Objective: To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students. Methods: From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models. Results: The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49，95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99，95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49，95% CI =14.22~35.59, P <0.01). Conclusion Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.

This study explored the comorbidity mechanisms of coronary heart disease and depression from the perspectives of "constraint causing disease" and "disease causing constraint"， for which "constraint" is the link， and the key lies in the stagnation of qi. The heart storing manifestations in traditional Chinese medicine （TCM） encompasses most physiological processes of the circulatory system， the mental nervous system， and some functions of the endocrine system， and cardiovascular diseases and psychological disorders are closely related to it. In TCM， it is proposed that the stagnation of heart yang leading to "yang deficiency" is the pathogenesis of chest tightness， and emotional disturbance leading to the stagnation of yang qi aggravates the chest tightness， reflecting the process of "disease causing constraint". As the disease progresses， the appearance of phlegm and stasis further worsens the condition， reflecting the process of "constraint causing disease". Based on modern medical understanding， the abnormal accumulation of lipids， platelets， oxidative products， cytokines， and other substances constitute a form of "constraint"， which is also the material basis for the comorbidity of coronary heart disease and depression. These substances promote neuronal damage or apoptosis in the emotional and cognitive regions， inducing the onset of depression， reflecting the process of "disease causing constraint". Meanwhile， adverse emotions lead to sympathetic nerve excitement， resulting in the production of catecholamines， promoting platelet aggregation， elevating levels of inflammatory markers， and increasing the risk of coronary heart disease， reflecting the process of "disease causing constraint".

Objective:To evaluate the predictive value of serum 25-hydroxyvitamin D (25(OH)D) level for the clinical response and imaging response to anal fistula in patients with perianal fistulizing Crohn′s disease (PFCD) treated with ustekinumab (UST).Methods:From October 1, 2021 to June 30, 2023, 80 patients with active PFCD who received UST treatment at the Second Affiliated Hospital of Wenzhou Medical University were retrospectively collected. Harvey-Bradshaw index (HBI) was applied to evaluate the clinical activity of PFCD patients. Perianal disease activity index (PDAI) were used to evaluate the clinical outcomes of anal fistula and pelvic magnetic resonance imaging (MRI) were used to evaluate the imaging outcomes of anal fistula. Serum 25(OH)D levels were examined at week 0, 8, 16, and 24 after UST treatment. Binary logistic regression models were performed to analyze the relationship between the baseline serum 25(OH)D level and the clinical pathological characteristics. And the correlation between the serum 25(OH)D level and the clinical response to anal fistula at week 8 after UST treatment was analyzed. The relationship between clinical response and imaging response to anal fistula at week 24 was also analyzed. R software was employed to draw nomograms and calculate the C-index. Independent sample t test and chi-square test were used for statistical comparison. Results:Multifactorial binary logistic regression analysis showed that the baseline level of serum 25(OH)D was independently correlated with the baseline HBI and baseline PDAI in PFCD patients ( OR=1.45, 95% confidence interval (95% CI) 1.08 to 1.95, P=0.014; OR=1.39, 95% CI 1.01 to 1.92, P=0.042). At week 8 after UST treatment, the serum 25(OH)D level of patients with clinical response to fistula was higher than that of patients without clinical response ((21.77±6.17) μg/L vs. (16.72±6.39) μg/L), while the baseline PDAI was lower than that of patients without response (6.88±2.15 vs. 8.06±2.14), and the proportions of patients with previous failure of biologic therapy and with complex anal fistula were also lower than those of patients without response (42.4%, 14/33 vs. 66.0%, 31/47; 57.6%, 19/33 vs. 78.7%, 37/47), and the differences were statistically significant ( t=3.53 and 2.43, χ2=4.36 and 4.13; P=0.002, 0.022, 0.039 and 0.045). At week 24 after UST treatment, the serum level of 25(OH)D in patients with imaging response was higher than that in patients without response ((22.48±5.81) μg/L vs. (16.66±6.34) μg/L), and the proportion of patients with previous failure of biologic therapy and the proportion of patients with complex anal fistula was lower than that in patients without response (40.0%, 20/50 vs. 12/15; 60.0%, 30/50 vs. 14/15), and all the differences were statistically significant ( t=3.33, χ2=7.39 and 5.86; P=0.004, 0.011 and 0.038). Multifactorial binary logistic regression model analysis showed that the average serum 25(OH)D level and previous failure of biological therapy were 2 independent factors of clinical response to anal fistula at week 8 after UST treatment ( OR=1.11, 95% CI 1.02 to 1.21, P=0.012; OR=0.34, 95% CI 0.12 to 0.97, P=0.043), which were also 2 independent factors of clinical response to anal fistula ( OR=1.14, 95% CI 1.05 to 1.24, P=0.002; OR=0.30, 95% CI 0.11 to 0.89, P=0.029) and imaging response to anal fistula ( OR=1.20, 95% CI 1.05 to 1.36, P=0.006; OR=0.11, 95% CI 0.02 to 0.58, P=0.009) at week 24 after UST treatment. The nomograms showed the C-indexes of the clinical response to anal fistula at week 8 and week 24 after UST treatment were 0.78 (95% CI 0.68 to 0.89) and 0.76 (95% CI 0.64 to 0.87), respectively. The C-index of imaging response at week 24 after UST treatment was 0.85 (95% CI 0.76 to 0.95). Conclusions:In PFCD patients treated with UST, serum 25(OH)D levels and previous failure of biological therapy may independently affect the clinical response to anal fistula at week 8 and 24 after UST treatment, as well as the imaging response to anal fistula at week 24 after UST treatment.

Objective To explore the differences in the effectiveness of using different blood indicators individually,in combination,and for dynamic monitoring in the diagnosis,differential diagnosis,and prognosis of bacterial infections.Methods 1843 cases with infectious symptoms or signs from January 2015 to September 2022 at the People's Hospital of Yuxi City were selected as the case group,and 2298 uninfected individuals during the same period were selected as the control group.Blood indicators of the two groups were collected.Variables were grouped according to gender,age group,specimen type,etc.SPSS 24.0 and Medcalc 20.0 were used for statistical analysis.Results The individual diagnostic efficacy of various blood indicators for detecting infection ranges from 0.656 to 0.937.When used together,the efficacy ranges from 0.907 to 0.987.The efficacy of distinguishing between G+c and G-b in different specimens is as follows:when PCT is used alone in blood,the AUC is 0.875 for males and 0.769 for females.However,the individual diagnostic efficacy in male mucous secretions,sterile body fluids,and non-adult male sputum is all≤0.7.Yet,when used together,the efficacy is AUC(0.789,0.737,0.86)respectively.The dynamic monitoring of PCT,IL-6,CRP,WBC,and LAC in adult patients at 24 h,48 h,and 72 h after admission shows statistically significant differences in prognostic efficacy for G+c and G-b(P<0.05).Conclusions Blood indicators have a certain diagnostic value for determining whether there is a bacterial infection,and there are gender differences.The combined use of these indicators is more effective.The diagnostic value of using blood indicators alone or in combination for distinguishing between G+c and G-b in different types of specimens varies.The use of PCT alone in blood specimens is the most effective.For adult males,the combined use of body surface mucous secretions and sterile body fluids is most effective,while for underage males,the combined use of sputum is most effective.The combined use for females is not effective.Dynamic monitoring of PCT,CRP,IL-6,LAC,and WBC has a high value for evaluating the prognosis and therapeutic effect of infections.The evaluation of G+c infection is most effective at 24 hours for IL-6,and for G-b infection,it is most effective at 72 hours for PCT.

OBJECTIVE: To analyze the predictors of successful weaning off extracorporeal membrane oxygenation (ECMO) after extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: The clinical data of 56 patients with cardiac arrest who underwent ECPR in Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from July 2018 to September 2022 were retrospectively analyzed. According to whether ECMO was successfully weaning off, patients were divided into the successful weaning off group and the failed weaning off group. The basic data, duration of conventional cardiopulmonary resuscitation (CCPR, the time from cardiopulmonary resuscitation to ECMO), duration of ECMO, pulse pressure loss, complications, and the use of distal perfusion tube and intra-aortic balloon pump (IABP) were compared between the two groups. Univariate and multivariate Logistic regression analyses were performed to identify the risk factors for weaning failure of ECMO. RESULTS: Twenty-three patients (41.07%) were successfully weaned from ECMO. Compared with the successful weaning off group, patients in the failed weaning off group were older (years old: 46.7±15.6 vs. 37.8±16.8, P < 0.05), higher incidence of pulse pressure loss and ECMO complications [81.8% (27/33) vs. 21.7% (5/23), 84.8% (28/33) vs. 39.1% (9/23), both P < 0.01], and longer CCPR time (minutes: 72.3±19.5 vs. 54.4±24.6, P < 0.01), shorter duration of ECMO support (hours: 87.3±81.1 vs. 147.7±50.8, P < 0.01), and worse improvement in arterial blood pH and lactic acid (Lac) levels after ECPR support [pH: 7.1±0.1 vs. 7.3±0.1, Lac (mmol/L): 12.6±2.4 vs. 8.9±2.1, both P < 0.01]. There were no significant differences in the utilization rate of distal perfusion tube and IABP between the two groups. Univariate Logistic regression analysis showed that the factors affecting the weaning off ECMO of ECPR patients were pulse pressure loss, ECMO complications, arterial blood pH and Lac after installation [pulse pressure loss: odds ratio (OR) = 3.37, 95% confidence interval (95%CI) was 1.39-8.17, P = 0.007; ECMO complications: OR = 2.88, 95%CI was 1.11-7.45, P = 0.030; pH after installation: OR = 0.01, 95%CI was 0.00-0.16, P = 0.002; Lac after installation: OR = 1.21, 95%CI was 1.06-1.37, P = 0.003]. After adjusting for the effects of age, gender, ECMO complications, arterial blood pH and Lac after installation, and CCPR time, showed that pulse pressure loss was an independent predictor of weaning failure in ECPR patients (OR = 1.27, 95%CI was 1.01-1.61, P = 0.049). CONCLUSIONS Early loss of pulse pressure after ECPR is an independent predictor of failed weaning off ECMO in ECPR patients. Strengthening hemodynamic monitoring and management after ECPR is very important for the successful weaning off ECMO in ECPR.
Humans ; Extracorporeal Membrane Oxygenation ; Blood Pressure ; Retrospective Studies ; Perfusion ; Cardiopulmonary Resuscitation

Objective:To construct the content framework of the rehabilitation management application (APP) for patients with urinary incontinence after radical prostatectomy, so as to provide an effective network management platform for the rehabilitation management of patients wither urinary incontinence after radical prostatectomy.Methods:From November 2020 to May 2021, the content framework of rehabilitation management APP for patients with urinary incontinence after radical prostatectomy was initially constructed through literature review and group discussion. The objective sampling was used to select 15 experts from Beijing, Shanghai and other regions for two rounds of expert consultation, to construct the content framework of rehabilitation management APP for patients with urinary incontinence after radical prostatectomy.Results:Among two rounds of expert consultation, the effective recovery rates of the questionnaires were all 100.00% (15/15) , and the expert authority coefficients were 0.937 and 0.934, respectively. The Kendall harmony coefficients of all indicators in the second round of expert consultation ranged from 0.208 to 0.333, and the differences were all statistical (all P<0.01) . It was finally determined that the content framework of rehabilitation management APP for patients with urinary incontinence after radical prostatectomy included 3 first-level indicators, 10 second-level indicators, 43 third-level indicators, and 62 fourth-level indicators. Conclusions:The content framework of constructed rehabilitation management APP for patients with urinary incontinence after radical prostatectomy is highly scientific and practical, and can provide corresponding evidence.

Objective:To analyze the influence of factors before initiation of extracorporeal cardiopulmonary resuscitation (ECPR) on the prognosis of patients, so as to explore the intervention timing and improvement strategy of ECPR.Methods:A retrospective analysis was performed on 29 patients who underwent ECPR in the First Affiliated Hospital of Hunan Normal University (Hunan people's Hospital)from July 2018 to April 2021. Patients were divided into the survival group ( n = 13) and death group ( n = 16) according to whether they survived at discharge. The duration of conventional cardiopulmonary resuscitation (CCPR), initial heart rate before ECPR, the ratio of out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA), and the ratio of transported cases outside the hospital were compared between the two groups. According to different CCPR time, the patients were divided into the ≤45 min group, 45-60 min group and >60 min group to compare the hospital survival and sustained return of spontaneous circulation (ROSC) rate . According to the location of cardiac arrest, the patients from emergency department and other department were divided to compare the survival of IHCA. Results:The total survival rate was 44.83%, the average duration of extracorporeal membrane oxygenation (ECMO) was 114 (33.5, 142.5) h, and the average duration of CCPR time was 60 (44.5, 80) min. The duration of ECMO was longer in the survival group than in the death group ( P = 0.001). The duration of CCPR (the time from CPR to ECMO) in the survival group was significantly shorter than that in the death group ( P = 0.010). Patients with defibrillatory rhythm had higher hospital survival rate ( P = 0.010). OHCA patients had higher mortality than IHCA patients ( P = 0.020). Mortality of patients transferred from other hospitals was higher ( P = 0.025). Hospital survival and ROSC decreased in turn by CCPR duration ≤ 45 min, 45-60 min, and > 60 min ( P = 0.001). The location of CA occurrence had no impact on the hospital survival rate of IHCA patients ( P=0.54). Conclusions:Hospital survival of ECPR is higher than that of CCPR. ECPR is effective for refractory cardiac arrest. The prognosis of ECPR is significantly related to the duration of CCPR, initial heart rate, and location of CA. Education and team training should be strengthened to improve the survival rate of ECPR.

Objective:To establish a nomogram prediction model for the risk of postoperative delirium in elderly patients with chronic subdural hematoma.Methods:A total of 450 elderly patients with chronic subdural hematoma who were admitted into Shengjing Hospital of China Medical University from January 2017 to January 2020 were selected as the research objects. The patients were divided into the delirium group ( n=135) and the non-delirium group ( n=315) according to whether they had delirium. The indexes of patients in two groups were compared and analyzed. Univariate analysis and multivariate Logistic regression analysis were used to investigate the independent risk factors for postoperative delirium in elderly patients with chronic subdural hematoma, and a prediction model for the risk of delirium was establish based on independent risk factors. ROC curve and calibration curve were used to evaluate the discriminant ability and predictive effectiveness of the model. Results:In 450 elderly patients with chronic subdural hematoma after surgery, 135 cases of delirium occurred postoperatively, and the incidence of delirium was 30.0%. Univariate analysis showed that there were statistically significant differences in delirium incidence among patients with different ages, alcoholism history, Markwalder grade and postoperative pain grade (χ 2=23.069, 27.325, 36.081, 44.834; P<0.05) . Logistic regression analysis showed that advanced age, preoperative Markwalder grade Ⅳ, history of alcoholism and severe postoperative pain were independent risk factors for postoperative delirium ( P<0.05) . A nomogram prediction model for postoperative delirium risk in elderly patients with chronic subdural hematoma was established based on independent risk factors. The Bootstrap internal verification method proved that the prediction accuracy of the model was good ( C- index was 0.904) , and the area under the ROC curve calculated by the Nomogram model was 0.904. Conclusions:The delirium risk nomogram prediction model constructed in this study has good accuracy, discrimination and good predictive ability. It can improve the screening efficiency for elderly patients with chronic subdural hematoma who are at high risk of developing delirium after surgery.