ObjectiveTo explore the effects of social isolation on the cognition and expression of 5-HT2C receptor(5-HT2CR) and adenosine deaminase that act on RNA 1(ADAR1) in BALB/c mice.MethodsThe healthy BALB/c mice were isolated for 2,4,and 8 weeks individually since postnatal 21 days respectively to set up isolation mice model,the same age mice without isolation were regarded as control group.The new object location and the new object recognition tests were used to measure the spatial and non-spatial cognitive function,and western blot was used to measure the protein expression of 5-HT2CR and ADAR1.ResultsThe new object location test showed that the spatial discrimination index (DI) of BALB/c mice isolated for 2 weeks was decreased significantly compared with the control group(control group was (0.075±0.340),isolation group was (-0.653±0.308),P<0.05),and no obvious difference was found for the group isolated for 4 and 8 weeks.The new object recognition test showed that the non-spatial DI of BALB/c mice isolated for 2 and 4 weeks were decreased significantly compared with the control group(control 2 weeks group was (0.088±0.210),isolation 2 weeks group was (-0.945±0.194),P<0.05;control 4 weeks group was (0.105±0.267),isolation 4 weeks group was (-0.506±0.215),P<0.05),and no obvious difference was found for the group isolated for 8 weeks.Compared with the control group the expression of 5-HT2CR and ADAR1 in the hippocampus were decreased significantly for the group isolated for 2 weeks.(5-HT2CR:control group was (1.025±0.144),isolation group was (0.891±0.026),P<0.05.ADAR1: control group was (0.839±0.120),isolation group was (0.629±0.094),P<0.05).ConclusionsTwo week social isolation results in the decrease of spatial and non-spatial cognitive function in BALB/c mice,in the meanwhile,social isolation stress results in the obvious decrease of 5-HT2C receptor and ADAR1 protein expression in the hippocampus of BALB/c mice.

Objective To explore the effect of depression on loneliness in medical students',and the mediating effects of introverted personality and social support.Methods EPQ,UCLA,SSRS,and POMS questionnaire were used,and surveyed data was collected from Dalian Medical University medical students.Results The scores of depressive mood,introverted personality,social support and loneliness were (17.77±4.45),(11.97±5.21),(34.52±6.15) and (38.02±6.36).Depression was positively related to loneliness and introverted personality (r=0.286,0.508,P＜0.01),and social support was negatively related to loneliness (r =-0.443,P＜0.01).Introverted personality was positively related to loneliness(r=0.401,P＜0.01).The total effect value was 0.670.The mediating effect of introversion as mediator variable was 0.221,accounting for 33％ of the total effect.Social support as intermediary variable,intermediary effect value was 0.449,accounting for 67％ of the total effect.Standard value of mediating effect between depression and introverted personality showed as 0.508 (95％CI=0.475-0.725,P＜0.0i),standard value of mediating effect between depression and social support showed as-0.150 (95％CI=0.989-1.469,P＜0.01),introverted personality was the mediating variant of depression and loneliness,standard value of mediating effect was 0.156 (95％ CI=0.080-0.232,P＜0.01),social support was the mediating variant of depression and loneliness,standard value of mediating effect was 0.317 (95％ CI=0.177-0.457,P＜0.01).Conclusions Introverted personality and social support play an intermediary role between depression and loneliness.

Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice.Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group,the gregarious control group (GH),social isolation model group (SI),ADAR1 inducer treated gregarious group (GH+IFN-γ),ADAR1 inhibitor treated gregarious group (GH+EHNA),ADAR1 inducer treated isolation group (SI+IFN-γ) and ADAR1 inhibitor treated isolation group (SI+EHNA).Mice in drug treatment groups were treated with ADAR1 inducer (5.0? 104 U/kg,20 ml/kg,ip) and inhibitor (10 mg/kg,20 ml/kg,ip).Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADARI immunoreactivity and Western blotwas used to measure ADAR1 protein expression.Results In the objection recognition test,the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41 ±0.17,P＜0.01),the non-spatial discrimination index of mice in SI+IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P＜0.01) and lower (P＜0.05) than that of the SI group respectively.The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus:(0.013±0.003),CAI:(0.021±0.005)) decreased significantly compared to those of GH group(Hilus:(0.021 ±0.002),(0.047±0.004);both P＜0.05).And GH+IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus ((0.013±0.003) vs (0.023±0.004),P＜0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005),P＜0.01) compared with that of SI group,ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48 ±0.07) in hippocampus was significantly decreased (P＜0.01) compared to that of GH group (1.00 ±0.00).The level of ADAR1 protein in SI+IFN-γgroup(0.82 ±0.04) increased compared with that of SI group.Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus.The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively.The related mechanisms may be related to the expression of ADAR1.

Objective:To investigate the safety and effectiveness of tension adjustment technique using anatomical landmarks during retropubic midurethral synthetic sling.Methods:The data of 36 consecutive female patients with urinary incontinence, who had underwent retropubic midurethral synthetic sling procedure from January to August 2019 were analyzed retrospectively. The mean age was (60.83±7.93) years old and the body mass index was (24.43±2.44) kg/m 2. Among the recruited subjects, 36 had positive stress test and Marshall-Marchetti test. 20 (55.6%) were pure stress urinary incontinence, and 16 (44.4%) were mixed urinary incontinence. The severity of incontinence was classified into mild (5 cases, 13.9%), moderate (14 cases, 38.9%), severe (13 cases, 36.1%) and very severe (4 cases, 11.1%) using one-hour pad tests. Urodynamics were performed in 17 cases, with 5 (29.4%) presented detrusor overactivity, 3 (17.7%) possessed intrinsic sphincter deficiency. For each case, the tension of the sling was adjusted based on the anatomical landmarks, i. e. using an angled clamp attached closely to the pubic symphysis ventrally and the tip parallel to the edge of hymen dorsally. All patients were catheter-free right after the procedure. The subjective and objective effectiveness, and safety (the rate of urinary retension after surgery and postvoid residual volume 3 months later) were evaluated.The subjective cure rate was was defined as complete leakage free or very mild leakage during excessive bladder filling and fierce cough. The subjective effectiveness was defined as over 50% improvement of the leakage symptom. The objective cure rate was defined as a negative stress test. Results:For all 36 patients, the median hospital stays was 8 (5-95)h. No bladder perforation or transfusion cases. All patients were catheter-free right after the procedure, with no incidence of urinary retention. 27 patients completed a 3-month follow-up, with 22 had post-void residual data, 23 had subjective effectiveness data and 23 had objective effectiveness data. The median post-void residual was 7.5 (5-64) ml, subjective cure rate was 91.3% (21/23), and objective cure rate was 95.7% (22/23). 8.7% (2/23) reported difficult urination alleviated without the necessity of clinical interference. No urethra erosion or vagina extrusion was found. At 2-year follow-up, 34 patients completed assessment by phone. The subjective cure rate was 91.2% (31/34), with only 2.9% (1/34) reported difficult urination. Besides, at 3-month follow-up, there was no difference regarding the subjective cure rate [100.0%(12/12) vs. 81.8%(9/11)]or objective cure rate [91.7%(11/12) vs. 100.0%(11/11)] between patients with stress and mixed incontinence. No difference was noted among patients with mild, moderate, severe and very severe leakage[75.0% (3/4) vs. 100.0%(6/6) vs. 90.0%(9/10) vs. 100.0%(3/3)]. Of the 12 cases with urodynamic records, the presence of detrusor overactivity [66.7%(2/3) vs. 88.9%(8/9)] or intrinsic sphincter deficiency [0(0/1) vs. 90.9%(10/11)] did not significantly affected the cure rate of the procedure. At 2-year follow-up, there was no difference regarding the subjective cure rate between patients with stress and mixed incontinence [94.7%(18/19) vs. 86.7%(13/15)]. No difference was also noted among patients with mild, moderate, severe and very severe leakage[80.0%(4/5) vs. 100.0%(13/13) vs. 83.3%(10/12) vs. 100.0%(4/4)]. Of the 16 cases with urodynamic records, the presence of detrusor overactivity [60.0%(3/5) vs. 90.9%(10/11)]or intrinsic sphincter deficiency [66.7%(2/3) vs. 84.6%(11/13)]did not significantly affected the cure rate of the procedure.Conclusions:Tension adjustment using anatomic landmarks during sling procedure is safe and feasible for urinary incontinence, with minimum complications and residual volume, and high subjective/objective cure rate.

Objective:To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice.Methods:Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×10 4 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results:The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group ( t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group ( t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice ( t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group ( t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group ( t=3.02, 4.401; P<0.05). Conclusion:ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice.

Objective:To discover the clinical features of nocturnal enuresis (NE) in adults and to detect factors that correlated with the symptom severity.Methods:This cross-sectional study recruited NE subjects from September 2017 through December 2020. All patients had experienced enuresis at least once per week and with a symptom duration of 3 months or longer. Followed by documentation of history and medical records, three-day bladder diary was adopted to assess their voiding pattern, and urodynamic parameters were obtained to evaluate lower urinary tract function.Results:A total of 106 NE patients (43 male and 63 female) were identified. There is no statistical difference regarding the average age (men: 57.8±15.6 vs. women: 56.1±14.0, P>0.05) and BMI (men: 23.9±3.4 vs. women: 23.3±4.3, P>0.05) between men and women. Comorbidities are extremely common in NE patients (n=85, 80.2%), with the incidence rate higher in men compared to women [88.4% (38/43)vs. 74.6% (47/63), P<0.05]. Hypertension (n=58, 54.7%), hyperlipemia (n=41, 38.7%), diabetes mellitus (n=38, 35.8%), coronary heart disease (n=22, 20.8%) were the most frequently reported conditions. On bladder diaries, subjects were frequently manifested nocturnal polyuria (NP, 47/106, 44.3%), reduced nocturnal bladder capacity (NBC, 74/106, 69.8%), or combination of both(33/106, 31.3%). Urodynamic studies suggested that the incidence of reduce bladder compliance, detrusor overactivity (DO), stress incontinence, bladder outlet obstruction(BOO), detrusor underactivity(DU)and detrusor hyperreflexia with impaired contractility(DHIC)was 27.4%(29/106), 39.6%(42/106), 17.9%(19/106), 9.4%(10/106), 25.5%(27/106)and 15.1%(16/106), respectively. Women were more likely to suffer from stress urinary incontinence [2.3%(1/43) men vs. 28.6% (18/63) women, P<0.01], while men were prone to have bladder outlet obstruction [ 23.3%(10/43) men vs. 0 women, P<0.01]. Correlation analysis demonstrated that obesity( r=0.63, P<0.01), systemic comorbidities( r=0.40, P<0.01), presence of NP( r=0.50, P<0.01) and NP+ NBC( r=0.47, P<0.01), post-void residual( r=0.53, P<0.01), reduced compliance( r=0.21, P=0.04), DU( r=0.28, P<0.01), stress incontinence( r=0.42, P<0.01)and DHIC ( r=0.35, P<0.01)are positively correlated with NE severity. Whereas, reduced Q max( r=-0.35, P<0.01), low capacity( r=0.21, P=0.03), and reduced bladder sensation( r=-0.21, P=0.03) correlate negatively with NE severity. Conclusions:The presence of NE is not only a sign of bladder dysfunction, but also an implication of obesity, systematic chronic diseases, urine production malfunctioning. Therefore, a thorough history regarding the lower urinary tract function and systemic comorbidities should be taken carefully, so that, an integrated and personalized treatment can be carried out.

BACKGROUND:Magnetically responsive hydrogels have great advantages in bone tissue engineering,which is more conducive to the minimally invasive and efficient promotion of osteogenesis. OBJECTIVE:To review the application advances of magnetically responsive hydrogels in bone tissue engineering. METHODS:PubMed,Web of Science,WanFang and CNKI databases were used to search relevant literature.The English search terms were"Magnetic Hydrogels,Magnetic Nanoparticles,Superparamagnetic Nanoparticles,Fe3O4,SPIONs,Magnetic Fields,Bone Regeneration,Bone Repair,Bone Tissue Engineering".The Chinese search terms were"Magnetic Hydrogel,Magnetic Nanoparticles,Superparamagnetic Iron Oxide Nanoparticles,Magnetic Field,Iron Oxide Nanoparticles,Bone Regeneration,Bone Reconstruction,Bone Repair,Bone Tissue Engineering".After preliminary screening of all articles according to the inclusion and exclusion criteria,60 articles were finally retained for review. RESULTS AND CONCLUSION:(1)In recent years,due to the emergence of magnetic nanoparticles,more and more magnetic responsive scaffold materials have been developed.Among them,magnetic responsive hydrogels containing iron oxide nanoparticles and superparamagnetic iron oxide nanoparticles have outstanding mechanical properties and good biocompatibility.It can quickly respond to the external magnetic field and provide the magnetic-mechanical signals needed for seed cells to form bone.(2)Magnetic-responsive hydrogel can be used as a carrier to accurately regulate the release time of growth factors.(3)Under the three-dimensional microenvironment culture platform based on magnetically responsive hydrogel,the magnetic force at the interface between the magnetic response hydrogel and cells can activate cell surface sensitive receptors,enhance cell activity,and promote the integration of new bone and host bone.(4)The injectable magnetically responsive hydrogel can be used in the field of magnetic hyperthermia and biological imaging of bone tumors.(5)At present,magnetically responsive hydrogels are expected to mimic the anisotropic layered structure observed in natural bone tissue.However,most of the studies on magnetically responsive hydrogels focus on in vitro studies,and the mechanism of interaction between magnetically responsive hydrogels and the local microenvironment in vivo is still insufficient.(6)Therefore,based on the successful application of magnetic nanoparticles in magnetic resonance imaging,it is expected to optimize the properties of magnetic nanoparticles in the future to construct magnetic responsive hydrogels with suitable degradation properties,mechanical properties,and vascular functionalization,which can monitor changes in vivo in real time.

【Objective】 To explore the efficacy of retropubic midurethral synthetic sling (RMUS) in relieving urgency and urge urinary incontinence (UUI) symptoms in patients with mixed urinary incontinence (MUI). 【Methods】 Clinical data of 44 female MUI patients treated with RMUS during Jan.2018 and Dec.2020 in Shanghai Renji Hospital were retrospectively analyzed.All patients had positive results in stress test and Marshall-Marchetti test before operation, and 27 of them completed ICIQ-FLUTS-LF questionnaire.Urodynamic (UDS) tests suggested that 9 patients (20.5%) presented detrusor overactivity (DO).During RMUS procedure, the tension of the sling was adjusted based on the anatomical landmarks.The postoperative efficacy and improvement of urinary incontinence were analyzed. 【Results】 The patients aged (58.59±9.08) years, with a body mass index of 24.71±2.77.Among the 40 patients who completed telephone interview 2 years after surgery, the subjective cure rate was 85.0% (34/40).Among the 27 patients with records of questionnaires before and after surgery, there were significant differences in the incidence of urine leakage \[100% (27/27) vs. 18.5% (5/27)\], stress urinary incontinence (SUI) \[100% (27/27) vs. 18.5% (5/27)\] and UUI \[70.4% (19/27) vs. 29.6% (8/27)\] (P<0.05).However, no statistical differences were found regarding nocturia voiding episode (≥1 times), urgency, dysuria, hesitancy, strain to void, intermittent stream and enuresis (P>0.05).Based on preoperative UDS test, there were significant differences regarding the subjective cure rate in patients with or without preoperative DO \[55.6% (5/9) vs. 93.5% (29/31)\], incidence of SUI \[66.7%(4/6) vs. 4.8% (1/21)\], and UUI \[66.7% (4/6) vs. 19.0% (4/21)\] (P<0.05), while there was no statistical difference regarding urgency \[66.7% (4/6) vs. 33.3% (7/21)\] (P>0.05). 【Conclusion】 RMUS is effective in treating MUI patients with positive stress test and Marshall-Marchetti test results, which can relieve SUI and UUI symptoms, but has no effects on urgency symptoms.DO on preoperative urodynamics results in poorer subjective outcomes.