Objective To investigate the expression and significance of elastin and fibulin-5 in anterior vaginal tissue of women with pelvic organ prolapse (POP). Methods Between November 2006 and June 2008, 68 patients with POP underwent surgical treatment in Shengjing Hospital of China Medical University were enrolled in this study, who were classified into 10 patients with grade Ⅰ , 21 patients with grade Ⅱ , 25 patients with grade Ⅲ and 12 patients with grade Ⅳ in accordance with pelvic organ prolapse quantitation (POP-Q). Meanwhile, 18 cases with early cervical cancer at stage of Ⅰ b were treated by total hysterectomy and bilateral salpingo-oophorectomy, their anterior vaginal tissues were selected as controls. Immunohistochemical staining was performed to detect the expression of elastin and fibulin-5. Results (1 ) Elastin and fibulin-5 were mainly expressed at extracellular matrix(ECM). (2)The positive rate of fibulin-5 expression in anterior vaginal wall were 5% (2/37 ) in grade Ⅲ/Ⅳ and 26% (8/31 ) in grade Ⅰ/Ⅱ POP patients, which reached statistical difference (P = 0. 035). However, no statistical different expression was found between postmenopausal (13%, 8/60) and non-menopausal patients (2/8), vaginal delivery ≤ 2 (19%, 5/27 ) and ＞ 2 patients (12%, 5/41, P ＞ 0. 05 ). (3 ) The positive rate of elastin expression in anterior vaginal wall in POP group was 31% (21/68), which was significantly lower than 72% (13/18) of control group (P = 0. 002). Among POP group, 19% (7/37) of elastin expression in grade Ⅲ/Ⅳ POP was significantly lower than 45% (14/31 ) in grade Ⅰ/Ⅱ of POP patients. However, no statistical difference was found between postmenopausal (30%, 18/60 ) and non-menopausal patients (3/8 ), vaginal delivery ≤ 2 (26%, 7/27) and ＞2 patients(34%, 14/41, P＞0. 05). (4)In POP group, both positive expression of fibulin-5 and elastin of anterior vaginal wall was in 6 cases, both negative expression of fibulin-5 and elastin was in 43 cases. It was illustrated that elastin and fibulin-5 had an positive relationship (P = 0. 031 ). Conclusion The decreased expression of elastin and fibolin-5 was correlated with degree of POP, which indicated that elastin and fibulin-5 may play a role in the pathogenesis of POP.

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Objective: To establish a novel stress-induced depression model by changing the lighting conditions and continuously damping cushion (L-D). Methods: The L-D stress depression animal model was established in C57BL / 6 mice with body weight of 18-22 g. Seventy-five mice with the horizontal and vertical scores higher than 30 and less than 120 in open field test were employed.In the research of model construction, mice were randomly divided into three groups: control group (n=9), chronic unpredictable mild stress(CUMS) model group (n=10) and L-D model group (n=9). In the drug intervention experiments, mice were randomly divided into five groups: control group (n=9), chronic unpredictable mild stress(CUMS) model group (n=10), L-D model group (n=9), CUMS+ fluoxetine group (n=10) and L-D model+ fluoxetine group (n=9). Open field test, forced swimming test and sucrose preference test were used to evaluate the degree of depression in animals. Results: (1) In the open field test, the horizontal score of CUMS model group (67.20±5.81) and the L-D model group (52.56±19.05) were significantly lower than that of the control group (76.44±9.22) (t=2.645, t=3.387, both P<0.05). And horizontal score of the L-D model was significantly lower than that of the CUMS model (t=2.321, both P<0.05). In forced swimming experiment, compared with the control group ((39.67±21.12)s), the immobility time of the CUMS model group ((60.90±10.34)s) and the L-D model group ((74.89±16.10)s) were significantly prolonged (t=2.831, 3.979, both P<0.05). The immobility time of the L-D model group was also significantly higher than that of the CUMS model group (t=2.278, P<0.05). In the sucrose preference experiment, the percentage of sucrose preference in CUMS model group ((72±7)%) and L-D model group ((65±5)%) was lower than that in the control group ((81±12)%) (t=2.195, 3.875, both P<0.05). The percentage of sucrose preference of L-D model group was significantly higher than that of CUMS model group (t=2.286, P<0.05). (2) After intervention with antidepressants, the horizontal scores of the CUMS model group (65.60±6.43) and the L-D model group (54.33±14.67) were significantly lower than that of the control group (75.78±8.27) in open field test (t=3.011, t=3.861, both P<0.05), and the score of L-D group was lower than that of CUMS group(t=2.235, P<0.05). The vertical score of the L-D model group (33.44±4.54) was significantly lower than that of the control group (39.22±5.56) (t=2.553, P<0.05). There was significant increase in the level score and vertical score of CUMS model and L-D model after fluoxetine intervention (t=3.090, t=2.692, both P<0.05), and significant twist in the vertical score of CUMS model and L-D model (t=2.681, t=2.354; both P<0.05). In the forced swimming experiment, the immobility time of the L-D model((64.11±13.06)s) was significantly longer than that of the control group ((42.00±13.77)s) (t=3.494, P<0.05). The immobility time of CUMS model and L-D model mice was significantly longer than that of non-intervention group (t=2.137, 2.940, both P<0.05). After the intervention of fluoxetine, there was no significant difference between the CUMS group, L-D group, the control group(all P>0.05). Conclusion Changing the lighting conditions and continuously damping cushion is a new method to establish mice model with depression behavior.Shorter modeling duration and simple operation are the main advantages of this model.