Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Objective To study the characteristics of hyperphenylalaninemia (HPA) and the differences in blood and urine metabolic index and their correlation.Methods A total of 137 patients with HPA diagnosed by the Pediatric Inherit Metabolism and Endocrine Department,Guangdong Women and Children's Hospital,Guangzhou Medical University from January 2014 to June 2017,were enrolled.Tandem mass spectrometry (MS/MS),gas chromatography/ mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) were used to analyze the concentration of blood and urine metabolites in children,and the patients were divided into different groups according to the drug load test of tetrahydrobiopterin (BH4) and dihydrobiopterindine reductase (DHPR) deficiency.The HPA metabolite analysis of horizontal concentration by statistical differences and correlation analysis were performed.Results Among the 137 cases of HPA,there were 101 cases (73.7％) of phenylalanine hydroxylase deficiency (PAH),and among them 21 cases (15.3％) were classic phenylketonuria (PKU),37 cases were mild PKU (27.0％),43 cases (31.4％) wcrc mild HPA.Thcrc were 22 cases (16.1％) with BH4 reaction,and 79 cases (57.7％) of non-reactive type.Besides,there were 36 cases (26.3％) of tetrahydrobiopterin deficiency (BH4 D),of which 6-pyruvoyl tetrahydropterin synthase deficiency (PTPS) in 34 cases (24.8％) and dihydrobiopterindine reductase deficiency (DHPR) in 2 cases (1.5％).Urinary phenylacetic acid (r =0.673,P ＜ 0.01),phenyllactic acid (r =0.736,P ＜ 0.01),phenylpyruvic acid (r =0.642,P ＜ 0.01) were significantly correlated with blood phenylalanine (Phe) concentration,and the neopterin (N) (r =0.442,P ＜ 0.01) and biopterin (B) (r =0.398,P ＜ 0.01) had low correlation.Urinary phenylacetic acid,phenyllactic acid and phenylpyruvic acid had no correlation with urinary pterin.There were significant differences among PTPS deficiency group,BH4 response type,and non-reactive type(all P ＜ 0.05),but no significant difference between the BH4 reaction type and the non-reactive group (P ＞ 0.05).Conclusions Through the analysis of the different types of HPA metabolic profiles,it can help to master the incidence and characteristics in the region,within a certain concentration range of blood Phe,the phenylacetic acid,phenyllactic acid,phenylpyruvic acid should not be tested by GC-MS alone.Uterine erythropoietin analysis of BH4D classification and identification of BH4 reaction,non-reactive PKU have a supporting role,so master the metabolic index of various types of concentration and relevance of HPA,it can provide basis for early diagnosis,accurate treatment and follow-up.

Aim To investigate the effect of curcumin on radiosensitivity of radioresistant nasopharyngeal carcinoma cell line CNE-2R and its mechanism.Methods The concentration of curcumin was screened by MTT assay.Dose-survival curves were obtained according to the colony forming test for L-Q matching and multitarget-single hitting matching,while SF2 and the correlation parameters of radiation biology were calculated.The changes of cell cycle in CNE-2R cells caused by curcumin were also tested by flow cytometry(FCM).The differential expression of genes related to cell cycle and DNA damage repair were detected by RT-qPCR.Results CNE-2R cells could not be inhibited by 10 μmol·L-1 curcumin.Dealt with 10 μmol·L-1 curcumin for 24 h,the value of α/β increased to 1 596 from 6.56;the value of SF2 decreased to 0.361 Gy from 1.93 Gy;the value of N decreased to 1.06 from 1.60;the value of D0 decreased to 2.12 from 3.27;the value of Dq decreased to 0.12 from 1.53.FCM showed that the cells in G2 phase had a significant increase and the cells in S phase had a significant decrease after dealt with 10 μmol·L-1 curcumin for 24 h.The expression of CDK4 was significantly up-regulated and GADD45g,BRCA1 were significantly down-regulated.Conclusion Curcumin radiosensitizes nasopharyngeal carcinoma cell line CNE-2R by changing cell cycle and affecting DNA damage repair through regulating the expression of CDK4,GADD45 g and BRCA1.

Objective To optimize the matrix formula of propranolol hydrochloride gels. Methods On the basis of single factor experiment, central composite design-response surface method was used to optimize the formula. Addition levels of glycerol (A), PEG-400 (B) and HPMC (C) were evaluated as the independent variables.Eight-hour accumulative penetration amount per unit area measured by HPLC was used as the index. Quadratic polynomial was used to estimate the relationship between the index and the independent variables, and to delineate response surface and overlay contour plots in order to select the optimal formulations.Finally, predicted responses were verified. Results The optimized formula consisted of 18.53% glycerol, 8.54% PEG-400 and 2.35% HPMC.The quadratic polynomial regression model of 8-h accumulative penetration amount per unit area:R1=-7 415. 69+306. 10A+167. 47B+4 820. 59C-8. 26A2-9. 81B2-1 025. 75C2 , and the cumulative transmittance was 49.6%. Conclusion A credible model is established by using central composite design-response surface method and the formula of propranolol hydrochloride gels is optimized and the gel is stable and controllable.

Objective To investigate the risk factors, diagnostic evaluation, etiology, and treatment in young patients with ischemic stroke. Methods The clinical data of young patients (age range 18 - 45 years) with ischemic stroke (within 2 weeks of stroke onset) admitted to the Stroke Center, the First Affiliated Hospital of Sun Yat-sen University from August 2008 to July 2013 were registered prospectively. Results A total of 300 patients were enroled, their age was 37. 8 ± 6. 8 years. There were 227 males (75. 7% ). The age of 84 patients (28. 0% ) was ≤35 years. The most common risk factors were smoking (43. 3% ), hypertension (38. 7% ), and hypercholesterolemia (38. 0% ). The positive result detection rates were lower in the antinuclear antibody (8/278), anticardiolipin antibody (34/250), 24-h Holter monitoring (2/60 ), and transthoracic echocardiography (38/232). According to the MRI findings, the detection rate of the white matter changes, old infarcts, single acute infarcts, and multiple acute cerebral infarcts were 40/282, 77/282, 145/282, and 137/282, respectively. The stroke subtypes of TOAST: large artery atherosclerosis (26. 7% ), smal artery occlusion (18. 0% ), cardioembolism (10. 0% ), other determined etiology (23. 0% ), and undetermined etiology (22. 3% ). Large artery atherosclerosis was mainly involved in anterior circulation (69/80) and intracranial arteries (75/80). In other definite causes, cerebral artery dissection was most common (36/69), and other causes included moyamoya disease (7/69) and infectious vasculitis (7/69), etc. The average length of hospital stay was 15. 4 d. The mean National Institutes of Health Stroke Scale score on admission was 7. 0, and the mean modified Rankin scale score at discharge was 2. 5. The complication rate during hospitalization was 9. 7% . 80. 3% and 48. 3% of patients received anti-platelet drugs and statins therapy during hospitalization.Conclusions This study used a prospective single-center method. It conducted a comprehensive analysis of risk factors, diagnostic evaluation, treatment, and etiology in current Chinese young patients with ischemic stroke. Its research data wil provide useful information for establishing a diagnostic strategy of high performance cost ratio, in-depth understanding of its pathophysiological mechanisms, and improving treatment strategies in Chinese young patients with ischemic stroke.

Objective To investigate the biological effects of 125I seeds and 60Co γ-rays on the non-small cell lung cancer cells A549 and the normal bronchial epithelium cells BEAS-2B.Methods A549 and BEAS-2B cells were irradiated with 125I seeds and 60Co γ-rays.The survival fraction was detected by colony formation assay.The cell cycle and cell apoptotic ratio were detected by flow cytometry.The expression of cell apoptotic related proteins was examined by western blot.Results After irradiation with different doses,the survival of A549 cells irradiated with 125I seeds was lower than that irradiated with γ-rays (t =6.06,9.42,4.90,P ＜0.05).After irradiation with 4 Gy of 125I seeds and 60Co γ-rays,the G1 phase percentages of A549 cells were 70.67％ ± 1.49％ and 59.59％ ± 0.71％ (t =10.77,P ＜ 0.05),and the apoptotic ratios of A549 cells were 18.09％ ±0.73％ and 9.81％ ±0.16％ (t =19.40,P＜ 0.05),respectively.125I seeds irradiation remarkably up-regulated the expressions of Bax and cleaved Caspase-3 proteins,down-regulated the expression of Bcl-2 proteins compared with 60Co γ-rays irradiation on A549 cells.However,the apoptotic ratio and the expressions of apoptosis-related proteins in BEAS-2B cells had little difference between two types of radiation.Conclusions The anti-proliferative effect of 125I seeds irradiation on A549 cell is more remarkably than that of 60Co γ-rays.The imbalance of Bcl-2/Bax ratio and the eventually activation of Caspase-3 proteins may play an important role in the anti-proliferative effect induced by the continuous low dose radiation of 125I-seeds.

Objective To investigate the values of conventional magnetic resonance imaging (MRI),magnetic resonance angiography (MRA),and high-resolution MRI for diagnosing intracranial arterial dissection (IAD)caused ischemic stroke. Methods From August 2008 to April 2015,59 consecu-tive patients (age 45 ±15years,41males)with IAD caused ischemic stroke admitted to the First Affiliated Hos-pital of Sun Yat-Sen University were enrolled prospectively. All patients underwent conventional cranial MRI/MRA examination,25 of them underwent whole brain DSA examination,and 10 underwent high-resolution MRI. The findings of conventional MRI/ MRA and high-resolution MRI of IAD were analyzed. For patients undergoing DSA,the proportions of detection and compliance of IAD were compared between DSA and conventional MRI / MRA. Results (1)Conventional MRI / MRA revealed typical sign of artery dissection in 42 patients (71. 2%),among them,the intramural hematoma (n = 22,52. 4%)was most common. Other common signs included intimal flap/ double lumen sign (n = 13,31. 0%)and long irregular or thread-like stenosis (n = 9,21. 4%);while dissecting aneurysm (n = 7,16. 7%)and rat tail-shaped occlusion (n = 3, 7. 1%)were relatively rare. In 17 patients (28. 8%)with IAD that conventional MRI/ MRA did not detect the typical dissection sign,the dissections were involved in the middle cerebral artery (11 / 17,64. 7%), they were more common than the 42 patients with IAD (10 / 42,23. 8%)detected the typical dissection sign by conventional MRI/ MRA. There was significant difference (P = 0. 006). (2)Among the 25 patients undergoing DSA,DSA revealed that 15 patients (60%)had the typical dissection sign,and conventional MRI/ MRA only revealed 8 of them (32%)with the typical dissection sign,but there was no significant difference (P = 0. 088). In 15 patients with IAD that DSA detected the typical dissection sign;conventional MRI / MRA detected the typical dissection sign in 8 of them. The diagnostic coincidence rate was 8 / 15. (3)Both conventional MRI/ MRA and DSA revealed non-specific limitation stenosis or cut-off occlusion in 10 patients (16. 9%)with IAD,while the high-resolution MRI revealed intimal flap in 5 of them,intramural hematoma in 4,and intimal flap and intramural hematoma in 1. Conclusion Conventional cranial MRI/MRA is an effective technique for revealing IAD,whereas high-resolution MRI has the unique advantages for diagnosing IAD without typical dissection in other vascular imaging.

Objective Toinvestigatetheriskoflong-termrecurrenceofstrokeanditspredictorsin youngpatientswithischemicstroke/transientischemicattack(TIA).Methods Theclinicaldataofthe consecutive young patients (18-45 years)with ischemic stroke/TIA (within 2 weeks after onset)admitted to the department of neurology in the First Affiliated Hospital of Sun Yat-Sen University between August 2008 and July 2013 were enrolled prospectively. All patients were regularly followed up for a long time (The patients were followed up at the 1 st,6 th,and 12 th month after onset;then they were followed up once for every 6 months)in order to investigate stroke recurrence. The Kaplan-Meier curves were used to analyze the cumulative stroke recurrence rate of all patients. The last contact time for patients lost to follow was used as censored data to be enrolled in the analysis. The univariate analysis of the related risk factors for stroke recurrence using Log-rank test. Multivariate Cox proportional hazard regression was used to detect the related risk factors associated with stroke recurrence (adjusting for age and sex). The variables of the results of Log-ranktestP≤0.1wasselectedandenrolledinthemultivariateregressionanalysis.Results Atotalof 312 patients were enrolled in the analysis,including 294 with ischemic stroke and 18 with TIA. Their mean follow-up time was 34 ± 19 months. Thirty-four patients had recurrent stroke,including 23 with ischemic stroke,7 with TIA,and 4 with cerebral hemorrhage. The cumulative recurrence rates of stroke at 1 ,3 , and 6 years after onset were 6. 2%,10. 3%,and 16. 4%,respectively. The results of multivariate Cox proportional hazards regression analysis showed that hypertension (risk ratio [RR]2. 159;95% confidence interval [CI]1. 048-4. 447,P=0. 037)and cardioembolism (RR,2. 869;95%CI 1. 119-7. 357,P=0.028)weretheindependentpredictorsforstrokerecurrence.Conclusion Theoverall6-yearriskof recurrent stroke is not high in the Chinese young patients with ischemic stroke/TIA,but the risk of stroke recurrence is relatively higher in the first year. Hypertension and cardioembolism are the potential predictors of stroke recurrence;therefore,attention should be paid in clinical practice.

BACKGROUNDLowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.

METHODSIn this multicenter, randomized, double-masked, parallel controlled study, patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments. Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M. The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITT) population. Primary analysis evaluated the non-inferiority of bimatoprost/ timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was ≤ 1.5 mmHg. Adverse events were collected and slit-lamp examinations were performed to assess safety. Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.

RESULTSOf the enrolled 235 patients, 121 patients were randomized to receive bimatoprost/timolol fixed combination and, 114 patients were randomized to receive concurrent treatment. At baseline the mean value of mean diurnal IOP was (25.20 ± 3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87 ± 3.88) mmHg in the concurrent group. The difference between the treatment groups was not statistically significant. The mean change from baseline in mean diurnal IOP (± standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38 ± 4.66) mmHg and it was (-8.93 ± 4.25) mmHg in the concurrent group (P < 0.01). The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68, 0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121) of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the concurrent patients. The most frequent adverse event was conjunctival hyperemia, which was reported as treatment related in 16.5% (20/121) in the bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent group (P > 0.05).

CONCLUSIONSBimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components. Safety profiles were similar between the treatment groups.

Adolescent ; Adult ; Aged ; Amides ; administration & dosage ; adverse effects ; therapeutic use ; Bimatoprost ; Cloprostenol ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Glaucoma, Open-Angle ; drug therapy ; Humans ; Male ; Middle Aged ; Ocular Hypertension ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; therapeutic use ; Young Adult

Objective To compare the outcomes of patients starting peritoneal dialysis (PD)within two weeks and more than two weeks after catheter implantation.Methods All the patients undergoing Tenckhoff catheter implantation and initiating PD in Renji Hospital from January 2001 to December 2010 were enrolled in the study.Patients started PD within 2 weeks after catheter insertion were defined as urgent group,and those started PD 2 weeks later were defined as planned group.Kaplan-Meier curves and Log-rank tests were used to compare outcomes between two groups.Results Among 657 patients in this study,median break-in period was 6 days of 469 (71.4％)patients in urgent group and 26 days of 188 (28.6％) patients in planned group.Compared to planned group,patients of urgent group were younger [(52.6± 17.3) vs (56.1± 15.3) year,P =0.017],had less eGFR [(5.36±2.03) vs (6.50±2.50) ml· min-1 · (1.73 m2)-1,P ＜ 0.01],lower serum albumin [(34.0±5.7) vs (36.2±5.9) g/L,P ＜ 0.01] and hemoglobin [(76.9± 18.8) vs (80.8 ± 17.9) g/L,P =0.018],and higher phosphate [(2.19±0.67) vs (1.98±0.52) mmol/L,P＜ 0.01].Urgent group presented more catheter dysfunctions needed to transfer to hemodialysis (2.1％ vs 0％,P =0.044).The 1-,2-,3-and 5-year technique survival rates of urgent and planned group were 94％ vs 98％,92％ vs 94％,90％ vs 92％and 86％ vs 85％ respectively.There was no significant difference in technique survival (Log-rank =1.536,P =0.22) and peritonitis-free survival (Log-rank =0.035,P =0.85) between two groups.The 1-,2-,3-and 5-year patient survival rates of urgent and planned group were 90％ vs 95％,81％ vs 90％,74％ vs 79％ and 67％ vs 74％ respectively,and no significant difference was found (Log-rank =2.364,P =0.12).Conclusions Although patients needing urgent initial PD have poorer residual renal function and nutritional condition compared to those of planned initial PD,their outcomes are similar.Peritoneal dialysis may be a feasible and safe dialysis modality for patients who need urgent start.