BACKGROUND: As the damage caused by protein glycation is one of the mechanisms of diabetes, it is helpful to treat diabetes related diseases with the understanding of the inhibition of berberine on protein glycation and the protection to the brain damage caused by protein glycation.OBJECTIVE: To observe the effects of berberine on glycated brain damages induced by D-galactose in model rats.DESIGN: Randomly grouping paralleled control study.SETTING: Department of Ophthalmology, Xiamen Traditional Chinese Medicine Hospital.MATERIALS: The experiment was conducted in the Department of Pharmacology, Pharmacy College of Jinan University from June to October 2005. Ninety SD rats (6 weeks old) were selected and divided into 6 groups: control group, model group, hydrochloride aminoguanidine group and high (300 mg/kg), middle (150 mg/kg) and low (75 mg/kg) doses berberine groups with 15 rats in each group. The glycated models were established by intraperitoneal injection of D-galactose. The main drugs:berberine was from Guangzhou Wanji Drugs Limited Company; D-galactose was from Shanghai Yuanju Bioscience Technology Limited Company.METHODS: The rats in the control group were intraperitoneally injected the normal saline for 8 weeks; rats in other groups were injected 5%D-galactose (150 mg/kg) for 8 weeks. From the 3rd week, the hydrochloride aminoguanidine group was infused hydrochloride aminoganidine (150 mg/kg); the three doses berberine groups were given corresponding doses berberine; the control group and model group were given distilled water for 6 weeks with the volume of 10 mL/kg. At the end of the 8th week, the erythrocyte aldose reductase activity was determined by coomassie brilliant blue method; the level of plasma glycohemoglobin was measured by thio-barbituric acid colorimetry and the fructosamine in serum was measured by nitroblue tetrazolium colorimetry. The quantity of advanced glycation end products (AGEs) in serum, and AGEs, malondialdehyde (MDA), and activity of superoxide edismutase (SOD) in brain tissue and calcium ion in neurons were also dertermined. Moreover, the changes of mitochondria in brain hippocampus cells were observed under electronic microscope.MAIN OUTCOME MEASURES: ① The AGEs, plasma glycohemoglobin, serum fructosamine and aldose reductase activity. ②AGEs in brain tissues. ③Calcium level in brain. ④MDA content and SOD activity in brain tissues. ⑤Changes of mitochondria in hippocampus neurons.RESULTS: All 90 animals were involved in the result analysis. ①Aldose reductase activity and glycated product content in serum: After the rats were treated with D-galactose for 8 weeks, the aldose reductase activity in red blood cells and the content of fructosamine in serum, glycohemoglobin,AGEs in the model group were significantly higher than those in the normal control group (P ＜ 0.01); After treated by high and middle doses berberine for 6 weeks, the activity of aldose reductase and content of fructosamine in serum (absorbancevalue of hemoglobin every 10 g), glycohemoglobin, and AGEs were obviously lower than those in the control group [(1.07±0.39), (1.22±0.47), (1.76±0.30) nkat/g, t=5.052, 5.484, P ＜ 0.01;(0.740±0.142), (0.862±0.131), (0.958±0.083) mmol/L, t=7.829, P ＜ 0.01,t=2.404, P ＜ 0.05; 58.434±12.135, 64.614±13.418, 83.747±7.990,t=4.922, 6.748, P ＜ 0.01; (3.104±0.814), (2.937±0.514), (4.156±0.860) U/mg,t=4.104, 3.440, P ＜ 0.05]; the aldose reductase activity of the low dose berberine group was lower than the model group (P ＜ 0.05), which had no obvious effect on glycated products. ②AGEs in brain tissues: The contents in the hydrochloride aminoganidine group, high and middle doses berberine groups were lower than the model group [(10.52±1.22), (10.95±1.75),(11.95±2.27), (14.26±3.51) U/mg, t=-3.892, -3.263, P ＜ 0.01, t=-2.139,P ＜ 0.05], and the low dose berberine had little effect (P ＞ 0.05). ③Calcium level in neurons: The levels in the hydrochloride aminoganidine group,and high dose berberine groups were lower than the model group.[(271.52±32.71), (293.84±31.58), (337.15±58.49) nmol/L, t=-3.421, P＜ 0.01, t=-2.275, P ＜ 0.05], the low dose berberine group had no obvious effect (P ＞ 0.05). ④MDA content and SOD activity in brain tissues: MDA contents in the hydrochloride aminoganidine group, high and middle doses berberine groups were lower than the model group, and the SOD activity was markedly higher than the model group [(2.09±0.16), (2.12±0.22),(2.41±0.12), (2.54±0.21) μmol/g, t=6.601, 5.348, P ＜ 0.01, t=2.082, P＜ 0.05; (8.79±1.09), (8.80±1.52), (7.90±1.48), (6.48±1.34) mkat/g, t=4.571,4.254, P ＜ 0.01, t=2.226, P ＜ 0.05]. ⑤Mitochondria structure in brain hippocampus cells: Under the electronic microscope, mitochondria in brain hippocampus cells of the model group appeared obvious swelling with broken crests and disorganized structure, even obvious big vacuoles were observed. In the hydrochloride aminoganidine, and high and middle doses berberine groups, no obvious swelling was observed with vacuoles only in a few mitochondria. Nevertheless, obvious swelling appeared in mitochondria of low dose berberine group with broken crest and disorganized structure,and vacuoles were observed.CONCLUSION: D-galactose-induced damage in mitochondria may be related to AGEs formation in brain tissue, maladjustment of calcium ions in neurons and oxidative stress in rat models. Berberine can inhibit glycation induced by D-galactose and protect rat brain tissues from glycated damage.

Objective To assess the reflectance confocal microscopic features of childhood lichen planus (LP),and to evaluate the performance of reflectance confocal microscopy (RCM) in the diagnosis of childhood LP.Methods RCM was performed for imaging of lesions in 35 children with LP.Then,biopsies were carried out at the same sites followed by histopathological examination.A comparison was conducted between confocal microscopic and histopathological findings.All the 35 cases were diagnosed based on clinical manifestations and histopathological findings.Results RCM imaging of lesions in the 35 cases showed cellular edema forming lowly reflective areas in the epidermis,sharp transition between the granular and spinous layers,and infiltration of moderately reflective inflammatory cells,which corresponded to wedge-shaped thickening of the granular layer on pathological examination.The dermo-epidermal junction was unclear,and dermal papillary rings were obscure or absent with infiltration of inflammatory cells arranged in lamelliform structures around the dermo-epidermal junction,which corresponded to interface dermatitis on histopathological examination.A band-like infiltration of inflammatory cells,including big,highly reflective oval or stelliform pigmentophages and small,moderately reflective round lymphocytes,was observed in the dermis,and the thickness of infiltration was measurable.Dilated blood vessels were longitudinally distributed in the papillary dermis with perivascular infiltration of inflammatory cells and pigmentophages.RCM images were highly consistent with histopathological findings in these patients.Conclusion RCM,as a real-time non-invasive imaging technique,can serve as an auxiliary examination method for the diagnosis of childhood LP.

The individuality of mangrove ecotope determined the diversity and specificity of symbiotic microorganisms and their metabolites. However, being confined by the knowledge and cultivation means, the field on mangrove symbiotic microorganisms was on starting. In this paper, the progresses on symbiotic microorganisms of mangrove were reviewed, which hint the essentiality and trends of that field.

To investigate the potential risk factors for parotid gland failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).Methods The clinical data of 1096 NPC patients who underwent IMRT in our hospital from January 2005 to December 2012 were analyzed retrospectively.Among these patients, 13 patients experienced parotid gland recurrence, and the recurrence in 12 patients was analyzed.A case-control study was performed with the side of the parotid gland with recurrence as the case group and the side of the parotid gland without recurrence as the control group.The association of parotid gland failure with the extent of tumor invasion, IMRT dose distribution, and local recurrence was analyzed.The differences between groups were analyzed with χ2 test or Fisher′s the exact probability test.Results Among the 12 patients, 11 had stage III-IV primary NPC;after definitive IMRT, 9 had local tumor residues.The median time of parotid gland recurrence was 16(8-43) months.Of all the patients who experienced recurrence, 8 had recurrence in the superficial lobe of the parotid gland, 1 in the deep lobe, and 3 in both superficial and deep lobes.Recurrence was in the same side of primary tumor (P<0.001).Compared with the controls, the side of the parotid gland with recurrence had higher rate of cervical puncture/surgery (P=0.025).Parotid gland recurrence was often complicated by ipsilateral lymph node recurrence (67% vs.8%, P=0.003), as well as the tendency of ipsilateral primary lesion recurrence (42%vs.8%;P=0.059).Conclusions For NPC patients, the recurrence rate in the parotid gland is very low. Parotid gland recurrence may be related to locally advanced NPC, residues after treatment, the history of cervical puncture/surgery, and locoregional recurrence.The low radiotherapy dose in the parotid gland caused by IMRT may be an important reason for parotid gland recurrence.

Objective To investigate the treatment outcome of primary mucosal melanoma of the nasal cavity and paranasal sinuses and the role of radiotherapy in the treatment of this disease .Methods The clinical data of 52 patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses who were admitted to our hospital from 2001 to 2014 were analyzed retrospectively.Among these patients, 18 received surgery alone, 31 received surgery combined with radiotherapy ( 24 received surgery and postoperative radiotherapy and 7 received preoperative radiotherapy and surgery ) , and 3 received radiotherapy alone.The surgery+radiotherapy group and the surgery group were matched using propensity score matching.Results The median follow-up was 59 months.The 5-year local control ( LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of all patients were 49%, 48%, 22%, and 45%, respectively.After matching, the surgery+radiotherapy group had a significantly higher LC than the surgery group (88%vs.43%, P=0.028), but the two groups had similar 5-year DMFS (67%vs.57%, P=0.955), 5-year DFS (58%vs.24%, P=0.131), and 5-year OS (67%vs. 67%, P=0.727 ) .The negative margin rates in the preoperative radiotherapy+surgery subgroup and the surgery+postoperative radiotherapy subgroup were 100%and 50%, respectively ( P=0.004) .Conclusions Surgery combined with radiotherapy can improve the LC rate in patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses, and preoperative radiotherapy can increase the negative margin rate.

Objective To analyze the treatment outcomes of patients with primary sphenoid sinus malignancies. Methods Sixteen patients with primary sphenoid sinus malignancies admitted to our hospital from 2000 to 2013 were analyzed retrospectively. No patients were newly diagnosed with cervical lymph node metastasis. One patient had stageⅣA disease, while fifteen had stageⅣB disease. Eleven patients received surgery followed by radiotherapy, one surgery alone, three radiotherapy alone, and one chemotherapy alone. All surgeries were cytoreductive . The median dose of radiotherapy was 69. 96 Gy ( 56.00?80. 56 Gy ) . Results The 3?year local control ( LC) , distant metastasis?free survival ( DMFS) , disease?free survival ( DFS) , and disease?specific survival ( DSS) rates were 67%, 69%, 44%, and 58%, respectively, in all patients, and 67%, 55%, 30%, and 41%, respectively, in patients treated with cytoreductive surgery followed by radiotherapy. All orbital contents and skull base were preserved. In all patients, the local recurrence, distant metastasis, and lymph node recurrence rates were 25%, 37%, and 6%, respectively. There were no independent predictors for the LC and DSS rates based on the prognostic analysis. Conclusions With the orbital contents and skull base preserved, the cytoreductive surgery followed by radiotherapy yields satisfactory outcomes and a low lymph node recurrence rate in the treatment of sphenoid sinus malignancies. The prophylactic irradiation of cervical lymph nodes is not recommended in clinical practice.

Objective To detect the change of exoression level of plasma microRNA‐21(miR‐21) and TGF‐β1 in cardiac remode‐lin affer acute myocardial infarction(AMI) of the pateins .Methods 200 pateints with AMI and 100 normal controls(age ,sex matched) were enrolled .Blood samples were obtained from the normal controls and patients with AMI on the 3 days ,7 days and 14 days .Real‐time PCR was developed to detect the expression of miR‐21 and TGF‐β1 in plasma .Results The expression of miR‐21 was significantly up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .74 ± 0 .21 vs .2 .62 ± 0 .23 , vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .98 ± 0 .18 vs .2 .35 ± 0 .24 ,vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 ,P<0 .05 ,respectively .The expression of miR‐21 and TGF‐β1 were up‐regulation with the change of cardiac function .Positive relationship between miRNA‐21 expression and LVDd (r=0 .757 ,P<0 .05);Positive relationship between TGF‐β1 mRNA expression and LVDd(r=0 .701 ,P<0 .05) .Conclusion The expression of miR‐21 and TGF‐β1 were up‐regulation in cardiac remodelin affer AMI of the pateins ,which involved in regulation in cardiac remodelin affer AMI .

Objective To summarize the long term outcomes and prognostic factors of nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy.MethodsFrom Nov 2001to Dec 2009,totally 416 newly diagnosed NPC patients was treated in our hospital.The prescribed dose was 70-78 Gy to the gross tumor volume and 70 Gy to the positive neck nodes,60 Gy to the clinical target volume,and 50-56 Gy to the clinically negative neck.Among 333 stage Ⅲ/Ⅳ patients according to the 2010 UICC staging system,187 received concurrent chemoradiotherapy with a regimen of weekly cisplatin 30mg/m2.Local control rate (LC),overall survival (OS),disease-hree survival (DFS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method.ResultsThe follow up rate is 98.0％.158 patients was followed up more than 5 years.The 5 years LC,OS,DFS and DMFS of whole group were 87.7％,82.1％,71.8％ and 84.5％.Sex,Age,T stage and N stage were independent prognostic factors for OS (x2=4.59,11.20,19.40,18.00,P=0.03,0.00,0.00,0.00),T and N stage were independent prognostic factors for DFS (x2=33.50,21.20,P=0.00,0.00) and DMFS (x2=11.90,14.60,P=0.01,0.01).The 5 years LC,OS,DFS and DMFS for local-regional advanced disease with or without concurrent chemotherapy was 82.2％ and 90.7％ (x2=1.72,P=0.19),70.2％ and 83.4％ (x2=1.42,P=0.23),62.8％ and 73.2％ (x2=2.83,P=0.09),78.0％ and 83.2％ (x2=0.37,P=0.55)respectively.Conclusions The long term outcomes of nasopharyngeal carcinoma treated by intensitymodulated radiotherapy was encouraged.The role of concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma treated by intensity-modulated radiotherapy needs further investigated.

ObjectiveTo investigate the role of chemoradiotherapy in the preoperative radiotherapy for locally advanced head and neck squamous cell carcinoma. MethodsFrom Sep. 2002 to Dec. 2008,totally 157 locally advanced head and neck squamous cell carcinoma (HNSCC) patients was assigned to preoperative concurrent chemoradiotherapy group ( n =81 ) or preoperative radiotherapy alone group ( n =76 ) randomly. The chemotherapy regimen was consisted of cisplatin 30 mg/m2, weekly. The radiotherapy in both groups was identical. The primary lesion will continue concurrent chemoradiotherapy or radiotherapy for those the tumor response was or nearly complete remission (CR) and those who refused surgery when evaluated at DT50 Gy, the others will receive surgery 1 month later if the tumor response was less than CR.For N3 patients, the planed neck dissection will be done. ResultsThe follow up rate was 98. 1％, 91patients followed up more than 5 years, there were 46 in concurrent chemoradiotherapy group and 45 in radiotherapy alone group. The rate of 5-year local control, overall survival, disease free survival and distant metastasis-free survival for preoperative concurrent chemoradiotherapy group and preoperative radiotherapy alone group were 63％ and 50％ ( x2 =0. 40,P =0. 528), 46％ and 38％ ( x2 =0. 48,P =0. 490) ,41％ and 35 ( x2 =0. 29, P =0. 593 ) ,76％ and 65％ ( x2 =3.38, P =0. 066 ) respectively. Subgroup analysis showed that the 2-years distant metastasis-free survival of preoperative concurrent chemoradiotherapy group and preoperative radiotherapy alone group were 88％ and 60％ ( x2 =5.99,P =0. 014). ConclusionsPreoper -ative concurrent chemoraidotherapy with the regimen of cisplatin 30 mg/m2 weekly did not improve the overall survival for locally advanced HNSCCwhen compared with preoperative radiotherapy alone.Preoperative concurrent chemoradiotherapy improved the distant metastasis-free survival of locally advanced hypopharyngeal and laryngeal carcinoma.

Objective To evaluate the clinical characteristics,outcome and prognostic factom of adolescent nasopharyngeal carcinoma.Methods Between Jan 1990 and Dec 2009,totally 148 pathological confirmed nasopharyngeal carcinoma(NPC)patients with age≤20 years were treated in our hospital,including stage Ⅱ 8,stage Ⅲ 58,stage Ⅳ 81,and unknown 1 when restaged by TNM system(UICC 2002),ninty-four(63.5%)patients were treated with radiotherapy alone,54(36.5%)patients were treated with radiotherapy combined with cisplatin-based chemotherapy.Results The median follow-up time for all patients was 44.5 months.The 5-year overall survival(OS),local-regional control(LRC)and distant metastasis-free survival(DMFS)rateswere 82.9%,85.1%and 78.6%.There were 42 patients(28.4%)failed with 16 regional recurrence and 29 distant metastasis,and 3 with both;bone metastasis was the most common site of distant metastasis(22/29).In univariate analysis,the adverse prognostic factors for OS were stage T4(X2=5.61,P=0.018),radiation dose<70 Gy(X2=5.30,P=0.021),for LRC was radiation dose<70 Gy and for distant metastasis-free survival was the disease history≥6month(X2=4.24,P=0.039).In multivariate analysis,radiation dose<70 Gy and stage T4 were the independent prognostic factors for OS(X2=5.73、5.56,P=0.017、0.018),for LRC was radiation dose<70 Gy(X2=5.81,P=0.016).Conclusions The outcome of the present series was excellent,total nagopharyngeal radiation dose less than 70 Gy is inappropriate.Reduce the distant metastasis and late toxicities were the future direction for the treatment of adolescent nasopharyngeal carcinoma.