/6 were positive in all cases. Ki-67 was less than 5% in Brenner tumors, and up to 20%-30% in malignant Brenner tumors. Conclusion: Brenner tumors are mostly seen in postmenopausal patients and are usually benign. Imaging examination and usual ovarian tumor markers do not provide diagnostic value. Diagnosis and classification of Brenner tumors depend on histopathological evaluation.

[Comprehensive analysis of the effect of null zone shifting surgery treatment on patients with infantile nystagmus syndrome].

Objective: To characterize the postoperative change of eyes related parameters of patients with infantile nystagmus syndrome(INS), so as to provide a reference for the clinical evaluation of postoperative effect and the rational arrangement of patients' follow-up time after operation. Methods: A retrospective study. Clinical and follow-up data of 17 patients diagnosed with INS at Department of Ophthalmology in Xinhua Hospital, School of Medicine, Shanghai Jiaotong University from June 2014 to December 2016 were collected. All patients with abnormal head posture (AHP) underwent null zone shift surgery. The operative methods were Parks 5-6-7-8, Anderson, Kestenbum 5-5-6-4,null zone shift combined with strabismus correction and vertical null zone transposition. Ophthalmological examination and eye movement were recorded, including best corrected binocular visual acuity (BCBVA), position of the null zone, expanded nystagmus acuity function (NAFX) and foveation time. Single factor repeated analysis of variance, independent sample t test and rank sum test were used for statistical analysis. Results: Among the 17 children, 6 were females and 11 were males. The age at surgery of the patients was 5-11 years.The follow-up time was (14.8±6.0) months. Preoperative BCBVA was 0.382±0.147 (corrected posture), 0.300±0.056 (AHP); foveation time was (0.594±0.011)s;position of null zone was 23.570°±0.118°. The BCBVA at three months after operation was 0.318±0.044 (corrected posture), 0.260±0.045 (AHP); foveation time was (0.950±0.146)s; position of null zone was 5.360°±1.107°. The BCBVA at six months after operation was 0.264±0.039 (corrected posture), 0.230±0.037 (AHP);foveation time was (1.496±0.233) s; position of null zone was 6.070°±1.303°. The BCBVA at twelve months after operation was 0.309±0.039 (corrected posture), 0.250±0.045 (AHP);foveation time was (1.455±0.201) s; position of null zone was 9.290°±8.520°. There was statistical difference between the data of pre-operation and post-operation(all P<0.05). Change of null zone position was identified in six patients after six months.The preoperative NAFX of patients with presence of change of null zone positon was 0.308±0.063 (the primary position), 0.393±0.210 (null zone); BCBVA was 0.450±0.043 (corrected posture), 0.417±0.031 (AHP); foveation time was 0.122 (0.080-1.014)s. The postoperative NAFX of those patients was 0.430±0.090(the primary position), 0.471±0.140 (null zone); foveation time was 0.438(0.170-1.450) s. The data above were lower than that of patients with no regression of null zone[0.523±0.142,0.601±0.110,0.200±0.063,0.250±0.076,0.725(0.230-1.440)s,0.610±0.160,0.680±0.120,0.975(0.380-2.000)s]. The difference was statistically significant(all P<0.05). Conclusions: Null zone shifting surgery is an effective approach for treating INS. Reduction in the null zone position can be observed in some patients at 6 months after operation, which was related to NAFX, BCBVA and foveation time. It is recommended to extend the follow-up time to at least 6 months after the operation. (Chin J Ophthalmol, 2019, 55:13-19).

[Analysis of silica dust detection results in workplace air of somewhere in enterprise].

Objective: To understand the occupational hazard and distribution of silica dust (free SiO(2)≥10%) in the workplace environment of the enterprises in Fengxian District, and to provide scientific basis for improving the working environment and protecting the physical and mental health of the workers. Methods: Individual sampling monitoring and on-site labor hygiene investigation were conducted on 421 workers involved in 87 silicon dust enterprises in the jurisdiction from 2014 to 2018, and measured concentration-time weighted average (C(TWA)) . Results: The results showed that the range of the C(TWA) was (0.021~17.000) mg/m(3), the median was 1.600 mg/m(3), and the qualified rate of 30.88%. The difference of total dust concentration was statistically significant in different years (Z=38.831, P<0.05) . The qualified rate of small-scale enterprises is higher than that of medium-scale enterprises (χ(2)=9.472, P<0.05) . The qualified rate of other domestic enterprises is higher than that of private enterprises and foreign enterprises (χ(2)=10.089, P<0.05) . The acceptance rate of metal products manufacturing is lower than that of general equipment manufacturing and other manufacturing enterprises (χ(2)=64.626, P<0.05) . The qualification rate of natural ventilation is higher than that of mechanical ventilation (χ(2)=6.278, P<0.05) . Conclusion: The enterprises involved in silicon production in Fengxian District need to further strengthen the production process reform and improve the ventilation and dust removal protection measures. Widely carry out the publicity of occupational disease prevention and control law, conduct targeted pre-job training, improve workers' awareness of self-protection, and protect the occupational health of workers in many ways.

[Clinical analysis of cervical intraepithelial lesion in postmenopausal women].

Objective: To investigate the pathological escalation after cervical cone resection in postmenopausal women, and analyze the related influencing factors. Methods: A retrospective cohort study was conducted at the Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University between July 2013 and January 2015. Seven hundred and fifty cases of cervical cone-cut were enrolled in this study, 129 cases of them were postmenopausal women, and 621 were premenopausal women. All results of patients' liquid-based thin-layer cytology (TCT) , HPV test, colposcopy and biopsy pathology, cervical cone resection and postoperative pathological examination were collected. Then the compliance with the pathological examination results after colposcopic cervical biopsy and cervical cone resection, and the related factors affecting the pathological escalation after cervical cone resection were analyzed. The pathological escalation of patients with different menopausal conditions after cervical cone resection was also analyzed. Results: (1) Of the 750 patients, there were 329 patients had the same pathological examination results after colposcopic cervical biopsy and cervical cone resection, which accounted for 43.9% (329/750) . And 216 cases demonstrated pathological escalation after cervical cone resection, which accounted for 28.8% (216/750) . The results of TCT examination and menopause were significantly correlated with the pathological escalation after cervical cone resection (P<0.05) . However, the condition of HPV infection was unrelated to pathological escalation after cervical cone resection (P>0.05) . (2) Compared with the different results of TCT examination [including non-intrusive load monitoring (NILM) , atypical squamous cell of undetermined signification (ASCUS) , low-grade squamous intraepithelial lesion (LSIL) , high-grade squamous intraepithelial lesion (HSIL) ], the ratio of pathological escalation after cervical cone resection was not statistically significant difference between postmenopausal and non-menopausal patients (P>0.05) . The proportion of pathological escalation of patients with >5 years of menopause was significantly higher than that of patients with menopause time ≤5 years (40.3% vs 27.7%, OR=1.8, 95%CI: 1.1-2.8, P=0.029) . Among them, when the result of TCT examination was LSIL, the rate of pathological escalation in patients > 5 years of menopause was significantly higher than that in menopause time ≤5 years (6/10 vs 26.3%, OR=4.2, 95%CI: 1.1-15.8, P=0.033) . While the results of TCT examination were NILM, ASCUS or HSIL showed there was no statistically significant difference between two groups (P>0.05) . (3) Among the 143 cases, of which the result of TCT examination was LSIL, 9 cases of the pathological examination results after cervical resection were escalated to cervical cancer, which accounted for 6.3% (9/143) . Among 10 cases of menopause time >5 years, 2 cases (2/10) of the pathological examination results after cervical cone resection were escalated to cervical cancer. Among 133 cases with menopause time ≤ 5 years, 7 cases (5.3%) were upgraded to cervical cancer after cervical cone resection. The ratio of pathological escalation to cancer in postmenopausal patients with >5 years was higher than that of menopause time ≤5 years. Due to the data volume limitation, the comparison was not statistically significant difference (χ2=0.460, P>0.05) . Conclusions: In postmenopausal women, especially when menopausal time is > 5 years, the proportion of pathological escalation after cervical cone resection following colposcopic cervical biopsy is increased. And the pathological escalation after cervical cone resection is significantly correlated with the results of TCT examination and menopausal status. Therefore, doctors should treat the colposcopic biopsy pathological results with caution during clinic. Depending on TCT results, loop electrosurgical excision procedure (LEEP) sampling could be administrated directly in case of avoid missing diagnosis.

[KRAS mutations analysis in mucinous epithelial lesions of the endometrium].

Objective: To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features. Methods: The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups. Results: The patients'age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05). Conclusion: The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.