[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.

[Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People's Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events. Results: A total of 81.82% (n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546-1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% (n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients (n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion: Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

[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.

Low levels of organic compound trace elements improve the eggshell quality, antioxidant capacity, immune function, and mineral deposition of aged laying hens.

In the egg production industry, trace elements are required as additional dietary supplements to play vital roles in performance and egg quality. Compared to inorganic microelements (ITs), appropriate dose of organic trace microelements (OTs) are environmentally friendly and sufficient to satisfy the needs of hens. In order to evaluate the extent to which low-dose OTs replace whole ITs, the effects of organic copper, zinc, manganese, and iron compound on the performance, eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens were investigated. A total of 1 080 57-week-old Jing Hong laying hens were assigned to five groups with six replicates of 36 layers each for an 8-week experimental period. The birds were fed either a basal diet (control treatment (CT)) or the basal diet supplemented with commercial levels of inorganic trace elements (IT 100%) or the equivalent organic trace elements at 20%, 30%, and 50% of the inorganic elements (OT 20%, OT 30%, and OT 50%, respectively). Results showed that compared with those in the CT treatment, feeding hens with inorganic or organic microelement diet had significant effects on the eggshell quality, antioxidant capacity, immune function, and mineral deposition of old laying hens (P < 0.05). The eggshell strength and ratio between OT 30%, OT 50%, and IT 100% were similar at weeks 4 and 8, and the eggshell thickness of these groups was also similar at weeks 6 and 8. At week 8, the eggshell colour in OT 50% was darker than that in IT 100%. The mineral content in the eggshells of OT 50% and IT 100% significantly increased (P < 0.001), with no significant difference in effective thickness, mammillary thickness, and mammillary knob width between groups. There were no differences in the malondialdehyde content, total antioxidant capacity, and total superoxide dismutase activity in serum between OT 30%, OT 50%, and IT100%. While the catalase activities, the interleukin-1ß, interleukin-10, immunoglobulin G, and immunoglobulin M concentrations in serum were not significantly different between OT 50% and IT 100%. The mineral contents in the faeces of the organic groups were considerably reduced compared with those in IT 100% (P < 0.001). In conclusion, dietary supplementation with 30-50% organic compound microelements has the potential to replace 100% inorganic microelements in the hen industry for improving eggshell quality, mineral deposition in the eggshell, antioxidant capacity, and immune function, and reducing emissions to the environment without negative effects on laying performance.

[Preliminary audiological evaluation of the SoundBite bone conduction devices in adults with single-sided deafness].

Objective: The auditory deficits of single-sided deafness (SSD) can be treated with a novel intra-oral device, SoundBite, which delivers sound by applying vibratory signal to the teeth. The purpose of this study was to evaluate the efficacy and benefit of the bone conduction device for Chinese adults with SSD. Methods: Eighteen patients aged 19-66 yrs with acquired, permanent sensorineural SSD and no current treatment by any other devices for SSD, were recruited in a prospective controlled, nonrandomized, unblinded study. They were requested the continually daily wear of the new device over a 30-day free trial period. The intra-oral hearing device was placed around two maxillary teeth and was similar to a small partial denture or retainer. The audiological tests included pure tone air conduction thresholds, monosyllable word recognition score (WRS) in quiet and sentence reception thresholds in noise (via CMNmatrix test). The benefit was determined with the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire. Results: The monosyllable WRS and the 50% threshold of signal-to-noise ratio (SNR50) were significantly better in all aided conditions. The head shadow effect, assessed by the SNR50 via CMNmatrix test improved an average of 2.6 dB after 30 days' wearing compared with unaided condition (P<0.001). The APHAB scores improved (P<0.05) for all subjects for the Global and Ease of Communication, Reverberation, Background Noise subscales. The SSQ scores improved (P<0.05) for all subjects for Speech, Spatial and Qualities of Hearing subscales. Conclusion: The SoundBite is a good alternative to the well-established implantable bone conduction devices in patients with SSD. An improvement in listening ability in noise and quiet as well as a decrease of the head shadow effect is validated as the expected.

[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.

[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.

Effects of normal and low calcium and phosphorus levels and 25-hydroxycholecalciferol supplementation on performance, serum antioxidant status, meat quality, and bone properties of broilers.

To determine the effects of normal and low dietary calcium (Ca) and phosphorus (P) levels and 25-hydroxycholecalciferol (25-OH-D3) supplementation on performance, serum antioxidant status, meat quality, and bone properties of broilers, 224 1-day-old Arbor Acre male broilers were used in this study. Broilers were allotted randomly to 1 of 4 treatments in a 2 × 2 factorial arrangement that included normal or low Ca and P diet with or without 69 µg/kg 25-OH-D3. The trial consists of a starter phase from day 1 to 21 and a grower phase from day 22 to 42. Dietary 25-OH-D3 supplementation increased (P < 0.05) average daily weight gain from day 22 to 42 and decreased feed conversation ratio from day 22 to 42 and day 0 to 42. On day 21, 25-OH-D3 increased serum concentrations of total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase in broilers fed low Ca and P diet (Interaction, P < 0.05). 25-hydroxycholecalciferol significantly decreased serum malondialdehyde concentration. Dietary Ca and P deficiencies significantly decreased serum Ca and P concentrations and increased serum parathyroid hormone (PTH) concentration, and serum Ca and 25-OH-D3 concentrations were significantly increased by 25-OH-D3 supplementation. On day 42, serum T-AOC and CAT concentrations were decreased by dietary Ca and P deficiencies without 25-OH-D3 (Interaction, P < 0.05) and unaffected by dietary Ca and P deficiencies with 25-OH-D3. Dietary Ca and P deficiencies significantly decreased Ca, P, and alkaline phosphatase concentrations and increased PTH concentration in serum. Dietary 25-OH-D3 increased (P < 0.05) serum Ca and 25-OH-D3 concentrations and decreased (P < 0.05) serum tartrate-resistant acid phosphatase concentration. The interaction between CaP level and 25-OH-D3 was observed (P < 0.05) for tibial Ca content and femoral bone density. 25-hydroxycholecalciferol significantly increased tibial breaking strength. These data indicated that 25-OH-D3 supplementation at 69 µg/kg increased growth performance in some periods, enhanced serum antioxidant capacity, and improved bone mineralization and breaking strength of broilers.

[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.

[The prevalence and relationship between laryngopharyngeal reflux disease, anxiety and depression in otolaryngology outpatients].

Objective: To obtain the prevalence laryngopharyngeal reflux disease (LPRD), anxiety and depression in otorhinolaryngology outpatients and to explore the role of mental and psychological factors (anxiety and depression) in their pathogenesis. Methods: A questionnaire survey of reflux symptom index(RSI) scale and hospital anxiety and depression (HAD) scale were used to report 1 111 cases of outpatients in Department of Otorhinolaryngology Head and Neck Surgery, Peking University People's Hospital, from July 2017 to June 2018 (486 males, 625 females, age of 18-96 years old, median age of 38[30,53] years old) and to obtain the prevalence of LPRD, anxiety and depression. RSI-positive patients were selected in the case group, and RSI-negative patients were selected in the control group. The differences in HAD scores between the two groups were compared, and the risk factors of laryngopharyngeal reflux were analyzed. Statistical analysis was performed using SPSS 20.0 software. Results: There were 151 cases in the case group and 960 cases in the control group. The prevalence of LPRD was 13.59% (151/1 111).There was no significant difference in the prevalence of LPRD between different genders (P>0.05). The prevalence rate was the highest in the 18-40 age group, and the difference in the prevalence of all age groups (18~ 40 years old; 41-65 years old; >65 years old) was statistically significant (P<0.05). The prevalence of LPRD among smokers and non-drinkers was higher than that of non-smokers and non-drinkers and the prevalence of the two groups was statistically significant (P<0.05). The most common symptoms of the RSI scale were pharyngeal foreign body sensation (92.72%,140/151), persistent clearing throat (88.74%,124/151), excessive sputum or nasal reflux (82.12%, 124/151). There were significant statistical differences between the two groups (P<0.05). Ninty-one patients with anxiety, the prevalence was 8.19%(91/1 111); 76 patients with depression, the prevalence was 6.84%(76/1 111).Among the LPRD patients, the hospital anxiety scale scored 29.14% (44/151), and the hospital depression scale scored 17.22% (26/151). The scores of anxiety symptoms and depressive symptoms in the LPRD group were higher than those in the non-LPRD group. The above scores were statistically significant (P<0.05). Logistic regression analysis showed that smoking, anxiety and symptoms of gastroesophageal reflux disease were independent risk factors for laryngopharyngeal reflux. Conclusions: The prevalences of LPRD, anxiety and depression in the otorhinolaryngology clinic are 13.59%, 8.19% and 6.84%, respectively. Among patients with laryngopharyngeal reflux, the prevalence of anxiety is 29.14%, and the prevalence of depression is 17.22%. Age, smoking, drinking, alcohol consumption, education level, course of disease, symptoms of gastroesophageal reflux disease, pharyngeal foreign body sensation, etc. are related to LPRD. Mental factors (anxiety and depression) may play a role in LPRD. Smoking, anxiety symptoms and symptoms of gastroesophageal reflux disease are closely related to the incidence of LPRD.

[Investigation of laryngopharyngeal reflux prevalence and risk factors in otolaryngology].

Objective:To investigate the prevalence and related risk factors of laryngopharyngeal reflux in otolaryngology. Method:During January 2019 to March 2019, the inpatients in otolaryngology were investigated by the questionnaire of reflux symptom index scale and the laryngopharyngeal reflux related risk factors were analyzed. Result:Among the 227 patients, 33 patients with suspected LPR contained 19 patients（20.7%） of 92 patients in the laryngopharyngeal group, 10 patients（16.1%） of 62 patients in the nasal group, and 4 patients（5.5%） of 73 patients in the ear group. LPR prevalence in the laryngopharyngeal group was statistically different from that in the ear group（P<0.05）. Univariate logistic regression analysis showed that age, gender, smoking, drinking and BMI were risk factors of LPR（P<0.01）. Multivariate logistic regression analysis indicated that BMI was an independent risk factor of LPR（P<0.01）. Conclusion:LPR had a high prevalence rate in otolaryngology related diseases, and appropriate synergistic anti-LPR treatment could be carried out while treating otolaryngology related diseases.

AK5, a novel prognosis marker, inhibits apoptosis and promotes autophagy as well as proliferation in human gastric cancer.

OBJECTIVE: To explore the relationship between AK5 and gastric cancer. MATERIALS AND METHODS: The in situ levels of AK5 in the GC tissues from 255 patients were detected by immunohistochemistry (IHC). The correlation between AK5 expression and the clinicopathological parameters was analyzed by Pearson correlation, and the prognostic factors were identified by Cox regression analysis. The transcriptome data of 14 human GC cell lines deposited in the CCLE database were analyzed, and two lines were selected for functional studies. AK5 was knocked down in the AZ521 and MKN74 cells using siRNA, and their proliferation and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and Annexin-V staining, respectively. In addition, the apoptosis and autophagy of the markers were detected by Western blotting. RESULTS: Patients expressing high AK5 levels in the tumor tissues had significantly shorter survival compared to low-expressing group. In addition, AK5 expression was associated with T stage and N stage and was an independent prognostic factor. AK5 knockdown in the AZ521 and MKN74 cells significantly inhibited proliferation and autophagy, and increased apoptosis. CONCLUSIONS: AK5 is a potential prognostic marker and therapeutic target for GC.

[Establishment and research of a New Zealand rabbit model of laryngopharyngeal reflux].

Objective: To establish a New Zealand rabbit animal model of laryngopharyngeal reflux disease (LPRD) using esophageal balloon together with metal internal stent dilation and to investigate the changes of mucosa. Methods: 20 New Zealand rabbits were randomly divided into experimental group and control group, with 10 in each group. Balloon dilatation and metal internal stent dilation were carried out in experimental group to reproduce the animal model of LPRD.The middle of balloon was placed at the lower esophageal sphincter (LES) while the stent was placed at the upper esophageal sphincter (UES). The guide wire was placed in the control group, but the balloon was not expanded and the stent was not placed. The general condition, pH value of hypopharynx, laryngeal histopathology and changes of pepsin content of New Zealand rabbits were observed regularly. The difference between experimental group and control group was compared. Results: The 24-hour Dx-pH monitoring results showed that the number of reflux episodes(20.0[9.5, 35.0], 13.0[6.5, 22.0]), and the percent time below pH 5.5 (1.36%[0.60%, 4.57%], 1.36%[0.43%, 2.77%]) in the experimental group at the 2nd and 4th week were significantly different from those in the control group (0[0,3.0], 1.0[0.5, 3.8]; 0[0, 0.01%], 0[0, 0], respectively, all P<0.01), suggesting that the experimental group New Zealand rabbits developed LPRD. Compared with the control group under microscope, lymphocytes infiltration and submucosal gland hyperplasia increased in the mucosa of the throat of the experimental group. The results of pepsin immunohistochemical staining between the two groups were statistically significant (P=0.014). Conclusion: The use of balloon dilatation of the LES combined with metal stent dilatation of the UES can successfully establish a laryngopharyngeal reflux model, and lesions in the throat tissue can be observed.

PTEN expression in U251 glioma cells enhances their sensitivity to ionizing radiation by suppressing DNA repair capacity.

OBJECTIVE: Mutations in phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor gene, lead to altered sensitivity to drugs and radiation in various types of cancer. Restoring PTEN expression in tumor cells can increase radiosensitivity by inhibiting the repair of DNA double-strand breaks (DSBs). Thus, determining the mechanism of action of this protein may lead to novel therapeutic strategies. MATERIALS AND METHODS: In this study, we transduced U251 cells with a lentiviral vector expressing PTEN to examine the mechanism of radiosensitization. Specifically, we examined the formation of radiation-induced DNA DSBs and apoptosis, as well as the expression of several proteins involved in repairing DSBs (p53, ataxia-telangiectasia mutated, DNA-dependent protein kinase C, Ku70-80). RESULTS: Our results showed that PTEN transduction sensitized U251 cells to X-rays, increasing the number of DSBs per cell and fraction of cells undergoing apoptosis. Additionally, the average size of γH2AX nuclear foci was increased following irradiation. These findings were accompanied by a PTEN-dependent irradiation-independent increase in p53 levels and decrease in phosphorylated Ku70/80 levels. CONCLUSIONS: Our results suggest that PTEN affects radiosensitivity by reducing DSB repair and by enhancing the p53 pathway, leading to increased apoptosis.

[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.