Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective To investigate the pathological changes of spinal cord tissues after spinal cord injury and their significance for clinical diagnosis and treatment of complete spinal cord injury.Methods Patients with complete spinal cord injury were selected.Mter rigorous ethical review and patient informed consent,damaged section of the spinal cord and necrotic tissue were removed and transplanted with the function biological material with autologous stem cell.The specimen of injured spinal cord collected during the operation were divided into three phases according to injury time:3 cases of acute phase (≤ 3 days),3 cases of subacute phase (4-14 days),and 1 case of chronic phase (＞ 14 days).The pathological changes of injured spinal cord tissue were observed through HE staining,and the expression of hypoxia inducible factor 1α (HIF-1α),tumor necrosis factor (TNF-α),microtubule-associated protein(MAP2) were detected by immunofluorescence.Results (1) HE staining showed that the acute injury mainly manifested as diffuse hyperemia and liquefaction,subacute injury infiltration of inflammatory cells and spinal cord liquefaction,and chronic injury mainly scar repair.(2)The fluorescence intensity (24.67 ±0.51) of HIF-1o in chronic injury was higher than acute (3.17 ± 0.40) and subacute injury (4.62 ± 0.48) (P ＜ 0.05),and the fluorescence intensity of subacute injury was higher than that of acute injury (P ＜ 0.05).(3) The fluorescence intensity (17.60 ± 1.17) of TNF-α in subacute injury was higher than that of acute injury (5.35 ± 0.33) and chronic injury (1.81 ± 0.17) (P ＜0.05);(4) The fluorescence intensity of MAP2 was 9.46 ±0.41 in acute injury,higher than 3.25 ± 0.42 in subacute injury and 1.16 ± 0.08 in chronic injury (P ＜ 0.05).Conclusions There are hypoxia,inflammation,neuronal apoptosis and repair in the spinal cord tissues after complete spinal cord injury,such as hyperemia,liquefaction,necrosis and gradual scar repair.The severity of inflammation and hypoxia significantly differs among different injury phases.The inflarmnatory cytokines are mainly active in the microenvironment during subacute injury.Hypoxia is mainly involved in the pathological changes of chronic injury.This can provide a new theoretical basis for the clinical treatment of complete spinal cord injury and the timing of surgical treatment.

Objective To investigate the association between leukoaraiosis (LA) and early neurological deterioration (END) in patients with acute ischemic stroke.Methods Clinical data of 328 patients with acute ischemic stroke admitted in the hospital from January 2013 to January 2016 were retrospectively reviewed.According to the changes of National Institute of Health Stroke Scale (NIHSS) scores within 72 h after admission,88 patients (26.8%) were identified as END.Clinical manifestations,laboratory tests and radiographic findings were compared between END group and non-END group.ResultsUnivariate analysis indicated that age [(74.6±11.0) vs.(70.7±11.8) years,t=2.67,P=0.01],female sex [51.1% (45/ 88) vs.38.8%(93/240),χ2=4.05,P=0.04],initial NIHSS [M(Q1,Q3) 6(3,9) vs.3 (2,6),χ2=-4.38,P=0.00],systolic blood pressure [(155±28) vs.(149±20) mmHg(1 mmHg=0.133 kPa),t=2.04,P=0.04],responsible artery occlusion [18.2% (16/88) vs.8.3%(20/240),χ2=6.39,P=0.01],white cell count [(7.8±2.7) 109 vs.(7.1±2.2) 109,t=2.32,P=0.02],fasting blood glucose [(7.2±2.6) vs.(6.6±2.4) mmol/L,t=2.00,P<0.05] and C-reactive protein level [(24.5±27.1) vs.(14.6±23.2) g/L,t=3.25,P=0.00] were significantly different between END group and non-END group.After adjustment of confounding factors,LA in periventricular with Fazekas grade 2 (OR=2.309,95%CI: 1.070-4.984,P=0.03) and Fazekas grade 3 (OR=2.861,95%CI: 1.214-6.742,P=0.02) and LA in centrum semiovale with Fazekas grade 3 (OR=3.047,95%CI: 1.244-7.461,P=0.02) were independently associated with END.Conclusion Leukoaraiosis in periventricular group and centrum semiovale are associated with early neurological deterioration in patients with acute ischemic stroke.

Objective: To study the value of three-dimensional(3D) visualization in the diagnosis and surgical treatment for pancreatic tumor. Methods: From June to September 2016, 26 patients with pancreatic tumors in Jinling Hospital, Medical School of Nanjing University were involved. The study included 26 patients(8 females and 18 males) with mean age of (57±12)years (ranging from 23 to 77 years). And there were 20 malignant tumors and 6 benign tumors. All of them were examined with abdominal thin slice CT scanning and the CT images were imported into 3D visualization system for 3D visualization. The main elements examined by 3D visualization included tumor shape, size, and location; distribution and morphology of the peripancreatic lymph node; the relationships among neoplasms, organs and blood vessels. Results: Among the 26 patients, there were 21 cases with pancreatic cancer, of which 15 cases successfully underwent standard pancreatectomy. All patients were operated underwent accurate assessment. The 3D model demonstrated the origination and bifurcations of blood vessels, and the relationships among neoplasms, organs and blood vessels efficiently. The 3D technique could facilitate to evaluate response of neiadjuvant chemotherapy in the pancreatic cancer patients (n=5).3D reconstruction could detect the lymph-node metastases accurately (n=12) in patients with pancreatic cancer. 3D reconstruction were applied to evaluate the the size and range of tumor on 5 cases. Conclusions 3D reconstruction allows stereoscopic identification of the spatial relationships between physiologic and pathologic structures.The 3D technique could facilitate to evaluate distribution and morphology of the peripancreatic lymph node, and to evaluate the relationships among neoplasms, organs and blood vessels.

Background Primary angle-closure glaucoma (PACG) is the most common type of glaucoma in China.A screening to identify the possible angle closure is important in the prevention and treatment of PACG.Objective This study was to determine the characteristics and the optimal parameters measured by the scanning peripheral anterior chamber depth analyzer (SPAC) in the screening of occludable angle of a sample of adult Chinese population.Methods A cross-sectional study was performed in Handan from February to April in 2013.One hundred and eighty Chinese adults were enrolled with the age of 40 years and older and acceptable criteria during 5-year following-up duration of the Handan Eye Study.Routine eye examinations were carried out in all subjects under the informed consent,including visual acuity,optometry,anterior ocular segment examination under the slit lamp microscope,and then SPAC measurement and gonioscopy were performed in a dark room.Occludable angle was defined as posterior trabecular meshwork being invisible in ≥ 180° range under the static gonioscope.Occludable angle by SPAC was estimated using available central chamber depth (ACD) and a combined indicator,numerical grade was 5 or fewer and/or the categorical grade was S or P,separately.Receiver operating characteristic (ROC) curve was calculated to assess the performance of these parameters in detecting eyes with occludable angle for the population-based sample,and area under curve (AUC) was drown to compare the screening efficiencies between available ACD and combined indicator.Results In 180 subjects,occludable angles were found in 62 and open angles were in 118.Compared to the subjects with open angle,the subjects with occludable angle showed the older age (P＜0.001),more females (P＜0.05),lower visual acuity (P＜0.001),greater hyperopic diopter (P＜0.05),smaller ACD value (P＜0.001) and shorter axial length(P＜0.001).In eyes with occludable angle by using SPAC,the ACD showed an AUC of 0.832.Using a cutoff of 2.7 mm for ACD,the sensitivity and specificity were 85.48％ and 68.64％,and under the cutoff of 2.8 mm,the sensitivity and specificity was 90.32％ and 61.02％,respectively.For the combined parameters,the sensitivity and specificity was 62.90％ and 90.68％,respectively and the AUC was 0.768.Conclusions When gonioscopy is used as a reference,a cutoff of 2.8 mm ACD by SPAC shows the highest sensitivity for the screening of occludable angle in Chinese population.

Background Myopia is one of the main blinding diseases worldwide.At present,a lot of studies on ocular structure focus on the changes of corneal curvature(CC),central corneal thickness (CCT),anterior chamber depth (ACD),ocular axial length (AL) and choroid and retina,but the research of anterior chamber angle section structure form and ciliary body shape is lack.Objective This study was to measure and analyze the changes of the anterior chamber angle and related tissue structure in myopic eyes.Methods One hundred and forty-nine eyes of 149 subjects were included from May 2008 to May 2010 in Eighth Hospital of Qingdao City with the ages of 18-40years old under the informed consent.The subjects were assigned to the emmetropia group (30 eyes) ([0.02±0.18] D),low myopia group(46 eyes) ([-1.64±0.69] D),moderate myopia group (35 eyes) ([-4.56±0.66] D) and high myopia group (38 eyes) ([-7.04 ± 1.02] D).Conventional indexes including intraocular pressure (IOP),CCT,CC,AL and ACD were measured,and the indexes including chamber angel open distance (AOD),iris thickness (IT1,IT2,IT3),the position of ciliary body such as A-angel,B-angel,trabecular ciliary process distance (TCPD),irisciliary process distance (ICPD) and ciliary body thickness (CBT1,CBT2,CBT3) were measured by ultrasound biomicroscope(UBM).Results The IOP,CC and CCT values showed slight change in different groups without remarkable difference among them (all at P＞0.05).As the increase of myopic degree,AL was extended and ACD was deepened,showing significant differences among the groups (both at P＜0.05).There were no significant differences in IT1,IT2 and IT3 among the four groups (all at P＞0.05).However,the measuring values of angle opening degree (TIA and AOD500),ciliary position (A-angle,B-angle,TCPD,ICPD) and CBT (CBT1,CBT2,CBT3) elevated with the increase of myopic degree (all at P＜0.05).Positive correlations were found between AOD500 and ACD,A-angle,CBT1,CBT2,AL,negative correlations was found between AOD500 and myopic degree (r =0.573,0.513,0.325,0.398,0.542,-0.435,all at P＜0.01);Positive correlations were found between TIA and ACD,A-angle,CBT1,CBT2,AL,negative correlations was found between AOD500 and myopic degree (r =0.573,0.464,0.276,0.410,0.539,-0.435,all at P ＜ 0.01).Conclusions Within certain limits,as the increase of myopic degree,ACD deepens,the anterior chamber angle widens,ciliary process thickens and ciliary body backward shifts.

BACKGROUNDAssessment of the optic disc and retinal nerve fiber layer (RNFL) is essential for the diagnosis and monitoring of glaucoma. Knowledge of normal optic disc topography provides a benchmark for evaluating glaucomatous pathologic changes, especially in its early stages. The purpose of this study was to evaluate the characteristics and correlation factors of the optic disc parameters using the Heidelberg Retina Tomograph II (HRT II) in a large sample of normal eyes of adult Chinese subjects.

METHODSDisc data were obtained from 6 830 subjects aged >30 years from the Handan Eye Study. All participants underwent comprehensive eye examinations and physical examinations. The associations of gender, age, body mass index, blood pressure, waist-to-hip ratio; refractive error, intraocular pressure, axial length, and disc area were assessed using simple and multiple regression analysis. The correlation between HRT II parameters was evaluated.

RESULTSOf the 7 557 eligible subjects, 6 830 took part in the study (90.4% response rate) and 2 633 normal eyes with good-quality HRT II images were selected. The mean disc area was 2.28 mm(2) (standard deviation (SD) 0.43) and mean neural rim area was 1.80 mm(2) (SD 0.29). In multiple regression analysis, optic disc area significantly correlated with age, gender, and axial length (P < 0.001). All optic disc parameters showed a significant correlation with disc area (0.054

CONCLUSIONSThe optic disc area in rural Chinese population is larger than reported in white and Japanese populations, similar to that of Indian population and urban Chinese population. Most optic disc measurements were moderately or weakly affected by disc area. In addition to the RNFL, there may be other factors affecting the rim area. The relationship between optic disc and axial length may suggest a link between larger disc area, thinning of the lamina cribrosa, and increased glaucoma susceptibility in myopic eyes.

Adult ; Female ; Glaucoma ; epidemiology ; Humans ; Male ; Middle Aged ; Myopia ; epidemiology ; Optic Disk ; anatomy & histology

Background Early diagnosis of primary angle-closure glaucoma (PACG) and screening or case detection of high risk population have become a major challenge in the prevention and treatment of PACG.Commonly used methods for evaluation of anterior chamber depth (ACD) and anterior chamber angle nowadays have their shortcomings.Scanning peripheral anterior chamber depth analyzer (SPAC) measures ACD and evaluates the risk of angle closure.Also,SPAC is handy,objective and noninvasive.Objective This study was to evaluate the repeatability (within-rater differences) and reproducibility (between-rater differences) of SPAC to measure anterior chamber-related parameters and agreement of SPAC to estimate occludable angle between two operators.Methods A prospective cross-sectional study was designed.Thirty subjects with shallow ACD (modified van Herick grading≤ 3 and Shaffer grading≤2) aged 35 years and older,who met the inclusion criterion were enrolled as shallow anterior chamber group and 30 age-and gender-matched normal adults (modified van Herick grading≤3 and Shaffer grading≤2)from the follow-up research of the Handan Eye Study in February 2013.After an elementary eye examination,a randomly selected eye of each subject in both groups received three consecutive SPAC measurements by each of the two examiners,respectively to obtain ACD,central corneal thickness (CCT) and corneal radius of curvature (CRC).Meanwhile,the identity of occludable angle as the numerical grade was 5 or fewer and/or the categorical grade being S or P was also obtained.The repeatability of each examiner was evaluated by the repeatability limit (RL) and the reproducibility of the two examiners was evaluated by intraclass correlation coefficient (ICC).The agreement of occludable angle estimation between two operators was evaluated using Kappa coefficient.Results The RLs percentage for ACD,CCT and CRC ranged from 0.36％ to 3.29％,and 0.90％ to 4.72％ in the normal control group and shallow anterior chamber group from operator A,and those from operator B were 0.38％ to 2.55％,and 0.51％ to 3.42％.The ICCs for ACD,CCT and C RC of SPAC were 0.966,0.859,0.989 and 0.915,0.905,0.971,respectively from operator A and operator B.The Kappa coefficients for the identity of occludable angle between two operators were 1.000 and 0.520 in the normal control group and the shallow anterior chamber group,respectively.Conclusions Measurements of the three parameters provided by SPAC in normal and shallow anterior chamber subjects show a good repeatability and reproducibility.The results of identity of occludable angle from two examiners have a good agreement for normal subjects and a moderate reproducibility for subjects with shallow ACD.

OBJECTIVE:To discuss the interactions between tetracyclines(oxytetracycline,methacycline,tetracydine,and doxycycline)and human serum albumin(HSA).METHODS:The binding constants and the number of biding sites of tetracyclines with human serum albumin(HSA)at various temperatures were studied by using UV-visible absorption spectrum and spectrofluorimetry,and the enthalpy change(?H)entropy change(?S)were computed.According to the Frster nonradiative energy transfer theory,the critical distances R0 between donators and acceptors were derived.RESULTS:The thermodynamic parameters were as follows:?H0;R0:oxytetracycline:(1.82 nm),and methacycline(2.31 nm),tetracydine(2.98 nm),doxycycline(2.26 nm).CONCLUSION:Tetracyclines can all cause HSA's fluorescence quenching.The quenching mechanism is static quenching.The main acting force between them is electrostatic attraction.

0.05).No correlation was found between phosphate concentration and dft, dfs or CSI. Conclusions: There is no correlation between phosphate conc entration and caries status.