[Exploration and practice of artificial intelligence assisted primary vision health management].

It has attracted much attention worldwide that the application of artificial intelligence (AI) in primary screening and clinical diagnosis and treatment of eye diseases. In recent years, this technology has also been widely used in various grass-roots eye disease management, effectively improving the current situation of weak eye disease diagnosis ability and shortage of human resources in primary medical institutions. At present, there is no reference standard or guideline for the management mode, implementation content and management method of vision health management based on this technology, which are in urgent need of standardization. The article described the work mode exploration of AI-assisted grass-roots visual health management in Shanghai and shared practical experience. The aim is to provide reference for other provinces in China to carry out relevant work.

[Analysis of community intervention effects for diabetic eye diseases in Shanghai Xinjing community from 2016 to 2018].

Objective: To analyze the effects of community-based interventions for diabetic eye diseases in Xinjing community, Shanghai from 2016 to 2018. Methods: Based on the project of "Establishment of Service Model for Comprehensive Prevention and Treatment of Diabetic Eye Diseases in Shanghai", the participants were not suffering diabetic retinopathy (DR) in Xinjing community in 2016 before interventions and received community-based interventions for diabetic eye diseases. The incidence of DR, visual acuity and awareness of DR were used as evaluation indicators to analyze the effects of interventions for diabetic eye diseases in the community. Results: A total of 537 patients were included in this study, the incidence of DR among diabetic patients in Xinjing community was 7.6% after interventions. The duration of diabetes (OR= 1.065) and HbA1c (OR= 1.090) were the risk factors of DR. Before and after the interventions, the patients with monocular low vision and binocular low vision were 27 cases (5.0%), 8 cases (1.5%), 19 cases (3.5%) and 7 cases (1.3%) respectively. After interventions, the awareness on the prevention and treatment of DR increased significantly, and the proportion of regular visits to ophthalmology examination, diet control and physical exercise also increased significantly. Conclusion: Community-based interventions for diabetic eye diseases are helpful to improve the awareness of DR prevention and control, reduce the incidence of DR.

[Challenges of artificial intelligence used for eye disease screening in recent China communities].

Due to factors such as medical resources, public awareness, funding for general screening, or optimized screening models, community-based screening is far from meeting the demand. Artificial intelligence (AI) can replace some of the medical work and combine it with the "Internet+" model to transfer medical resources to improve accessibility and availability. However, the application of AI technology to community-based screening still faces many challenges, such as most AI products cannot be directly applied to community-based screening, the inability to integrate multimodal information such as medical history, symptoms, and images, and the lack of relevant regulations and health policies for productization and implementation. Therefore, we suggest that the relevant departments take actions: (1) to build standardized big data sets, unlock data barriers, and accelerate the development and application of AI technology; (2) to train "AI+" medical staffs as soon as possible; (3) to establish relevant laws and regulations; (4) to establish relevant R&D plans and quality standards and regulatory frameworks for AI products; (5) to encourage more investment in medical AI infrastructure in the central and western regions and remote and poor areas.

[Two-year follow-up study in type 2 diabetic patients with mild visual impairment].

Objective: To determine the 2-year visual prognosis in Chinese type 2 diabetic patients with mild visual impairment and identify the predictors factors. Method: This was a 2-year population-based cohort study. The study population consisted of 650 type 2 diabetic patients with bilateral mild visual impairment in 2014 who were followed up in 2016. The demographic information, systemic and ophthalmological examination results for each participant was collected. Mild visual impairment was defined as best-corrected visual acuity (BCVA)<20/25 to ≥20/63, moderate and severe visual impairment was defined as BCVA<20/63 to ≥20/400, blindness was defined as BCVA<20/400 following the International Council of Ophthalmology (ICO) 2002 definition. The two-year visual prognosis was divided into three groups: visual impairment regression, progression, and stable. Using chi-square test or independent t-test, the predictor factors of visual prognosis and the leading causes of visual impairment were studied. Results: 605 patients completed the follow-up in 2016. Among them, 477 were still bilateral mild visual impairment, accounting for 78.8% (477/605). The level of unilateral or bilateral visual impairment regressed in 8.1% (49/605), while progressed in 13.1% (79/605). Young age (t=2.7, P<0.05), short duration of diabetes (t=2.5, P<0.05), low blood glycemic hemoglobin (t=2.5, P<0.05) and total cholesterol (t=2.8, P<0.05) were associated with regression of visual impairment. Low levels of education (t=5.2, P<0.05), high blood glycemic hemoglobin (t=2.4, P<0.05) and total cholesterol (t=2.4, P<0.05)were associated with progression of visual impairment. Cataracts and diabetic retinopathy were the first and second cause of mild, moderate severe visual impairment or blindness. Conclusions: The percentage of 2-year visual acuity decline is relatively high in type 2 diabetic patients with mild visual impairment. We should strengthen blood glucose and cholesterol control to reduce the progress of visual impairment.(Chin J Ophthalmol, 2021, 57: 766-771).

[Analysis of cataract surgery status in public hospitals of Shanghai from 2013 to 2015].

Objective: To analyze the reasons that restrict the growth of cataract surgery service capacity in public hospitals in Shanghai in recent years. Methods: The status of surgeries performed in public hospitals are analyzed based on the data related to cataract surgery collected from the database of Shanghai Eye Disease Treatment. Meanwhile, the surgeries performed by ophthalmologists working in the public hospitals are studied based on the National ophthalmology service capacity questionnaire. Results: The cataract surgery volume performed in public hospitals of Shanghai increased from 45 480 in 2013 to 51 941 in 2015. In 2014, the year on year growth rate of cataract surgery volume in tertiary hospitals was 8.54%, while in 2015, it was -0.21% on an annual basis. More than 70% cataract surgeries were performed in tertiary public hospitals. For those performed in tertiary public hospitals, 80% were performed in urban area. The actual surgeons in tertiary account for 70% of the actual surgeons in all public hospitals. Among all cataract surgeries performed in secondary hospitals, half were performed in urban areas. The volume of cataract surgery by cataract surgeon and the number of the ophthalmologist were higher than those in secondary hospitals. The average cataract surgery volume of tertiary hospitals in urban areas and the average annual cataract surgery volume of the actual surgeons are much higher than those of the secondary hospitals in the urban areas, but it is contrary in exurban areas. Conclusion: The excessive density of tertiary hospitals in urban area and poor ophthalmology service capacity in secondary hospitals in suburban and exurban areas have restricted the rapid growth rate of cataract surgery and even a decline in Shanghai public hospitals. (Chin J Ophthalmol, 2020, 56: 615-620).

[Development and application of a fundus image quality assessment system based on computer vision technology].

Objective: To develop a fundus image quality assessment system based on computer vision technology and to verify its accuracy by comparing the results of artificial discrimination and using this system. Methods: The process of image evaluation was divided into four modules: fundus image preprocessing, fundus image quality evaluation, fundus image content detection and evaluation result output. The system was designed to automatically evaluate the image quality of each fundus image, identify the optic disc and macula, and judge whether the image was qualified or not according to the image quality discrimination rules. A total of 2 397 fundus images of 787 type 2 diabetes patients were selected as the test data set. The average age of the patients, including 384 males and 403 females, was (69.65±19.09) years old. The images were taken by the staff of community health service centers in Shanghai with a fundus camera. The fundus image quality assessment system was used to conduct quality control and classification of the data set. At the same time, 12 professional fundus picture readers were employed to conduct manual quality control and classification of this data set. The system quality control results and artificial quality discrimination results were compared and analyzed. Results: The fundus image quality assessment system automatically recognized left and right eyes and eye positions on the input fundus images. The quality control interface included four indicator lights, which respectively corresponded to the images with the optic disc or macula as the center of the left or right eye. Evaluation of each fundus image was completed within 1 second, and the results were automatically displayed on the user interface. The 2 397 fundus photos were identified manually as 1 846 qualified photos and 551 unqualified photos. Among the unqualified images, 62 (11.27%) were too dark, 51 (9.27%) were too bright, 59 (10.73%) were not clear in the macular area, 36 (6.54%) showed no macula or optic disc, 125 (22.73%) could not present the fundus structure, 175 (31.82%) were blurred, and 42 (7.64%) were blocked. The results of the system and manual assessment were consistent in 1 788 qualified images (96.86%) and 550 unqualified images (99.82%), with an overall consistency rate of 97.54%. Conclusion: The fundus image quality assessment system can achieve highly consistent results with the professional judgment of ophthalmologists and has the characteristics of objectivity. (Chin J Ophthalmol, 2020, 56:920-927).

[Analysis of cataract surgery cases from 2013 to 2015 in Shanghai].

Objective: To analyze the changes of cataract surgery volume and related influencing factors in Shanghai during 2013 and 2015. Methods: The information of Cataract patients during the period of 2013 and 2015 was collected from Shanghai Cataract Operations Database. The cataract surgery volume and CSR of Shanghai residents and non-registered ones were compared. The cataract surgery volume and CSR of registered Shanghai residents in urban, suburban and exurban areas were calculated, respectively. In addition, the sources of surgery cost, hospitals where surgeries were performed were analyzed. Results: In Shanghai, the cataract surgery volume grew from 63 915 to 114 688 and the total CSR grow from 2 686 to 4 729 during the years between 2013 and 2015. In this period, the cataract surgery volume of registered Shanghai residents in urban, suburban and exurban areas increased from 27 203, 21 921, 8 847 to 46 415, 40 463, 18 171, respectively. The CSR1 (CSR of registered Shanghai residents) grew rapidly from 4 081 to 7 363, while the CSR2 (CSR of non-registered Shanghai residents) grew slowly from 619 to 949. According to statistics, 93.08% of the registered Shanghai residents paid the medical expenses with their medical insurance, while more than 80% non-registered Shanghai residents afforded it at their own expenses. The number of total CSR in urban, suburban and exurban areas increased from 5 085, 3 600, 3 205 to 3 600, 6 588, 6 513 respectively. In 2015, the number of cataract surgery cases in non-public hospitals exceeded that in public hospital, accounting for 54.71% of the total cataract surgeries. In the same year, 55.44% of the total cases come from suburban and exurban residents. Conclusions: From 2013 to 2015, there had been a dramatic increase in cataract surgery volume in nonpublic hospitals and exurban area in Shanghai, which effectively solved the problem of low CSR in suburban and exurban area, however the 1ow level of CSR of non-registered Shanghai residents was the key factor that significantly reduced the total CSR in Shanghai. (Chin J Ophthalmol, 2018, 54:580-585).

[An investigation of lanthanum and other metals levels in blood, urine and hair among residents in the rare earth mining area of a city in China].

Objective: To investigate the levels of lanthanum, cerium, praseodymium, and neodymium in the blood, urine, and hair samples from residents in the rare earth mining area of a city in China, and to provide a scientific basis for the control of rare earth pollution and the protection of population health. Methods: A total of 147 residents who had lived in the rare earth mining area of a city for a long time were selected as the exposure group, and 108 residents in Guyang County of this city who lived 91 km away from the rare earth mining area were selected as the control group. Blood, urine, and hair samples were collected from the residents in both groups. Inductively coupled plasma mass spectrometry was used to determine the content of lanthanum, cerium, praseodymium, and neodymium in blood, urine, and hair samples. Results: In the exposure group, the median levels of lanthanum, cerium, praseodymium, and neodymium were 0.854, 1.724, 0.132, and 0.839 µg/L, respectively, in blood samples, 0.420, 0.920, 0.055, and 0.337 µg/L, respectively, in urine samples, and 0.052, 0.106, 0.012, and 0.045 µg/g, respectively, in hair samples. The exposure group had significantly higher levels of the four rare earth elements in blood, urine, and hair samples than the control group (P<0.01) . Conclusion: The residents in the rare earth mining area of this city have higher content of lanthanum, cerium, praseodymium, and neodymium in blood, urine, and hair than those in the non-mining area; the content of cerium is highest, followed by lanthanum, neodymium, and praseodymium.

[Investigation of pregestational diabetes mellitus in 15 hospitals in Guangdong province].

Objective: To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods: A total of 41 338 women delivered in the 15 hospitals during the 6 months, 195 women with PGDM (PGDM group) and 195 women with normal glucose test result (control group) were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups. In the PGDM group, pregnancy outcomes were analyzed in women who used insulin treatment (n=91) and women who did not (n=104). Results: (1) The incidence of PGDM was 0.472%(195/41 338). Diabetes mellitus were diagnosed in 59 women (30.3%, 59/195) before pregnancy, and 136 women (69.7%,136/195) were diagnosed as PGDM after conceptions. Forty-six women (33.8%) were diagnosed by fasting glucose and glycohemoglobin (HbA1c) screening. (2) The maternal age, pre-pregnancy body mass index (BMI) , prenatal BMI, percentage of family history of diabetes, incidence of macrosomia, concentration of low density lipoprotein were significantly higher in PGDM group than those in control group (all P<0.05). Women in PGDM group had significantly higher HbA1c concentration ((6.3±1.3)% vs (5.2±0.4)%) , fasting glucose [(6.3±2.3) vs (4.8±1.1) mmol/L], oral glucose tolerance test (OGTT) -1 h glucose ((12.6±2.9) vs (7.1±1.3) mmol/L) and OGTT-2 h glucose [(12.0±3.0) vs (6.4±1.0) mmol/L] than those in control group (P<0.01). (3) The morbidity of preterm births was significantly higher (11.3% vs 1.0%, P<0.01), and the gestational age at delivery in PGDM group was significantly smaller [(37.6±2.3) vs (39.2±1.2) weeks, P<0.01]. Cesarean delivery rate in the PGDM group (70.8% vs 29.7%) was significantly higher than the control group (P<0.01). There was significantly difference between PGDM group and control in the neonatal male/female ratio (98/97 vs 111/84, P=0.033). The neonatal birth weight in PGDM group was significantly higher ((3 159±700) vs (3 451±423) g, P<0.01) . And the incidence of neonatal hypoglycemia in the PGDM group was higher than the control group (7.7% vs 2.6%, P=0.036). (4) In the PGDM group, women who were treated with insulin had a smaller gestational age at delivery [(36.9±2.9) vs (37.9±2.5) weeks, P<0.01], and the neonates had a higher neonatal ICU (NICU) admission rate (24.2% vs 9.6%, P<0.01). Conclusions: The morbidity of PGDM in the 15 hospitals in Guangdong province is 0.472%. The majority of PGDM was diagnosed during pregnancy; HbA1c and fasting glucose are reliable parameters for PGDM screening. Women with PGDM have obvious family history of diabetes and repeated pregnancy may accelerate the process of diabetes mellitus. Women with PGDM have higher risk for preterm delivery and neonatal hypoglycemia. Unsatisfied glucose control followed by insulin treatment may increase the need for NICU admission.

[Treatment of single one-stage posterior atlantoaxial fixation in Chiari malformation].

Objective: To explore the effects of surgical technique of single one-stage posterior C(1-2) screw rod fixation of Chiari malformation (CM) associated with occipitalization and without atlantoaxial dislocation. Methods: A total of 23 patients with CM treated between January 2014 and October 2015 in Department of Neurosurgery of Chinese People's Liberation Army General Hospital were retrospective reviewed. All of them were diagnosis with CM associated with occipitalization and without atlantoaxial dislocation, including 8 males and 15 females, aging from 11 to 57 years (mean (35.5±10.52) years). Single one-stage posterior C(1-2) screw rod fixation with bone grafting fusion was performed. Operation time and intraoperative blood loss were recorded. Japanese Orthopaedic Association (JOA) scores and Odom rating were used to evaluate the clinical effects at pre- and post-operative. Regression of the cerebellar tonsillar was measured by MRI. The results were analyzed by paired samples t test. Results: Twenty-three patients were implanted screws successfully, the vertebral artery injury and cerebrospinal fluid leakage were not found. The mean operation time was (172.7±19.9) minutes, the intraoperative blood loss was (153.9±49.3) ml. Compared to preoperative, the JOA score increased (13.7±1.6 vs. 11.5±1.4) and the tonsillar herniation decreased ((0.8±0.6)cm vs. (1.9±0.6) cm) in the last follow-up, there were statistical difference (t=13.386, P<0.01; t=17.995, P<0.01). The results of the postoperative Odom grading were as follows: 6 cases were perfect (26.1%), 13 cases were good (56.5%), 4 cases were moderate (17.4%) and no case was poor.No signs of instrument loosen or screw broken was noticed. 100% bony fusion rate was achieved. The follow-up time was 6 to 23 months (mean (10.5±3.2) months). One case developed internal fixator related discomfort, the symptom was relieved by internal fixator removal surgery performed 4 months after the operation when osseous fusion had already been achieved. No new neurologic symptoms were observed in other 22 patients. Conclusions: The results of the study substantiates the effectiveness of single one-stage posterior fixation strategy for CM, which is associated with occipitalization and without atlantoaxial dislocation. This technique could be an alternative choice for this type of CM.

[A cross-sectional study of cataract in residents with type 2 diabetes living in Xinjing Town, Shanghai].

Objective: To investigate the prevalence, subtypes and risk factors of cataract in type 2 diabetic individuals. Methods: Geographically defined cluster sampling method was used in this population-based, cross-sectional study. There were 7 756 type 2 diabetes individuals in Xinjing Town with a residential population of 88 864. The type 2 diabetic individuals were randomly selected from 20 basic sample units in Xinjing Town of Changning District from April to June 2016. All participants received visual acuity measurement and eye examination. The standard of lens opacity assessment was according to the Lens Opacities Classification SystemⅡ(LOCSⅡ). The prevalence of cataract in diabetic individuals was calculated with LOCS≥2. Multivariate Logistic regression analysis was used to explore the relevant factors of cataract in type 2 diabetic individuals. Results: A total of 1 719 type 2 diabetic individuals were included in the analysis. There were 682 men (39.67%) and 1 037 women (60.33%) in this population. There were 434 cataract individuals and the prevalence of cataract was 25.25%. There were 269 cases of nuclear type (15.7%), 38 cases of cortical type (2.2%), 2 cases of posterior subcapsular type (0.12%) and 42 cases of mixed type (2.4%) in the 1 719 individuals. Multivariate Logistic regression analysis showed that age (P<0.001), duration of diabetes (P<0.001), education (P=0.005), fasting blood glucose (P(6.1-7.7mmol/L)=0.025, P(7.8-24.3mmol/L)=0.022, compared with 3.6-6.0 mmol/L of fasting blood glucose), and ocular axial length (P<0.001) were associated with cataract. Conclusion: Cataract is a common ophthalmic disease in adults with type 2 diabetes in Xinjing Town. Regular screening of diabetes in the high risk population and intensive control of both glucose and blood pressure in diabetic patients are recommended to prevent and delay the development of cataract. (Chin J Ophthalmol, 2017, 53: 489-494).

[Research advances in diabetic retinopathy telescreening systems].

Diabetic retinopathy has become the main cause of the sight impairment and blindness among the adult population. Early detection of diabetic retinopathy helps to prevent and reduce the damage to eyesight. The development of diabetic retinopathy telescreening systems has been rapid. The operation modes, key technologies, economic benefits and new progression of diabetic retinopathy telescreening systems are reviewed. (Chin J Ophthalmol, 2016, 52: 868-871).

[The study of establishment of the " Chinese provincial Blindness prevention technical guidance group performance evaluation system"].

Objective: To establish an assessment system, including indexes and scoring methods, that can be used for performance evaluation of the provincial blindness prevention technical guidance group properly and effectively . Methods: The indexes and scoring methods were set based on the core content of The " National Plan of Prevention and Treatment of Blindness (2012-2015)" , the specific requirement and target of the World Health Organization (WHO) "For the General Eye Health: Global plan of Action (2014-2019)" , and the current situation of the China's provinces and autonomous regions. These indexes should be of effectiveness, feasibility, comparability, guidance and advancing. Formed by a literature review of candidate indicators, the framework of the system is built by qualitative assessment. With the Delphi method, the system was further revised and improved. Empirical pilot study was then used to prove the feasibility, followed by the final qualitative analysis that establish the " Chinese provincial Blindness prevention technical guidance group performance evaluation system" . Results: Through the literature review and qualitative assessment, a six dimensional system framework was built, including 6 first-level indicators, 16 second-level indicators, and 29 third-level indicators through Delphi method evaluation. With the variation coefficient method, the coeffiences of the first-level index weight were calculated as: Organization and management 0.15, Development and implementation of blindness prevention plans 0.15, Implementation of blindness prevention projects 0.14, Training 0.17, Health education 0.18, and Cooperation and exchanges 0.21. The specific scoring method for this system is confirmed as: data and files check, field interview, and record interview, sampling investigation. Empirical pilot study was conducted in the Jilin, Guizhou and Gansu provinces, and the self-assessment results from local experts were consistent with the scores from the systems. Conclusion: This system established is appropriate at current time, and it can effectively evaluate the performance of the Chinese provincial Blindness prevention technical guidance group. (Chin J Ophthalmol, 2016, 52:814-824).

[A cross-sectional study of moderate or severe visual impairment and blindness in residents with type 2 diabetes living in Xinjing Town, Shanghai].

Objective: To investigate the prevalence, underlying causes and risk factors of moderate or severe visual impairment and blindness in a population with type 2 diabetes in Xinjing Town, Shanghai, China. Methods: A cross-sectional survey among local Han adult residents, who were previously diagnosed as type 2 diabetes, was conducted between October 2014 and January 2015. The survey was preceded by a pilot study; operational methods were refined and quality assurance evaluation was carried out. The best corrected visual acuity was recorded and classified following the modified World Health Organization grading system. Assigned ophthalmic doctors assured the leading causes of every blind or visually impaired eye. Binary logistic regression analysis was used to determine the related factors of blindness and moderate or severe visual impairment. Results: A total of 2 216 type 2 diabetic residents were enrolled, and 166 eyes (3.7%, 166/4 432) were blind. Cataract was the leading cause of blindness (39.8%); macular degeneration (18.0%) and eyeball atrophy (11.4%) were the second and third leading causes of blindness, respectively. Moderate or severe visual impairment was found in 376 eyes (8.5%, 376/4 432), and the most frequent cause was cataract (65.7%), followed by diabetic retinopathy (9.8%) and macular degeneration (9.4% ). Older age, female gender, earlier onset diabetes and a lower spherical equivalent in the better eye were associated with best corrected visual acuity<20/63 in the better eye. Conclusion: The prevalences of moderate or severe visual impairment and blindness in our population with type 2 diabetes were high. (Chin J Ophthalmol, 2016, 52: 825-830).

Combined genetic and imaging diagnosis for two large Chinese families affected with Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder characterized by nystagmus, impaired motor development, ataxia, and progressive spasticity. Genetically defective or altered levels of proteolipid protein (PLP1) or gap-junction alpha protein 12 gene have been found to be a common cause. Here we report on two large Han Chinese families affected with this disease. The probands of both families had produced sons featuring cerebral palsy that had never been correctly diagnosed. PMD was suspected after careful analysis of family history and clinical features. Three rounds of molecular testing, including RT-PCR, genetics linkage and SRY sequence analyses, in combination with fetal ultrasound and magnetic resonance imaging, confirmed the diagnosis. In Family 1, in addition to two patients, three carriers were identified, including one who was not yet married. Genetic testing indicated that a fetus did not have the disease. A healthy girl was born later. In Family 2, two patients and two carriers were identified, while a fetus was genetically normal. A healthy girl was born later. We concluded that by combining genetic testing and imaging, awareness of the symptoms of PMD and understanding of its molecular biology, there is great benefit for families that are at risk for producing offspring affected with this severe disease.

MiR-638 serves as a tumor suppressor by targeting HOXA9 in glioma.

OBJECTIVE: MiR-638 is constantly downregulated and serves as a tumor suppressor in various cancers. Its role in gliomas remains unclear. This study is designed to investigate the clinical significance and the pathogenic role of miR-638 in human gliomas. PATIENTS AND METHODS: Quantitative Real-time PCR was performed to analyze the expression of miR-638 in the tumor and adjacent tissues of 24 glioma patients. The association between the expression of miR-638 and clinical features were examined. Survival of patients was studied by Kaplan-Meier curves. The impact of miR-638 on cell growth and apoptosis was determined by CCK-8 assay, colony formation assay, cell cycle analysis and Annexin V-FITC-PI apoptosis assay. The effect of miR-638 on HOXA9 was determined by luciferase assay and Western blot. The effect of miR-638 and HOXA9 on expression of oncogenes, Cyclin D1 and C-MYC was determined by Western blot. RESULTS: MiR-638 expression was constantly downregulated in glioma tumor tissue, which is negatively correlated with the WHO grade. MiR-638 expression was associated with clinical features such as tumor size, KPS score and WHO grade. Patients with low miR-638 had a worse overall survival than those with high expression. Experimentally, miR-638 directly targeted HOXA9 to suppress its expression, leading to attenuations of cell proliferation, colony formation and cell cycle progression and enhanced basal apoptosis level. MiR-638/HOXA9 axis also suppressed the expression of Wnt/beta-catenin-regulated oncogenes, Cyclin D1 and C-MYC. CONCLUSIONS: MiR-638 is a constantly downregulated microRNA in gliomas and is associated with its prognosis. MiR-638 regulates cellular malignancy of gliomas through targeting HOXA9. Thus, miR-638/HOXA9 signaling axis may have therapeutic potential in gliomas.

Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats.

The contributions of amiloride-sensitive and -insensitive fractions of alveolar fluid clearance in adult ventilated rats were studied under control conditions and after beta-adrenergic stimulation. Rats were instilled with a 5% albumin solution containing terbutaline (10(-4) M) or dibutyryl-cGMP (DBcGMP; 10(-4) M) with or without the cyclic nucleotide-gated cation channel inhibitor l-cis-diltiazem (10(-3) M) and/or amiloride (10(-3) M). Alveolar fluid clearance over 1 h was 18 +/- 2% in controls. In controls, amiloride inhibited 46 +/- 15% of alveolar fluid clearance, whereas l-cis-diltiazem had no inhibitory effect. Terbutaline and DBcGMP stimulated alveolar fluid clearance by 85 +/- 3 and 36 +/- 5%, respectively. Amiloride and l-cis-diltiazem inhibited nearly equal fractions of terbutaline-stimulated alveolar fluid clearance when given alone. Amiloride and l-cis-diltiazem given together inhibited a significantly larger fraction of alveolar fluid clearance in terbutaline-stimulated rats and in DBcGMP-stimulated rats. Based on these data, terbutaline stimulation recruited both amiloride-sensitive and l-cis-diltiazem-sensitive pathways. In contrast, DBcGMP mainly recruited l-cis-diltiazem-sensitive pathways. Therefore, the amiloride-insensitive fraction of Na+-driven alveolar fluid clearance may be partly mediated through cyclic nucleotide-gated cation channels and activated by an increase in intracellular cGMP.

alpha-adrenergic blockade restores normal fluid transport capacity of alveolar epithelium after hemorrhagic shock.

Activation of beta-adrenergic receptors in the lung is an important mechanism that can prevent alveolar flooding after brief but severe hemorrhagic shock. However, a neutrophil-dependent oxidant injury to the alveolar epithelium prevents the normal upregulation of alveolar fluid clearance by catecholamines after prolonged hemorrhagic shock. Because hemorrhage increases proinflammatory cytokine expression in the lung partly through the activation of alpha-adrenergic receptors, the objective of this study was to determine whether alpha-adrenergic blockade would restore the normal fluid transport capacity of the alveolar epithelium after hemorrhagic shock. Hemorrhagic shock was associated with a significant increase of interleukin-1beta (IL-1beta) concentration in the lung and a failure of the alveolar epithelium to respond to beta-adrenergic agonists, with the upregulation of vectorial fluid transport despite intra-alveolar administration of exogenous catecholamines. In contrast, catecholamine-mediated upregulation of alveolar liquid clearance was restored by pretreatment with phentolamine, an alpha-adrenergic-receptor antagonist. Phentolamine pretreatment also significantly attenuated the shock-mediated increase of IL-1beta concentration in the lung. Additional experiments demonstrated that the inhibition of IL-1beta binding to its receptor by the administration of IL-1-receptor antagonist restored the normal fluid transport capacity of the alveolar epithelium after hemorrhagic shock. In summary, the results of these studies indicate that the activation of alpha-adrenergic receptors after hemorrhagic shock prevents the beta-adrenergic-dependent upregulation of alveolar fluid clearance by modulating the severity of the pulmonary inflammatory response.