Objective To investigate the effects of stress on the methylation of brain derived neurotrophic factor gene in the patients with major depressive disorder (MDD),and to investigate the relationship between BDNF gene methylation and MDD.Methods 47 cases of MDD were divided into MDD stress group (n=24) and MDD non stress group(n=23) while 27 health subjects were collected as normal control group.The methylation status of CpG island in the promoter region of BDNF gene in peripheral blood was detected by the method of heavy hydrogen and hydrogen sulfate.SPSS17.0 statistical software package was used to analyze the data.The differences of 19 CpG methylation rates and the overall level of methylation rates of three groups were analyzed.Results The CpG overall methylation rates (median,interquartile range) of MDD stress group,MDD non stress group and normal control group was 189.150 (7.575),188.500 (400)and 480.200(770) respectively,and the difference was statistically significant (P＜0.01).There was no significant difference in the overall methylation rate of CpG in the MDD stress group compared with MDD non stress group (P＞0.05).The CpG methylation rates (mean± SD or median,interquartile range) of three groups were detected as follows:CpG-1:2.600(0.275),2.700 (0.400),6.500(0.800);CpG-2:3.350(0.650),3.300(0.800),14.600(1.500);CpG-3:1.596±0.363,1.543±0.400,4.581 ±0.437;CpG-4:1.779±0.516,1.522±0.329,4.033 ±0.529;CpG-5:0.900 (0.575),0.800 (0.600),5.700 (1.500);CpG-6:6.258 ± 0.805,6.213 ±0.944,14.589±0.819;CpG-7:10.667±0.894,10.283± 1.006,15.000±0.763;CpG-8:16.421 ±0.697,16.330±0.775,24.796±0.547;CpG-9:4.713±0.565,4.891 ±0.554,28.826±0.679;CpG-10:10.254±0.902,10.378±0.777,11.381±0.538;CpG-11:24.125±2.301,24.170±2.613,37.474± 1.579;CpG-12:5.442±0.641,5.596±1.117,12.141 ±0.940;CpG-13:4.150(1.150),4.200(1.000),61.700(4.800);CpG-14:5.500±0.544,5.717±0.568,6.378±0.397;CpG-15:3.700 (0.700),4.100(1.000),63.300(2.500);CpG-16:8.200 (1.775),8.100(1.500),75.200(3.300);CpG-17:3.250(0.550),3.300(0.800),34.600(5.000);CpG-18:1.988±0.279,1.939±0.259,2.330±0.207;CpG-19:35.338±2.421,35.187±2.259,65.941 ±2.692.16 CpG methylation rates of 19 CpG were higher in MDD stress group and MDD non stress group.Compared with the normal control group,the difference was statistically significant (P＜0.01).There was no significant difference in CpG methylation rate between MDD stress group and MDD non stress group (P＞0.05).Conclusion The overall methylation rate of CpG in BDNF gene promoter region is closely related with MDD,which may affect the incidence of MDD.There was no correlation between CpG methylation in BDNF gene promoter region and MDD,and stressful life events may not be the direct cause of CpG methylation in BDNF gene promoter region in patients with MDD.

Objective To explore the distribution on-511C/T,-31T/C single nucleotide polymorphism of IL-1β gene among Uygur population in Xinjiang,and to analyze the correlation between IL-1β gene polymorphism and depressive disorders.Methods A total of 100 patients with depressive disorders and 120 control subjects were selected.Polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR),enzyme digestion and sequence reaction were used to detect the common-511C/T,-31T/C polymorphism of the IL-1β gene.The relationship between the polymorphism in the IL-1β gene and the severity of depressive disorders was analyzed.Results The frequencies of CC,CT,TT in-511 were 19.0％,58.0％ and 23.0％ in patient group,while those were 19.2％,55.0％,25.8％ in the control group,which did not show statistically significant differences (x2=0.266,P=0.875).The frequencies of CC,CT,TT in-31 were 24.0％,58.0％ and 18.0％ in the patient group,while those were 24.2％,58.3％,17.5％ in the control group,which did not show statistically significant differences (x2=0.0093,P=0.995).The frequencies of CC,CT,TT genotypes of the IL-1β gene polymorphism (-511 C/T,-31 T/C) were not statistically different between depressive patients and healthy controls.Conclusion The findings suggest no significant association between-511C/T,-31T/C polymorphism and depressive disorders in Uygur population of Xinjiang.

Objective To investigate the action of interlukin-2(IL-2),interlukin-6(IL-6) and its soluble receptors (sIL-2R,sIL-6R) in the first episode of depression in the patients of Uyghur nationality and the differences in IL-2,IL-6 and sIL-2R,sIL-6R levels between the responsive depressed patients and the refractory depressed patients treated with venlafaxine.Methods A case-control study design was conducted.57 first-episode patients with depression (patient group) and 55 healthy people matched with gender and age (control group) were recruited in the study.An intervention with sustained-releasing venlafaxine tablets at fixed dose of 150 mg/d was performed in the patient group.The severity of the illness was evaluated by using the Hamilton's depression scale (HAMD-17) before and after the therapy.And by calculating the reduction rate of HAMD-17 (≥ 50％ or ＜50％),the patients were divided into the responsive or refractory groups.The serum levels of IL-2,IL-6,sIL-2R and sIL-6R in patients and controls were tested by ELISA,and a re-test was done with the patients after treatment.Results There were statistical significant differences of the levels of serum IL-2,IL-6 and sIL-2R,sIL-6R between the patients and the control group (P ＜ 0.01).After treatment,the levels of serum IL-2,IL-6,sIL-2R and sIL-6R in responsive patients were significantly decreased when compared with those before the treatment(P＜ 0.01).The four indexes of refractory patients didn' t alter after venlafaxine treatment (P ＞ 0.05).There were positive correlations between HAMD,serum IL-2 (r =0.677 ; P =0.000) and IL-6 (r =0.197 ; P =0.033) before treatment in all patients.Conclusion Serum IL-2 and IL-6 may play a role in the onset of the depression.The efficacy of venlafaxine is negatively correlated with the levels of serum IL-2 and IL-6.Regulating the imbalanced inflammatory cytokines and the immune system may be one of the mechanisms of drug therapy of depression.

Objective To explore the role of brain derived neurotrophic factor(BDNF) promoter methylation for the morbidity of depression patients,and to investigate the relevance between BDNF promoter methylation and the suicidal ideation in patients with first-episode major depressive disorder.Methods The peripheral blood samples from 23 cases of depression patients with suicide ideation ,24 cases of depression patients without suicide ideation,and 27 healthy controls were grouped using simple randomization method, and the methylation status of CpG island of BDNF promoter were subsequently evaluated using bisulphite sequencing.Results The methylation rates(median,quartile interval) of depression patients with suicidal ideation, depression patients without suicidal attempt, and the healthy control were detected as follows, CPG-1 : 2.60 (0.28), 2.70 (0.60), 6.40 (1.00);CPG-2:3.35 (1.15),3.20 (1.00),14.50 (2.60);CPG-3:1.50 (0.40),1.50 (0.60),4.60 (0.90);CPG-4:1.75 (0.90) ,1.50 (0.50),3.90 (0.90);CPG-5:0.80 (0.58),0.90 (1.00),5.70 (2.10);CPG-6:6.05 (1.03),6.20 (1.70), 14.50 (1.70);CPG-7:10.55 (1.68), 10.10 (1.50), 14.70 (1.70);CPG-8:16.35 (0.90), 16.40 (1.00),4.80 (1.20);CPG-9:4.20 (4.80),4.70 (1.30),28.50 (19.30);CPG-10:10.25 (1.08),10.30 (1.20) ,4.30 (0.90);CPG-11:62.80 (4.05) ,62.30 (4.00) ,37.20 (2.60);CPG-12:5.60 (1.05) ,5.60 (1.30) ,12.30 (1.80);CPG-13:4.15 (1.10) ,4.10 (1.10) ,59.70 (4.90);CPG-14:5.45 (0.78) ,5.70 (0.90),6.30 (0.60);CPG-15:3.70 (0.70) ,3.90 (1.00) ,62.40 (6.50);CPG-16:8.05 (1.75) ,8.10 (1.60) ,74.30 (50.90);CPG-17:3.20 (0.78),3.20 (0.80),32.40 (13.20);CPG-18:1.90 (0.48),1.80 (0.40),2.30 (0.30);CPG-19 : 35.00 (6.27), 35.20 (3.00), 64.20 (44.70).There was an obvious difference in methylation rate among three groups,which was statistically significant (P＜0.01).However, no statistical significance for the methylation rates was observed between the depression patients with suicidal ideation and without suicidal ideation.Interestingly, statistical significance for the methylation rates were observed when compared the depression patients with suicidal ideation with healthy control (P＜ 0.05), and the depression patients without suicidal ideation with healthy control (P＜0.05).Conclusion The results show that the association is observed between BDNF promoter methylation and the morbidity of depressive disorder,but not between BDNF promoter methylation and the suicidal ideation of depression patients.

Spinal edema is a very important pathophysiological basis for secondary spinal cord injury,which affects the repair and prognosis of spinal cord injury.Aquaporin-4 is widely distributed in various organs of the body,and is highly expressed in the brain and spinal cord.Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system.It interacts with aquaporins in function.Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema,inhibition of glial scar formation and promotion of excitotoxic agents exclusion.The distribution and function of aquaporin-4 and inward rectifying potassium channel 4.1 in the central nervous system and their expression after spinal cord injury have multiple effects on spinal edema.Studies of aquaporin-4 and inward rectifying potassium channel 4.1 in the spinal cord may provide new ideas for the elimination and treatment of spinal edema.

Objective To explore the expression and the changes of microtubule, aquaporin-4 (AQP4) and potassium ion channel 4.1 (Kir4.1) after spinal cord injury in rats.Methods Ninety female adult Sprague-Dawley rats were randomly divided into sham operation group (n=30) and injury group (n=60). The injury group was divided into six hours, one day, three days, five days and seven days subgroups, with twelve rats in each subgroup. Spinal cord injury at T10 was established with modified Allen's method (20 g×25 mm) in the injury group. The water content of spinal cord was measured at each time point after injury. Then, the pathology was observed with HE staining, the expression of α-Tubulin, AQP4 and Kir4.1 was detected and analyzed with immunohistochemical staining and Western blotting.Results The water content of the spinal cord was higher in the injured group than in the sham operation group (P<0.05), and was highest on the fifth day. HE staining showed that the gray matter hemorrhage at six hours after injury; one day after injury, the gray matter bled seriously, and neuron swelling was aggravated; three days after injury, the area of gray matter necrosis increased, and the edema phenomenon was obvious; five days and seven days after injury, the gray matter necrosis and the edema phenomenon were more serious. Western blotting and immunohistochemistry showed that the expression of AQP4 gradually increased after injury, and raised at peak on the fifth day; the expression of α-Tubulin and Kir4.1 was similar, and the expression gradually decreased after injury, especially on the fifth day.Conclusion The expression of α-Tubulin and Kir4.1 is similar after spinal cord injury, and is contrary to the expression of AQP4. α-Tubulin, AQP4 and Kir4.1 may be related after injury and may participate in the formation of spinal cord edema.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.