Background: and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD). Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert’s syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al. Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41–2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43–2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45–2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson–Neyman analyses showed cut-off concentrations of 22.3–22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not. Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.

Objective:To assess health-related quality of life and disease burden of Chinese Phenylketonuria(PKU)patients and inform optimized management and support strategies.Methods:A cross-sectional survey is conducted to explore questionnaires.The Delphi method was applied to form a standardized questionnaire.Results:A total of 263 valid questionnaires were collected.The average patient age was 7.6 years.Younger patients reported better quality of life.Mean total medical cost per patient was 238 461.9 yuan,exceeding the 2024 national per capita disposable income.Conclusion:PKU patients are facing significant challenges in both quality of life and economic burden.

Objective:To analyze the changes of peripheral blood CD 4+ T lymphocyte subsets caused by nanosecond pulse ablation in C57BL/6J liver cancer mice and its effect on the immunity of liver cancer mice. Methods:According to the randomallocation, 32 female C57BL/6J mice weighing 18-20 g and aged 8-10 weeks were divided into the blank control group (Group A), the liver cancer control group (Group B), the radical liver lobectomy group (Group C), and the nanosecond pulse ablation treatment group (Group D), with 8 mice in each group. The in situ liver cancer models for mice in groups B, C, and D were established using Hepa 1-6 hepatoma cell line. On the 7th day after modeling, group C underwent liver lobectomy, and group D underwent nanosecond pulse ablation. After 7 days of treatment, the subtypes Th1, Th2, Th17 and Treg cell levels of CD 4+ T cells in the peripheral blood of the four groups of mice were detected by flow cytometry. Results:Flow cytometry was used to detect and analyze the proportions of CD 4+ T cell subsets Th1, Th2, Th17 and Treg in the peripheral blood of four groups of mice. Comparisons of each index among the groups showed statistically significant differences (all P<0.001). The proportion of Th1 cells detected by flow cytometry was (8.4±1.1) % in group A, (8.5±1.5)% in group D, (3.5±0.5)% in group B, and (2.4±0.5)% in group C. Both group A and Group D were higher than group B and group C, and the differences were statistically significant (all P<0.001). The proportion of Th2 cells detected by flow cytometry was (5.1±0.8)% in group A, (5.1±1.3)% in Group B, (5.4±0.9)% in group C, and (3.6±0.9)% in group D. The proportion of Th2 cells in groups A, B, and C was higher than that in group D, and the differences were statistically significant (all P<0.05). The proportion of Th17 cells detected by flow cytometry was (1.5±0.6)% in group A, (8.6±1.3)% in group B, (8.2±1.5)% in group C, and (1.7±0.3)% in group D. The proportion of Th17 cells in both group B and group C was higher than that in group A and group D, and the differences were statistically significant (all P<0.001). The proportion of Treg cells detected by flow cytometry was (7.0±0.9)% in group B, (6.8±0.9)% in group C, (3.8±0.8)% in group D, and (0.9±0.2)% in group A. The proportion of Treg in group B and group C was higher than that in group A and group D, and the difference was statistically significant (all P<0.001). Conclusion:Nanosecond pulse ablation for liver cancer in mice can regulate CD 4+ T cell subsets in peripheral blood, enhance the immune response of Th1 cells, inhibit the expression of Th2, Th17 and Treg cells, and improve the immunosuppressive state caused by liver cancer.

Objective To explore the effect of collateral status on prognosis in elderly patients with acute ischemic stroke due to large vessel occlusion(AIS-LVO)after Solitaire stent retriever in combination with the intracranial support catheter aspiration for mechanical thrombectomy(SWIM),and construct a prediction model for prognosis.Methods A retrospective analysis was performed on 240 elderly AIS-LVO patients who underwent SWIM technique in our hospital be-tween February 2019 and February 2024.According to gender,age,occlusion sites and TOAST classifications,they were divided into a modeling group(180 cases)and a verification group(60 cases)in a ratio of 3∶1.Based on the results of modified Rankin scale(mRS)at 3 months after surgery,the patients in the modeling group were further divided into good prognosis subgroup(mRS score:0-2,97 cases)and poor prognosis subgroup(mRS score:3-6,83 cases).Multivari-ate logistic regression analysis was applied to evaluate the relationship between preoperative col-lateral circulation status and prognosis and to identify the influencing factors for prognosis.Then a prediction model for prognosis was constructed,and its performance was evaluated by ROC curve analysis.Results In the modeling group at 3 months of follow-up,the poor prognosis subgroup had significantly larger proportions of posterior circulation occlusion,cardiogenic embolism,ASITN/SIR grades 3-4 and hemorrhage transformation,higher NIHSS score at admission and longer interval from onset to vascular recanalization,while lower ASPECTS score at admission when compared with the good prognosis subgroup(P＜0.01).Multivariate logistic regression analysis showed that occlusion site,TOAST classification,NIHSS score at admission,interval from onset to vascular recanalization and hemorrhage transformation were independent risk fac-tors for poor prognosis,while ASPECTS score at admission and collateral circulation were protec-tive factors of good prognosis in the elderly AIS-LVO patients after SWIM technique(P＜0.01).Hosmer-Lemeshow test showed that the regression equation obtained goodness of fit in the mod-eling group(P=0.435).ROC curve analysis revealed that the AUC,sensitivity and specificity of then constructed prediction model for poor prognosis was 0.855[95％CI(0.797-0.913)],81.93％and 79.38％,respectively.The model was further verified in the data of the verification group(34 cases in good prognosis and 26 cases with poor prognosis),the AUC value,sensitivity and speci-ficity was 0.839[95％CI(0.732-0.947)],84.62％and 79.41％,respectively.Conclusion Our pre-diction model constructed based on screened risk factors for poor prognosis has good validity in patients with AIS-LVO after SWIM technique,which can identify the patients at high risk for poor prognosis.

Objective:To assess health-related quality of life and disease burden of Chinese Phenylketonuria(PKU)patients and inform optimized management and support strategies.Methods:A cross-sectional survey is conducted to explore questionnaires.The Delphi method was applied to form a standardized questionnaire.Results:A total of 263 valid questionnaires were collected.The average patient age was 7.6 years.Younger patients reported better quality of life.Mean total medical cost per patient was 238 461.9 yuan,exceeding the 2024 national per capita disposable income.Conclusion:PKU patients are facing significant challenges in both quality of life and economic burden.

Objective To explore the effect of collateral status on prognosis in elderly patients with acute ischemic stroke due to large vessel occlusion(AIS-LVO)after Solitaire stent retriever in combination with the intracranial support catheter aspiration for mechanical thrombectomy(SWIM),and construct a prediction model for prognosis.Methods A retrospective analysis was performed on 240 elderly AIS-LVO patients who underwent SWIM technique in our hospital be-tween February 2019 and February 2024.According to gender,age,occlusion sites and TOAST classifications,they were divided into a modeling group(180 cases)and a verification group(60 cases)in a ratio of 3∶1.Based on the results of modified Rankin scale(mRS)at 3 months after surgery,the patients in the modeling group were further divided into good prognosis subgroup(mRS score:0-2,97 cases)and poor prognosis subgroup(mRS score:3-6,83 cases).Multivari-ate logistic regression analysis was applied to evaluate the relationship between preoperative col-lateral circulation status and prognosis and to identify the influencing factors for prognosis.Then a prediction model for prognosis was constructed,and its performance was evaluated by ROC curve analysis.Results In the modeling group at 3 months of follow-up,the poor prognosis subgroup had significantly larger proportions of posterior circulation occlusion,cardiogenic embolism,ASITN/SIR grades 3-4 and hemorrhage transformation,higher NIHSS score at admission and longer interval from onset to vascular recanalization,while lower ASPECTS score at admission when compared with the good prognosis subgroup(P＜0.01).Multivariate logistic regression analysis showed that occlusion site,TOAST classification,NIHSS score at admission,interval from onset to vascular recanalization and hemorrhage transformation were independent risk fac-tors for poor prognosis,while ASPECTS score at admission and collateral circulation were protec-tive factors of good prognosis in the elderly AIS-LVO patients after SWIM technique(P＜0.01).Hosmer-Lemeshow test showed that the regression equation obtained goodness of fit in the mod-eling group(P=0.435).ROC curve analysis revealed that the AUC,sensitivity and specificity of then constructed prediction model for poor prognosis was 0.855[95％CI(0.797-0.913)],81.93％and 79.38％,respectively.The model was further verified in the data of the verification group(34 cases in good prognosis and 26 cases with poor prognosis),the AUC value,sensitivity and speci-ficity was 0.839[95％CI(0.732-0.947)],84.62％and 79.41％,respectively.Conclusion Our pre-diction model constructed based on screened risk factors for poor prognosis has good validity in patients with AIS-LVO after SWIM technique,which can identify the patients at high risk for poor prognosis.

Objective:To analyze the changes of peripheral blood CD 4+ T lymphocyte subsets caused by nanosecond pulse ablation in C57BL/6J liver cancer mice and its effect on the immunity of liver cancer mice. Methods:According to the randomallocation, 32 female C57BL/6J mice weighing 18-20 g and aged 8-10 weeks were divided into the blank control group (Group A), the liver cancer control group (Group B), the radical liver lobectomy group (Group C), and the nanosecond pulse ablation treatment group (Group D), with 8 mice in each group. The in situ liver cancer models for mice in groups B, C, and D were established using Hepa 1-6 hepatoma cell line. On the 7th day after modeling, group C underwent liver lobectomy, and group D underwent nanosecond pulse ablation. After 7 days of treatment, the subtypes Th1, Th2, Th17 and Treg cell levels of CD 4+ T cells in the peripheral blood of the four groups of mice were detected by flow cytometry. Results:Flow cytometry was used to detect and analyze the proportions of CD 4+ T cell subsets Th1, Th2, Th17 and Treg in the peripheral blood of four groups of mice. Comparisons of each index among the groups showed statistically significant differences (all P<0.001). The proportion of Th1 cells detected by flow cytometry was (8.4±1.1) % in group A, (8.5±1.5)% in group D, (3.5±0.5)% in group B, and (2.4±0.5)% in group C. Both group A and Group D were higher than group B and group C, and the differences were statistically significant (all P<0.001). The proportion of Th2 cells detected by flow cytometry was (5.1±0.8)% in group A, (5.1±1.3)% in Group B, (5.4±0.9)% in group C, and (3.6±0.9)% in group D. The proportion of Th2 cells in groups A, B, and C was higher than that in group D, and the differences were statistically significant (all P<0.05). The proportion of Th17 cells detected by flow cytometry was (1.5±0.6)% in group A, (8.6±1.3)% in group B, (8.2±1.5)% in group C, and (1.7±0.3)% in group D. The proportion of Th17 cells in both group B and group C was higher than that in group A and group D, and the differences were statistically significant (all P<0.001). The proportion of Treg cells detected by flow cytometry was (7.0±0.9)% in group B, (6.8±0.9)% in group C, (3.8±0.8)% in group D, and (0.9±0.2)% in group A. The proportion of Treg in group B and group C was higher than that in group A and group D, and the difference was statistically significant (all P<0.001). Conclusion:Nanosecond pulse ablation for liver cancer in mice can regulate CD 4+ T cell subsets in peripheral blood, enhance the immune response of Th1 cells, inhibit the expression of Th2, Th17 and Treg cells, and improve the immunosuppressive state caused by liver cancer.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective By using high-resolution magnetic resonance angiography to display the vascular wall imaging so as to evaluate the relationship between plaque characteristics and postoperative in-stent restenosis(ISR)in patients with middle cerebral artery stenosis.Methods A total of 66 patients with symptomatic atherosclerotic middle cerebral artery stenosis,who were admitted to the Affiliated Hospital of Chengde Medical College of China from January 2019 to March 2023,were enrolled in this study.Before stent implantation,all the 66 patients completed high-resolution magnetic resonance angiography.According to the postoperative imaging follow-up results,the patients were divided into ISR group and non-ISR group.The preoperative plaque characteristics,which were assessed by high-resolution magnetic resonance imaging,were compared between the two groups.Results ISR group had 14 patients and non-ISR group had 52 patients.Most of the plaques were located in the inferior lateral wall(37.8％)and the ventral lateral wall(28.7％),in which no statistically significant difference existed between the two groups(P＞0.05).Compared with non-ISR group,in ISR group the negative remodeling degree was obviously higher and the difference between the two groups was statistically significant(x2=6.026,P=0.049).The plaque load in ISR group and non-ISR group was 79.09±8.82 and 69.46±10.49 respectively,and the difference between the two groups was statistically significant(t=3.143,P=0.003).The homocysteine level in ISR group and non-ISR group was(16.02±4.24)mol/L and(12.05±3.34)mol/L respectively,and the difference between the two groups was statistically significant(t=3.717,P＜0.001).In ISR group,there were more significantly contrast-enhanced plaques(78.5％vs.42.3％),with statistically significant difference(x2=6.311,P=0.043).Multivariate logistic regression analysis showed that plaque load(OR=1.225,95％CI:1.040-1.443,P=0.015)and homocysteine level(OR=1.676,95％CI:1.150-2.442,P=0.007)were the independent risk factors for ISR.ROC curve analysis showed that in predicting ISR,the AUC,specificity and sensitivity of the plaque load were 0.765(95％CI:0.622-0.908,P=0.002),0.731 and 0.714 respectively,which of the homocysteine level were 0.767(95％CI:0.623-0.911,P=0.002),0.942 and 0.500 respectively.The combination use of plaque load and homocysteine level could achieve the best predictive effect,its AUC,specificity and sensitivity were 0.887(95％CI:0.794-0.981,P＜0.001),0.904 and 0.714 respectively.Conclusion The plaque load assessed by high-resolution magnetic resonance imaging and the homocysteine level have higher specificity and sensitivity in predicting ISR in patients with middle cerebral artery stenosis.

Abstract Compared with normal children, leftbehind children who experience parent child separation receive less care and attention from their parents, and are more likely to have cognitive and behavioral adaptation problems, thus leading to an elevated risk of depression. The study systematically examines the effects of parent child separation type, separation duration and separation age on depression among left-behind children. Attachment theory, interpersonal relationship, theory attribution theory and behavior theory have been used to explain how parentchild separation influences depression among left-behind children, so as to provide reference for relevant research and mental health education for left-behind children.