ObjectiveTo observe the effects of Xiaoyaosan on glucagon-like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1r） and protein kinase A （PKA）/cAMP response element binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathways in the hippocampal CA1 region of rats under chronic restraint stress （CRS），and to explore the mechanism of this formula to alleviate anxiety and depression-like behaviors. Methods40 specific pathogen-free male Sprague-Dawley （SD） rats were randomly divided into normal，model，Xiaoyaosan，and fluoxetine groups，with 10 rats in each group. CRS was used to induce anxiety and depression-like behaviors. The rats in the Xiaoyaosan group were gavaged with aqueous solution of traditional Chinese medicine formula granules （7.36 g·kg^-1·d^-1），while those in the fluoxetine group were gavaged with aqueous solution of fluoxetine （2 mg·kg^-1·d^-1）. Body weight was measured on days 0，7，14，and 21 of the experiment. On days 0 and 22 of the experiment，the sucrose preference test （SPT），forced swimming test （FST），and open field test （OFT） were performed. The pathological morphology of the hippocampal CA1 region was observed by Nissl staining. The relative mRNA expression of post-synaptic density protein-95 （PSD95） and synapsin （SYP） was detected by reverse transcription quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect expression of proteins in the GLP-1/GLP-1r and PKA/CREB/BDNF pathways in the hippocampal CA1 region. ResultsAfter CRS modeling，compared with the normal group，the rats of the model group had anxiety and depression-like behavioral manifestations，neuronal damage in the hippocampal CA1 region，significantly downregulated expression of synaptic plasticity markers PSD95 and SYP genes （P<0.01），and inhibition of GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways （P<0.05，P<0.01）. Compared with the model group，the Xiaoyaosan group exhibited alleviated anxiety and depression-like behaviors，reduced neuronal damage in the hippocampal CA1 region， significantly increased expression of PSD95 and SYP genes （P<0.01），and the activation of the GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways （P<0.05，P<0.01）. ConclusionXiaoyaosan can alleviate anxiety and depression-like behaviors in CRS rats by improving synaptic plasticity in the hippocampal CA1 region. The mechanisms may be related to the activation of the GLP-1/GLP-1r pathway and its mediated PKA/CREB/BDNF signaling pathway by the formula.

Objective: To understand the impact of childhood trauma on psychological distress among upper grade elemetary school students, and to explore the mediating role of leisure activities in the relationship, so as to provide a basis for developing mental health intervention strategies. Methods: From August to November 2024, a combination of convenience sampling and stratified cluster random sampling was employed to recruit 1 373 fourth to sixth grade students from four primary schools in Harbin. The Childhood Trauma Questionnaire(CTQ), a self designed leisure activity scale (including active and passive leisure activities), and the Kessler Psychological Distress Scale (K10) were used to assess childhood trauma experiences, leisure activities, and levels of psychological distress. Spearman correlation analysis and linear regression analysis were conducted to explore the relationships among childhood trauma, leisure types, leisure time, and psychological distress. Based on the mediation analysis framework proposed by Hayes (Model 4), the mediating role of leisure types in the relationship between childhood trauma and psychological distress was examined. Results: Totally 19.1% of the upper elemetary school students exhibited psychological distress, while 30.2% had experienced childhood trauma. During school days, 64.6% of the students were reported of having leisure time concentrated between 1 and 5 hours per day, whereas 67.4% reported leisure time exceeding 5 hours per day on weekends. After controlling for potential demographic confounders such as gender, grade, ethnicity, household registration, being an only child, parents educational level, co residence, and whether parents are first time married,linear regression analysis showed that childhood trauma experience had positive predictive effect on psychological distress in upper primary school students( β =0.20, P <0.01). Leisure time showed no statistically significant association with psychological distress, both on school days ( β =-0.58 to -0.56) and weekends ( β =0.26- 0.98 )(all P >0.05). Active leisure activities were negatively associated with psychological distress ( β =-0.20), while passive leisure activities were positively associated with psychological distress ( β =0.29)(both P <0.01). Leisure type partially mediated the relationship between childhood trauma and psychological distress, accounting for 11.7% of the indirect effect. Conclusion Childhood trauma experiences positively predict psychological distress in upper elementary school students, and affect psychological distress through active leisure and passive leisure.

Objective: To evaluate the effects of dietary intervention on blood pressure and renal function in patients with hypertensive nephropathy, so as to provide dietary and nutritional guidances for this population. Methods: Hypertensive nephropathy patients who were treated at Zhucheng People's Hospital from March 2023 to February 2024 were selected as the study subjects and randomly divided into the intervention group and the control group. The control group received routine antihypertensive treatment and health lifestyle guidance. On the basis of the treatment and guidance received by the control group, the intervention group implemented dietary intervention in accordance with the Clinical Practice Guidelines for Nutritional Therapy of Chronic Kidney Disease in China (2021 edition) for a period of 3 months. Systolic blood pressure (SBP), diastolic blood pressure (DBP) were measured before and after the intervention, and serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), cystatin and β2-microglobulin were detected. Differences of indicators before and after intervention between the two groups were compared using generalized estimation equation. Results: A total of 83 patients with hypertensive nephropathy were followed up, including 43 cases in the intervention group and 40 cases in the control group. There were no statistically significant differences in gender, age, body mass index, duration of hypertension, family history of hypertension, hypertension grade, physical activity index, or smoking status between the two groups (all P>0.05). The differences in SBP, DBP, Scr, BUN, and UA between the two groups, as well as the differences before and after the intervention, were statistically significant, and there was an interaction between the groups and the intervention time (all P<0.05). After intervention, the levels of SBP, DBP, Scr, BUN, and UA in the intervention group were lower than those in the control group (all P<0.05). The differences in cystatin and β2-microglobulin between the two groups and before and after the intervention were not statistically significant, and there was no interaction between the groups and the intervention time (all P>0.05). Conclusion Dietary intervention has a certain effect on reducing blood pressure and improving renal function indicators in patients with hypertensive nephropathy.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

OBJECTIVE To investigate the effects of alirocumab combined with atorvastatin on clinical efficacy and safety of patients with acute coronary syndrome （ACS） who underwent percutaneous coronary intervention （PCI）. METHODS A total of 207 patients with ACS who underwent PCI in our hospital from January 2021 to December 2023 were randomly divided into alirocumab group， ezetimibe group and control group， with 69 cases in each group. All patients received routine thrombosis prevention and antihypertensive treatment after PCI. On this basis， patients in the control group were treated with atorvastatin （20 mg/time， once a day）； patients in the ezetimibe group were treated with ezetimibe （10 mg/time， once a day） + atorvastatin （20 mg/time， once a day）； patients in the alirocumab group were treated with alirocumab （75 mg/time， once every 2 weeks） + atorvastatin （20 mg/time， once a day）. All patients in the three groups were treated for 8 weeks and followed up for another 6 months after treatment. The levels of cardiac function and lipid metabolism indices before and after treatment， as well as the occurrence of major adverse cardiovascular event （MACE） and other adverse drug reaction （ADR） during the follow-up period were compared among the three groups. RESULTS After treatment for 8 weeks， the levels of cardiac function and lipid metabolism indices in the three groups were significantly improved compared with those before treatment （P＜0.05）. Compared with the control group and ezetimibe group， the left ventricular ejection fraction in the alirocumab group was significantly increased， and the left ventricular end-diastolic diameter （LVEDD） was significantly shortened （P＜0.05）. Compared with control group， LVEDD of ezetimibe group was significantly shortened （P＜0.05）， the levels of total cholesterol， triglyceride and low-density lipoprotein cholesterol in the alirocumab group and ezetimibe group were significantly decreased （P＜0.05）. During the follow-up period， there was no significant difference in the total incidence of MACE and the total incidence of other ADR such as headache and abdominal pain among the three groups （P＞0.05）. CONCLUSIONS Alirocumab combined with atorvastatin can significantly improve cardiac function and regulate lipid metabolism indices in patients with ACS after PCI without increasing the risk of MACE or other ADR.

Objective:To investigate and analyze the thyroid examination results and influencing factors of interventional radiation workers in Tianjin.Methods:In February 2023, A convenient sampling method was used to select the staff engaged in interventional radiation work in an occupational health inspection institution in Tianjin from 2020 to 2022 as the study object. After excluding the incomplete data, 1080 people were included, and 363 medical staff with non-radiological work during the same period were included as the control group. To analyze the individual doses and occupational health examination data of interventional radiation workers, and to analyze the possible influencing factors of thyroid abnormalities.Results:The cumulative dose M ( Q1, Q3) of interventional radiation workers was 1.039 (0.528, 1.905) mSv. The levels of FT 3 and FT 4 in the intervention group were higher than those in the control group, while TSH levels were lower than those in the control group ( Z=4.84、6.03、-5.82, P<0.05). The levels of FT 3 and FT 4 in female interventional radiation workers were lower than those in males, while the levels of TSH were higher than those in males ( Z= -17.54、-6.65、3.61, P<0.05). There were statistically significant differences in FT 3 levels among different ages, differen tradiation exposure years, different initial age of exposure to radiation, and different cumulative doses ( H=47.22、11.33、16.70, Z=-2.48, P<0.05). There were statistically significant differences in thyroid ultrasound abnormalities among different genders, different ages, different initial age of exposure to radiation, and different cumulative doses ( χ2=28.02、61.12、17.87、11.30, P<0.05). The results of logistic regression analysis showed that the influencing factors of FT 3 distributed in the low-level group were female ( OR=10.53, 95% CI: 7.66-14.47, P<0.05), and age 40-49, ≥50 years old ( OR=2.40, 95% CI: 1.12-5.14 OR=3.79, 95% CI: 1.59-9.03, P<0.05). The influencing factors of thyroid ultrasound abnormalities were female ( OR=1.92, 95% CI: 1.48-2.50, P<0.05) and age ≥50 years old ( OR=3.93, 95% CI: 1.91-8.09, P<0.05) . Conclusion:Long term low dose ionizing radiation has a certain effect on FT 3, FT 4 and TSH levels of interventional radiation workers. Gender and increased age are possible influencing factors of the decreased FT 3 levels and thyroid ultrasound abnormalities.

Objective:To explore the related risk factors of neonatal necrotizing enterocolitis (NEC) by constructing and comparing nine regression models.Methods:All NEC patients admitted to the neonatal internal medicine department, neonatal surgery department, and neonatal intensive care unit of Shanxi Provincial Children's Hospital (Shanxi Provincial Maternity and Child Health Center) from 2020 to 2022 were included as the case group. A control group consisted of children admitted during the same period based on the inclusion and exclusion criteria. The NEC data collected were used for feature selection by using the Boruta algorithm. Logistic regression, multi-decision tree gradient boosting, efficient gradient one-sided sampling, random forest, decision tree, gradient boosting decision tree (GBDT), neural network, support vector machine, and K-nearest neighbor models were constructed. The optimal model was selected through rigorous comparison and Shap explainable analysis was performed on the GBDT model.Results:Thirteen key factors were identified through screening for nine regression models construction. After strict comparison and analysis, the GBDT model showed higher stability compared with other eight regression models. In the validation set, the area under the receiver operating characteristic curve of the GBDT model was 0.958, with an accuracy of 0.925, and sensitivity and specificity of 0.827 and 0.950, respectively. Shap explainable analysis on the GBDT model revealed that suffering from anemia, non-invasive ventilator use, procalcitonin use, premature birth, and low birth weight increased the risk for NEC, while breastfeeding and probiotics decreased the risk for NEC.Conclusion:This study identified the risk factors and protective factors for NEC by using the GBDT model, which provided evidnce for the prevention and treatment of NEC.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.