Autophagy-related tumor subtypes associated with significant gene expression profiles and immune cell infiltration signatures to reveal the prognosis of non-small cell lung cancer.

Autophagy plays an important role in non-small cell lung cancer (NSCLC). We aimed to establish novel autophagy-related tumor subtypes to distinguish the prognosis of NSCLC. In this study, gene expression profiles, mutation data and clinical information obtained from the Cancer Genome Atlas. Kaplan Meier-plotter could evaluate prognostic value of autophagy-related genes. Consensus clustering revealed autophagy-related tumor subtypes. Gene expression profiles, mutation data and immune infiltration signatures were identified, oncogenic pathways and gene-drug interactions were performed according to the clusters. Finally, a total of 23 prognostic genes were screened and consensus clustering analysis divided the NSCLC into 2 clusters. The mutation signature showed that 6 genes are special. Immune infiltration signatures showed that higher fraction of immune cells was associated with cluster 1. The oncogenic pathways and gene-drug interactions also showed different patterns. In conclusion, autophagy-related tumor subtypes have different prognosis. Understanding the subtypes of NSCLC are helpful to accurately identify the NSCLC and personalized treatment.

DNMT3a-Mediated Enterocyte Barrier Dysfunction Contributes to Ulcerative Colitis via Facilitating the Interaction of Enterocytes and B Cells.

Objective: Dysfunction of the enterocyte barrier is associated with the development of ulcerative colitis (UC). This study was aimed at exploring the effect of DNMT3a on enterocyte barrier function in the progression of UC and the underlying mechanism. Method: Mice were given 3.5% dextran sodium sulphate (DSS) in drinking water to induce colitis. The primary intestinal epithelial cells (IECs) were isolated and treated with lipopolysaccharide (LPS) to establish an in vitro inflammatory model. We detected mouse clinical symptoms, histopathological damage, enterocyte barrier function, B cell differentiation, DNA methylation level, and cytokine production. Subsequently, the effect of DNMT3a from IECs on B cell differentiation was explored by a cocultural experiment. Result: DSS treatment significantly reduced the body weight and colonic length, increased disease activity index (DAI), and aggravated histopathological damage. In addition, DSS treatment induced downregulation of tight junction (TJ) protein, anti-inflammatory cytokines (IL-10 and TGF-ß), and the number of anti-inflammatory B cells (CD1d+) in intestinal epithelial tissues, while upregulated proinflammatory cytokines (IL-6 and TNF-α), proinflammatory B cells (CD138+), and DNA methylation level. Further in vitro results revealed that DNMT3a silencing or TNFSF13 overexpression in IECs partly abolished the result of LPS-induced epithelial barrier dysfunction, as well as abrogated the effect of IEC-regulated B cell differentiation, while si-TACI transfection reversed these effects. Moreover, DNMT3a silencing decreased TNFSF13 methylation level and induced CD1d+ B cell differentiation, and the si-TNFSF13 transfection reversed the trend of B cell differentiation but did not affect TNFSF13 methylation level. Conclusion: Our study suggests that DNMT3a induces enterocyte barrier dysfunction to aggravate UC progression via TNFSF13-mediated interaction of enterocyte and B cells.

Analysis of a patient with tuberous sclerosis complex due to mosaicism TSC2 mutation / 中华医学遗传学杂志

OBJECTIVE@#To analyze variants of TSC1 and TSC2 genes in a Chinese patient with tuberous sclerosis complex (TSC).@*METHODS@#Peripheral blood samples were collected from the patient and her parents with informed consent. Following extraction of genomic DNA, potential variants of the TSC1 and TSC2 genes was detected by using targeted capture next-generation sequencing (NGS) and Sanger sequencing.@*RESULTS@#The patient was found to harbor a de novo mosaicism variant c.3295_3298delG (Val1100CysfsTer3) of the TSC2 gene, with the proportion of the mutant allele determined as 13.4%, which was confirmed by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3295_3298delG (Val1100CysfsTer3) variant was predicted to be pathogenic (PVS1+PS2+PM2).@*CONCLUSION@#The mosaicism heterozygous variant of c.3295_3298delG of the TSC2 gene, as detected by both NGS and Sanger sequencing, probably underlay the TSC2 in this patient.

Correlation of Global Strain Rate and Left Ventricular Filling Pressure in Patients with Coronary Artery Disease: A 2-D Speckle-Tracking Study.

The aim of the present study was to evaluate the role of 2-D speckle-tracking imaging in the prediction of left ventricular filling pressure in patients with coronary artery disease (CAD) and normal left ventricular ejection fraction (LVEF). Eighty-four patients with CAD and 30 healthy controls were recruited prospectively. The longitudinal strain rate (SR) curves were determined in three apical views of the left ventricle long axis. Circumferential and radial SR curves were determined in three short-axis views. Left ventricular end-diastolic pressure (LVEDP) was invasively obtained by left heart catheterization. Compared with the 30 controls, the patients with CAD had significantly lower global SR during early diastole (SRe) and higher E/SRe in three directions of myocardial deformation. CAD patients with elevated LVEDP had significantly lower SRe and higher E/SRe of three deformations. Pearson's correlation analysis revealed that LVEDP correlated positively with E/E' ratio, radial SRe and longitudinal and circumferential E/SRe. LVEDP correlated negatively with longitudinal and circumferential SRe and radial E/SRe. Receiver operating characteristic curve analysis revealed that these SR indexes predicted elevated LVEDP (areas under the curve: longitudinal E/SRe = 0.74, circumferential E/SRe = 0.74, circumferential SRe = 0.70, longitudinal SRe = 0.69, radial E/SRe = 0.68, radial SRe = 0.65), but neither was superior to the tissue Doppler imaging index E/E' (area under the curve = 0.84). The present study indicates that 2-D speckle-tracking imaging is a practical method for evaluating LV filling pressure, but it might not provide additional advantages compared with E/E' in CAD patients.

Evaluation of Left Ventricular Diastolic Dysfunction with Early Systolic Dysfunction Using Two-Dimensional Speckle Tracking Echocardiography in Canine Heart Failure Model.

BACKGROUND: This study evaluated the role of two-dimensional speckle tracking echocardiography (2DSTE) for predicting left ventricular (LV) diastolic dysfunction in pacing-induced canine heart failure. METHODS: Pacing systems were implanted in 8 adult mongrel dogs, and continuous rapid right ventricular pacing (RVP, 240 beats/min) was maintained for 2 weeks. The obtained measurements from 2DSTE included global strain rate during early diastole (SRe) and during late diastole (SRa) in the longitudinal (L-SRe, L-SRa), circumferential (C-SRe, C-SRa), and radial directions (R-SRe, R-SRa). Changes in heart morphology were observed by light microscopy and transmission electron microscopy at 2 weeks. RESULTS: The onset of LV diastolic dysfunction with early systolic dysfunction occurred 3 days after RVP initiation. Most of the strain rate imaging indices were altered at 1 or 3 days after RVP onset and continued to worsen until heart failure developed. Light and transmission electron microscopy showed myocardial vacuolar degeneration and mitochondrial swelling in the left ventricular at 2 weeks after RVP onset. Pearson's correlation analysis revealed that parameters of conventional echocardiography and 2DSTE showed moderate correlation with LV pressure parameters, including E/Esep' (r = 0.58, P < 0.01), L-SRe (r = -0.58, P < 0.01), E/L-SRe (r = 0.65, P < 0.01), and R-SRe (r = 0.53, P < 0.01). ROC curves analysis showed that these indices of conventional echocardiography and strain rate imaging could effectively predict LV diastolic dysfunction (area under the curve: E/Esep' 0.78; L-SRe 0.84; E/L-SRe 0.80; R-SRe 0.80). CONCLUSION: 2DSTE was a sensitive and accurate technique that could be used for predicting LV diastolic dysfunction in canine heart failure model.

Prediction of Left Ventricular Filling Pressure by 3-Dimensional Speckle-Tracking Echocardiography in Patients With Coronary Artery Disease.

OBJECTIVES: The purpose of this study was to investigate the diagnostic value of 3-dimensional (3D) speckle-tracking echocardiography for estimating left ventricular filling pressure in patients with coronary artery disease (CAD) and a preserved left ventricular ejection fraction. METHODS: Altogether, 84 patients with CAD and 30 age- and sex-matched healthy control participants in sinus rhythm were recruited prospectively. All participants underwent conventional and 3D speckle-tracking echocardiography. Global strain values were automatically calculated by 3D speckle-tracking analysis. The left ventricular end-diastolic pressure (LVEDP) was determined invasively by left heart catheterization. Echocardiography and cardiac catheterization were performed within 24 hours. RESULTS: Compared with the controls, patients with CAD showed lower global longitudinal strain, global circumferential strain, global area strain, and global radial strain. Patients with CAD who had an elevated LVEDP had much lower levels of all 4 3D-speckle-tracking echocardiographic variables. Pearson correlation analysis revealed that the LVEDP correlated positively with the early transmitral flow velocity/early diastolic myocardial velocity (E/E') ratio, global longitudinal strain, global circumferential strain, and global area strain. It correlated negatively with global radial strain. Receiver operating characteristic curve analysis revealed that these 3D speckle-tracking echocardiographic indices could effectively predict elevated left ventricular filling pressure (LVEDP >15 mm Hg) in patients with CAD (areas under the curve: global longitudinal strain, 0.78; global radial strain, 0.77; global circumferential strain, 0.75; and global area strain, 0.74). These parameters, however, showed no advantages over the commonly used E/E' ratio (area under the curve, 0.84). CONCLUSIONS: Three-dimensional speckle-tracking echocardiography was a practical technique for predicting elevated left ventricular filling pressure, but it might not be superior to the commonly used E/E' ratio in patients with CAD who have a normal left ventricular ejection fraction.

Lower gastrointestinal bleeding: role of 64-row computed tomographic angiography in diagnosis and therapeutic planning.

AIM: To determine the value of computed tomographic angiography (CTA) for diagnosis and therapeutic planning in lower gastrointestinal (GI) bleeding. METHODS: Sixty-three consecutive patients with acute lower GI bleeding underwent CTA before endovascular or surgical treatment. CTA was used to determine whether the lower GI bleeding was suitable for endovascular treatment, surgical resection, or conservative treatment in each patient. Treatment planning with CTA was compared with actual treatment decisions or endovascular or surgical treatment that had been carried out in each patient based on CTA findings. RESULTS: 64-row CTA detected active extravasation of contrast material in 57 patients and six patients had no demonstrable active bleeding, resulting in an accuracy of 90.5% in the detection of acute GI bleeding (57 of 63). In three of the six patients with no demonstrable active bleeding, active lower GI bleeding recurred within one week after CTA, and angiography revealed acute bleeding. The overall location-based accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the detection of GI bleeding by 64-row CTA were 98.8% (249 of 252), 95.0% (57 of 60), 100% (192 of 192), 100% (57 of 57), and 98.5% (192 of 195), respectively. Treatment planning was correctly established on the basis of 64-row CTA with an accuracy, sensitivity, specificity, PPV and NPV of 98.4% (248 of 252), 93.3% (56 of 60), 100% (192 of 192), 100% (56 of 56), and 97.5% (192 of 196), respectively, in a location-based evaluation. CONCLUSION: 64-row CTA is safe and effective in making decisions regarding treatment, without performing digital subtraction angiography or surgery, in the majority of patients with lower GI bleeding.

Serum Gamma-glutamyltransferase Levels Predict the Progression of Coronary Artery Calcification in Adults With Type 2 Diabetes Mellitus.

Progression of coronary artery calcification (CAC) may be more predictive of future coronary heart disease events than a baseline CAC score. We determined whether serum gamma-glutamyltransferase (GGT) activity can independently predict the progression of CAC in adults with type 2 diabetes mellitus (T2DM). Patients (n = 326) without symptomatic cardiovascular (CV) disease were evaluated by CAC imaging. The CAC scores were assessed at baseline and after 20 ± 4 months. Serum GGT activities were significantly higher in progressors compared with nonprogressors (39 ± 16 vs. 27 ± 11 U/L, P < .001). Multivariable analyses demonstrated that GGT activity retained a strong association with CAC progression after adjustment for CV risk factors. Additionally, there was a graded association between GGT activity quartile and annualized CAC progression. In asymptomatic patients with T2DM, we prospectively found that serum GGT activity may be an independent predictor of CAC progression but not a predictor of CAC incidence.

Clinical features and genetic analysis of 17 cases of glucose-6-phosphate dehydrogenase deficiency in Guizhou province / 中华实用儿科临床杂志

Objective To explore the clinical and genetic characteristics of 17 cases with glucose-6-phosphate dehydrogenase(G6PD) deficiency in Guizhou,China.Methods The clinical features of 17 patients with G6PD deficiency were analyzed,DNA samples were obtained from the patients and some mothers,and the exons and flanking intronic sequences of the G6PD gene were analyzed by the polymerase chain reaction and sequencing.Results The cases had diverse phenotypes,these patients had acute haemolytic anaemia triggered by eating broad beans,infections,ingestion of specific drugs or the neonatal period and chronic nonspherocytic haemolytic anaemia.Three cases of the patients had concomitant diseases for α Mediterranean anemia,acute myeloid leukemia M2 type and neonatal anal membrane stenosis,respectively.G1376T,G1388A and A95G were the commonest G6PD variants in patients in Guizhou,China.G1376T,G1388A and A95G mutations were observed in 82.4％ cases.Two patients had only compound variants(c.1311 C ＞ T,IVS11 nt 93 T ＞ C).One case in the Rongjiang County,Guizhou Province had novel compound variants (c.G1388A,IVS10-10 T ＞ G) in the world.A patient's mother in the Guiyang City,Guizhou Province,China had compound variants (c.1376 G ＞ T,1311 C ＞ T,IVS11 nt 93 T ＞ C) as a carrier.Conclusions G6PD deficiency has a wide range of clinical heterogeneity.A novel G6PD compound variant haplotype c.G1388A,IVS10-10 T ＞ G was first found in the world,and the SNP spectrum of G6PD was enlarged.There may be a G6PD compound variant haplotype c.1376 G ＞ T,1311 C ＞ T,IVS11 nt 93 T ＞ C in Guizhou.

Measurement and comparison of retinal nerve fiber layer thickness in different stages of diabetic retinopathy patient with type 2 diabetes / 中华实验眼科杂志

Background Diabetic retinopathy (DR) is one of the leading causes that result in adult irreversible blindness in many countries.Recent researches suggest that neurodegeneration is an important component of DR.To realize the disease process of retinal neutron is very important for prevention and treatment on DR.Objective This study was to investigate the change of retinal nerve fiber layer thickness in patients with type 2 diabetes mellitus.Methods Ninety-six eyes of 48 patients with type 2 diabetes mellitus were enrolled in Peking Union Medical College Hospital.The patients were assigned into non-diabetic retinopathy (NDR) group,background diabetic retinopathy(BDR) group,proliferative diabetic retinopathy (PDR) group and panretinal photocoagulation (PRP) group based on the fundus finding and fundus fluorescein angiography(FFA),and 24 normal subjects with matched age were included as control group.RNFL thickness was measured by GDxVCC system,including temporal,superior,nasal,inferior,total,(TSNIT) average,superior average,inferior average,TSNIT standard deviation and nerve fiber indication.The datas of the RNFL thickness were analyzed and comparison among different groups by one-way analysis of variance and Student Newman Keuls test.Results The TSNIT averages of the NDR group,BDR group,PDR group and PRP group were(56.54±5.28),(56.92±6.49),(53.04±6.14) and(53.17±9.30) μm,respectively,while that of the control group was (59.04±4.37) μm.The TSNIT average,superior average,inferior average,TSNIT standard deviation of the PDR group and PRP group compared with control group were significantly decreased,and the nerve fiber indication of the PDR group and PRP group was significantly increased (P =0.002,0.000,0.002,0.000,0.001 ;P =0.002,0.000,0.001,0.000,0.000).Compared with the control group,the TSNIT average,superior average,inferior average,TSNIT standard deviation were insignificantly decreased,and the nerve fiber indication was insignificantly increased in the NDR group and BDR group (P =0.187,0.235,0.333,0.106,0.202 ;P=0.262,0.063,0.072,0.098,0.062).Conclusions The decline of the RNFL thickness appears prior to DR findings.The RNFL thinning of PDR and PRP patients suggests the degeneration of neurons and atrophy of axonal.The neurodegeneration is an important component of DR.

Evaluation of bFGF effect on corneal collagen and nerve recovery following LASIK with confocal microscopy / 中华实验眼科杂志

Background Basic fibroblast growth factor(bFGF)secreted by cornea after injury is important to cytothesis,collagen fibers reconstruction and axons recovery.However,the local bFGF is not enough for the reparation process.Objective This study aimed to observe the findings of corneal collagen and nerve recovery under the confocal microscopy through focusing(CMTF) in the eyes with intervene of exogenous recombinant bFGF(rbFGF) after excimer laser in situ keratomileusis(LASIK).Methods LASIK rabbit models were binocularly created in 34 clean New Zealand white rabbits.The tobramycin combined with dexamethasone were dropped after operation for 10 days in bilateral eyes.rbFGF was topically administered in the right eyes of rabbits from 1 day through 3 months after LASIK,and lubricant was used in the left eyes at the same way.The corneal collagen and nerve recovery,keratocyte and endothelial cell counting were observed with CMTF at the 1st week,2nd week,2nd month,3rd month and 5th month after LASIK.Results Total 19 rabbits were meted the request of LASIK models.The keratocyte densities in anterior stroma of both groups reached the lowest level at the 2nd week and the highest level at the 3rd month.Otherwise,haze changed on the contrary.No statistically significant differences were found in anterior stroma keratocyte densities,haze grade,grey value between rbFGF group and lubricant group at various time points after operation(P＞0.05).The nerve cord densities of both groups were increased gradually,and those under the epithelial basement membrane were more dominant.The nerve density of the anterior stroma of rbFGF group was significant higher than the lubricant one in the 2nd group(P=0.038).The considerably elevated the subepithelial nerve density value was also seen in rbFGF group compared with lubricant at 5 months after operation(Z=-2.060,P=0.039).No any corneal neovascularization occurred in both groups through experiment duration.The positive correlation was found between grey value with haze grade in rbFGF group(b=22.687,F=37.975,P=0.000) and lubricant group(b=20.410,F=18.516,P=0.000).However,haze grade was not significant correlated with stromal keratocyte density(rbFGF group:b=0.001,F=0.164,P=0.668;lubricant group:b=-0.002,F=1.896,P=0.178).Conclusion Exogenous bFGF can improve the recovery of corneal nerve and regeneration of keratocyte after LASIK.No evidence of bFGF promoting corneal neovascularization is found in this experiment.

Application of octopus 101 GKP kinetic and static automated perimetry in the diagnosis of the primary open angle glaucoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical significance of the Octopus 101 GKP kinetic and static automated perimetry in the diagnosis of the primary open angle glaucoma (POAG).</p><p><b>METHODS</b>Thirty POAG patients (POAG group) and 34 normal individuals (control group) were detected with Octopus 101 GKP static and kinetic perimetry with GKP and TOP program from October 2006 to March 2007. The visual acuity, intraocular pressure (IOP), cupping/disc (C/D) ratio, mean defect (MD), loss variance (LV), areas of isopter, and testing time were analyzed.</p><p><b>RESULTS</b>The mean visual acuity, mean IOP and mean C/D ratio were significantly different between POAG group and control group (P = 0.000), and so was the testing time (P = 0.001). The mean test time was (307.78 +/- 134.50) s in the POAG group and was (228.12 +/- 75.33) s in the normal group. No linear correlation was found between the IOP and the areas of isopter or MD between these two group. The visual parameters (I 2e and III 4e) as to the areas of isopter of POAG were significantly different (P = 0.000), and so were the MD, LV and areas of isopter (P = 0.000). Static perimetry had a sensitivity of 80% and a specificity of 45%, and kinetic perimetry had a sensitivity of 86% and a specificity of 63%. The combined method of static and kinetic approaches had a sensitivity of 90%.</p><p><b>CONCLUSIONS</b>The Octopus 101 GKP static and kinetic perimetry can perform an automated test that combines the advantages of both kinetic and static perimetry, resulting in a decreased subjectivity and individual difference by adjusting the response time and improved accuracy of test results. By changing stimulus size, background illumination, and stimulus angular velocity, the combination of the kinetic and static test may provide a higher sensitivity in the diagnosis of the early stage of POAG, particularly in patients with early peripheral visual field defect.</p>

Expressions of Nogo-A mRNA and Nogo Receptor mRNA in Hippocampus of Immature Rats after Febrile Seizures / 实用儿科临床杂志

Objective To explore the changes of Nogo-A mRNA and Nogo receptor(Ng-R) mRNA expressions in hippocampus of immature rats after febrile seizures(FS).Methods One hundred and twenty-seven male SD rats(15 days) were randomly divided into control group(immersed in 37 ℃ water,n=40)and hyperthermia treated group(immersed in 44.5 ℃ water,n=87).The latter was further divided into febrile control group(n=42) and FS group(n=45) according to whether seizures occurred or not.Each group was further divi-ded into 5 groups according to different therapies(1,3,5,7,10 times treatment).Then 5 cases of the 8 rats were randomly used to observe the expressions of Nogo-A mRNA,Ng-R mRNA in hippocampus by using reverse transcriptase polymerase chain reaction(RT-PCR).Three of the 8 rats were randomly used to observe the changes of neurons and mossy fiber sprouting(MFS) in hippocampus by Nissl and Timm staining.Results 1.No seizures occurred in normal control group.Seizures occurred in 2 rats of febrile control group.In FS group,various seizures occurred such as nodding spasms,tonic seizures,clonic seizures and tonic-clonic seizures,2 rats died of drowning and 3 rats died of status epilepticus.2.The expressions of Nogo-A mRNA,Ng-R mRNA in the immature rats′ hippocampus became up-regulated after the 7th and 10th seizure,significantly higher than those of the other 2 control groups(Pa

Early Manifestation of Childhood Autism / 实用儿科临床杂志

Objective To explore the early manifestation of childhood autism.Methods Fifty-one childhood autism were selected as autistic group,and 40 cases of healthy children were selected as healthy control group.All children were investigated retrospectively about social competence,language development,repetitive motor actions and special interests before 18 month-old by questionnaire.All results were analyzed by SPSS 11.5 software.Results Compared with healthy control group,children in autistic group presented a series of abnormal manifestations before 18 month-old,including social competence,language development,repetitive motor actions and special interests(Pa

Visual fields changes in chronic angle closure glaucoma patients after their intraocular pressures were well controlled / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the progression of visual field loss and to explore the prognosis of glaucomatous optic neuropathy in patients with chronic angle-closure glaucoma (CACG) after their intraocular pressures were well controlled under 21 mmHg.</p><p><b>METHODS</b>Forty-seven eyes of 29 patients in the Department of Ophthalmology in PUMC Hospital were included. All the patients had at least two separate tests of visual fields using the 24-2 program of the Humphery Visual Field Analyzer after their intraocular pressure were well controlled under 21 mmHg after sugery. The visual fields of patients were followed routinely for at least 1 year. In addition, all patients were divided into 2 groups according to follow-up period: 1-2 years group and over 2 years group. Visual field scores were calculated with the Advanced Glaucoma Intervention Study (AGIS) method. The visual fields were divided 5 sections and the sensitivity and defect depth of each section were calculated.</p><p><b>RESULT</b>No statistically significant differences were found in terms of AGIS scores, localized sensitivities and localized defects within the time interval of the observation.</p><p><b>CONCLUSION</b>Glaucomatous optic neuropathy is not likely to progressively deteriorate in CACG cases once their intraocular pressure are well controlled under 21 mmHg.</p>