BackgroundAdverse childhood experiences （ACEs） are strong predictors of psychopathology across the lifespan， exerting extensive adverse effects on physical and mental health during early development. While ACEs increase the risk of childhood psychopathology， sleep quality and impair cognitive function， the early neurobiological mechanisms mediating ACE-induced cognitive impairment remain unclear. ObjectiveTo explore the association between ACEs exposure and the risk of psychopathology， sleep disorders， and cognitive function， and to examine the mediating role of the putamen volume in the relationship between ACEs and cognitive function from a neurodevelopment perspective. MethodsData were obtained from the Adolescent Brain Cognitive Development （ABCD） study， comprising 10 572 children aged 9 to 10. Participants were categorized into five groups based on the cumulative score of ACEs reported by their parents and the children themselves： no-exposure group （0 types of ACEs）， the one-exposure group， the two-exposure group， the three-exposure group， and the high-risk exposure group （≥ 4 types of ACEs）. Logistic regression analysis was employed to evaluate the association between ACEs and psychopathological symptoms ［T score of the Child Behavior Checklist （CBCL） ≥ 65］. Multiple linear regression analysis was ultilized to analyze the correlations between ACEs and the scores of the Sleep Disturbance Scale for Children （SDSC）， the NIH Toolbox Cognition Battery （NIHTB-CB）， as well as the multiple structures in the cerebral cortex and subcortex. The Bootstrap method was applied to test the mediating effect of the putamen volume between ACEs and neurocognitive function. ResultsAfter adjusting for confounders， ACEs cumulative score was correlated with children's psychopathological symptoms in a dose-response manner. Compared with the no-exposed group， the high-risk exposure group had a 2.08-fold （OR=2.080， 95% CI： 1.401–3.088） increased risk of internalizing problems and a 3.13-fold （OR=3.132， 95% CI： 1.703–5.760） increased risk of externalizing problems， and the risk of conduct problems was 4.68 times that of the no-exposed group （OR=4.681， 95% CI： 2.528–8.669）. ACEs cumulative score positively predicted the total score of SDSC （β=0.080， 95% CI： 0.059–0.102）， with relatively stronger predictive effects on sleep-wake transition disorder （β=0.086， 95% CI： 0.063–0.109） and sleep onset and maintenance disorder （β=0.066， 95% CI： 0.043–0.089）. In terms of neurocognition and brain structure， ACEs cumulative score negatively predicted the overall cognitive composite score （β=-0.025， 95% CI： -0.050–-0.001）， the crystallized cognitive composite score （β=-0.035， 95% CI： -0.060–-0.010）， the volume of the left putamen nucleus （β=-0.025， 95% CI： -0.046– 0.003）， and the volume of the right putamen nucleus （β=-0.023， 95% CI： -0.044– 0.003）. The total putamen volume played a partial mediating role between ACEs and the overall cognitive composite score， the effect value was -0.002 （95% CI： -0.004–-0.001）， accounting for 7.49% of the total effect. ConclusionACEs exposure may increase the risk of psychopathological and sleep disturbances in children and may impair neurocognitive function. Reduced putamen volume may serve a potential neurobiological pathway underlying the impact of ACEs on childhood cognition. ［Funded by National Natural Science Foundation of China-Young Scientists Program （number， 82401763）； Sichuan University West China Hospital Full-time Postdoctoral Research and Development Fund Project （number， 2023HXBH084）］

Objective To evaluate the clinical efficacy of hip-knee-ankle active and passive exercise therapy in patients with early-to mid-stage knee osteoarthritis(KOA).Methods A total of 180 patients with early to mid-stage knee osteoarthritis(KOA)were recruited from the First Affiliated Hospital of Hebei University of Tradi-tional Chinese Medicine between March 2023 and March 2024.Patients were randomly assigned to one of four groups:active movement group,passive movement group,combined movement group,and control group,with 45 patients in each group.The active movement group received hip-knee-ankle active movement therapy daily until the end of follow-up.The passive movement group underwent hip-knee-ankle passive movement therapy three times per week for two weeks.The combined movement group received both active and passive therapies.The control group was administered oral celecoxib capsules(200 mg once daily for two weeks).Joint function was assessed in all four groups before treatment,at two weeks post-treatment,and at 14 weeks post-treatment.The primary outcome measure was the WOMAC joint function score,while secondary outcomes included the WOMAC pain score,stiffness score,and quality of life score(SF-12).Results A total of 160 patients completed the trial,with 39 in the active group,42 in the passive group,40 in the combined group,and 39 in the control group.There were no significant differences in baseline characteristics among the groups(P>0.05).Compared to baseline,the WOMAC scores for function,pain,and stiffness in the passive,combined,and control groups decreased significantly at both 2 and 14 weeks post-treatment(P<0.05),while the SF-12 scores increased significantly(P<0.05).Between 2 and 14 weeks post-treat-ment,the active and combined groups showed further significant decreases in WOMAC function,pain,and stiffness scores(P<0.05)and increases in SF-12 scores(P<0.05).At 2 weeks post-treatment,compared to the control group,the passive and combined groups exhibited significantly lower WOMAC function scores(P<0.05),with no significant difference between the passive and combined groups(P>0.05).By 14 weeks post-treatment,the active and combined groups demonstrated significantly lower WOMAC function scores(P<0.05),with the combined group showing a significantly lower score than the active group(P<0.05).Conclusion The four therapeutic approaches demonstrate a certain degree of efficacy in improving joint function for patients with early and mid-stage KOA.The passive therapy group exhibits superior short-term outcomes,while the active therapy group shows better long-term benefits.The combined therapy group presents notable advantages in both short-term and long-term effi-cacy,although its short-term effectiveness does not surpass that of the passive therapy group.It is recommended for patients with early and mid-stage KOA who have underlying gastrointestinal and cardiovascular conditions.

Objective To analyze temporal trends in infectious disease burden among Chinese elderly(≥60 years)using data from the Global Burden of Disease Study(GBD 2021),evaluate age-period-cohort effects on disease burden,predict trends through 2045,and propose evidence-based medication management strategies.Methods We conducted a threefold analysis of infectious disease burden from 1990 to 2021 using Joinpoint regression to identify temporal trends,Age-Period-Cohort(APC)modeling to disentangle epidemiological effects,and Nordpred projections for 2045 disease burden estimates.Results Over 32 years,all infectious disease categories except HIV/AIDS and sexually transmitted infections demonstrated significant declines.Enteric infections showed the most rapid reductions in mortality(AAPC=-7.85,P﹤0.001)and disability-adjusted life year rates(DALYR;AAPC=-7.18,P﹤0.001).We also found a significant decrease in the incidence of tropical diseases and malaria(AAPC=-6.77,P﹤0.001).APC analysis found that the age effect was mostly negative in terms of the annual percentage change in mortality and DALYR for each disease,except for HIV/AIDS,with an overall decline in period risk over time,and a generally higher risk of morbidity and mortality for the early birth cohort,and an overall decline in the risk of each disease as the year of birth progressed,but the risk of HIV/AIDS death and DALY period and cohort risks trended upward.While the overall risk for certain diseases was slightly higher in males compared to females,the trends were largely consistent across both sexes.In terms of projections,the absolute prevalence of respiratory infections and tuberculosis in terms of number of cases and age-standardized rates,and the growth of the disease burden of HIV/AIDS were particularly prominent,making them important health challenges for the future.The burden of disease in the elderly often results in issues such as potential polypharmacy,which must be addressed to improve medication management.Conclusions China has achieved remarkable progress in reducing infectious disease burdens among older adults,though HIV/AIDS and sexually transmitted infections present an escalating public health threat.These findings advocate for enhanced surveillance systems,age-specific prevention strategies,and precision medication protocols to optimize therapeutic outcomes in geriatric populations.

With the advancement of endovascular therapy(EVT)techniques,the recanalization rate for patients with ischemic stroke(IS)has exceeded 80%.However,more than 50%of patients fail to achieve favorable neurological outcomes following recanalization,a phenomenon termed"futile recanalization"(FR).Neuroinflammation plays a pivotal role in the pathological progression of IS and is closely associated with the development of FR.This systematic review synthesizes the pivotal role of neuroinflammation in FR,encompassing three core pathological mechanisms:the no-reflow phenomenon,cerebral ischemia-reperfusion injury,and the gut-brain axis.The identification of various inflammation-related biomarkers shows promise for early detection of high-risk FR patients.Therapeutic agents including TLR4 antagonists(e.g.ApTOLL),neuroprotective compounds,and traditional Chinese medicine formulations demonstrate treatment potential through modulation of neuroinflammatory pathways.Targeted interventions against neuroinflammation may emerge as a strategic approach to improve clinical outcomes in IS patients.

Objective To evaluate the clinical efficacy of hip-knee-ankle active and passive exercise therapy in patients with early-to mid-stage knee osteoarthritis(KOA).Methods A total of 180 patients with early to mid-stage knee osteoarthritis(KOA)were recruited from the First Affiliated Hospital of Hebei University of Tradi-tional Chinese Medicine between March 2023 and March 2024.Patients were randomly assigned to one of four groups:active movement group,passive movement group,combined movement group,and control group,with 45 patients in each group.The active movement group received hip-knee-ankle active movement therapy daily until the end of follow-up.The passive movement group underwent hip-knee-ankle passive movement therapy three times per week for two weeks.The combined movement group received both active and passive therapies.The control group was administered oral celecoxib capsules(200 mg once daily for two weeks).Joint function was assessed in all four groups before treatment,at two weeks post-treatment,and at 14 weeks post-treatment.The primary outcome measure was the WOMAC joint function score,while secondary outcomes included the WOMAC pain score,stiffness score,and quality of life score(SF-12).Results A total of 160 patients completed the trial,with 39 in the active group,42 in the passive group,40 in the combined group,and 39 in the control group.There were no significant differences in baseline characteristics among the groups(P>0.05).Compared to baseline,the WOMAC scores for function,pain,and stiffness in the passive,combined,and control groups decreased significantly at both 2 and 14 weeks post-treatment(P<0.05),while the SF-12 scores increased significantly(P<0.05).Between 2 and 14 weeks post-treat-ment,the active and combined groups showed further significant decreases in WOMAC function,pain,and stiffness scores(P<0.05)and increases in SF-12 scores(P<0.05).At 2 weeks post-treatment,compared to the control group,the passive and combined groups exhibited significantly lower WOMAC function scores(P<0.05),with no significant difference between the passive and combined groups(P>0.05).By 14 weeks post-treatment,the active and combined groups demonstrated significantly lower WOMAC function scores(P<0.05),with the combined group showing a significantly lower score than the active group(P<0.05).Conclusion The four therapeutic approaches demonstrate a certain degree of efficacy in improving joint function for patients with early and mid-stage KOA.The passive therapy group exhibits superior short-term outcomes,while the active therapy group shows better long-term benefits.The combined therapy group presents notable advantages in both short-term and long-term effi-cacy,although its short-term effectiveness does not surpass that of the passive therapy group.It is recommended for patients with early and mid-stage KOA who have underlying gastrointestinal and cardiovascular conditions.

Objective To investigate biological markers associated with psychotic symptoms in patients with bipolar disorder(BD)based on electronic medical records of patients,and to develop an interpretable risk prediction model that supports the identification of high-risk individuals and that facilitates decision-making for providing clinical intervention in a timely manner.Methods A total of 2 352 patients diagnosed with BD and admitted to West China Hospital,Sichuan University were enrolled using the electronic medical records system of the hospital.The participants were divided into two subgroups,the bipolar disorder depression(BDD)group and the bipolar disorder mania(BDM)group.The logistic regression algorithm was used to train and validate the prediction model,and interpretability methods were used to analyze the contribution of each feature to individuals and the effect of the features on specific target prediction decisions.Results The logistic regression model demonstrated robust predictive performance across the BD,BDD,and BDM cohorts,with areas under the curve(AUC)of the receiver operating characteristic curves always exceeding 81.6%.The core predictive features included platelet distribution width(PDW),fibrinogen(FIB),platelet large cell ratio(P-LCR),activated partial thromboplastin time(APTT),prothrombin time(PT),and triglyceride(TG).The logistic regression model exhibited strong interpretability and was combined with nomograms for intuitive risk quantification and individualized prediction.Conclusion The logistic regression model enables rapid and simple screening of BD patients with psychotic symptoms.Distinct patterns of changes observed in blood biomarkers of BDD and BDM subgroups enrich the understanding of the underlying pathophysiological mechanisms and highlight the importance of considering subtypes in the intervention and management of patients.

Over the years,the American Diabetes Association(ADA)has been actively committed to the development and promotion of standards for the diagnosis,treatment,and daily care of diabetes.Since 1989,it has updated the diabetes diagnosis and treatment standards every year,which have become one of the most authoritative guidelines in diabetes and have been recognized and adopted by various countries.On December 10,2024,the 2025 Standards of Care in Diabetes were released,incorporating the latest evidence-based medicine content related to diabetes and its complications and comorbidities.It aims to provide guidance on the diagnosis,treat-ment,and management of the condition for clinicians,patients and their families,and researchers.This article interprets the major up-dates from the Standards.

Objective To analyze temporal trends in infectious disease burden among Chinese elderly(≥60 years)using data from the Global Burden of Disease Study(GBD 2021),evaluate age-period-cohort effects on disease burden,predict trends through 2045,and propose evidence-based medication management strategies.Methods We conducted a threefold analysis of infectious disease burden from 1990 to 2021 using Joinpoint regression to identify temporal trends,Age-Period-Cohort(APC)modeling to disentangle epidemiological effects,and Nordpred projections for 2045 disease burden estimates.Results Over 32 years,all infectious disease categories except HIV/AIDS and sexually transmitted infections demonstrated significant declines.Enteric infections showed the most rapid reductions in mortality(AAPC=-7.85,P﹤0.001)and disability-adjusted life year rates(DALYR;AAPC=-7.18,P﹤0.001).We also found a significant decrease in the incidence of tropical diseases and malaria(AAPC=-6.77,P﹤0.001).APC analysis found that the age effect was mostly negative in terms of the annual percentage change in mortality and DALYR for each disease,except for HIV/AIDS,with an overall decline in period risk over time,and a generally higher risk of morbidity and mortality for the early birth cohort,and an overall decline in the risk of each disease as the year of birth progressed,but the risk of HIV/AIDS death and DALY period and cohort risks trended upward.While the overall risk for certain diseases was slightly higher in males compared to females,the trends were largely consistent across both sexes.In terms of projections,the absolute prevalence of respiratory infections and tuberculosis in terms of number of cases and age-standardized rates,and the growth of the disease burden of HIV/AIDS were particularly prominent,making them important health challenges for the future.The burden of disease in the elderly often results in issues such as potential polypharmacy,which must be addressed to improve medication management.Conclusions China has achieved remarkable progress in reducing infectious disease burdens among older adults,though HIV/AIDS and sexually transmitted infections present an escalating public health threat.These findings advocate for enhanced surveillance systems,age-specific prevention strategies,and precision medication protocols to optimize therapeutic outcomes in geriatric populations.

With the advancement of endovascular therapy(EVT)techniques,the recanalization rate for patients with ischemic stroke(IS)has exceeded 80%.However,more than 50%of patients fail to achieve favorable neurological outcomes following recanalization,a phenomenon termed"futile recanalization"(FR).Neuroinflammation plays a pivotal role in the pathological progression of IS and is closely associated with the development of FR.This systematic review synthesizes the pivotal role of neuroinflammation in FR,encompassing three core pathological mechanisms:the no-reflow phenomenon,cerebral ischemia-reperfusion injury,and the gut-brain axis.The identification of various inflammation-related biomarkers shows promise for early detection of high-risk FR patients.Therapeutic agents including TLR4 antagonists(e.g.ApTOLL),neuroprotective compounds,and traditional Chinese medicine formulations demonstrate treatment potential through modulation of neuroinflammatory pathways.Targeted interventions against neuroinflammation may emerge as a strategic approach to improve clinical outcomes in IS patients.

Objective:To determine the median effective dose (ED 50) and 95% effective dose (ED 95) of remimazolam for gastroscopy when combined with propofol in pediatric patients of different ages. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ pediatric patients, aged 3-12 yr, who underwent painless gastroscopy in Hainan Women and Children′s Medical Center from January to February 2024, were divided into the following groups: preschool group (3-6 yr) and school-age group (7-12 yr). Penehyclidine 0.01 mg/kg, afentanil 8 μg/kg and corresponding doses of remimazolam and propofol 1 mg/kg were intravenously injected, and gastroscopy was performed when the Modified Observer′s Assessment of Alertness/Sedation Scale score)≤1. Up-and-down sequential allocation was used. A positive response was defined as bucking, nausea, vomiting, body movement, and frowning occurred when the gastroscope entered the pharynx. The initial dose of remimazolam was 0.2 mg/kg, and the dose of remimazolam was increased/decreased by 0.02 mg/kg each time in the next patient. Probit regression method was applied to calculate the ED 50, ED 95 and 95% confidence interval ( CI) of remimazolam inhibiting responses to gastroscope placement when combined with propofol. The anesthesia-related adverse events were recorded. Results:A total of 27 pediatric patients completed the trial in preschool group and 26 cases in school-age group. The ED 50 of remimazolam was 0.266 mg/kg (95% CI 0.249-0.285 mg/kg) and the ED 95 was 0.302 mg/kg (95% CI 0.283-0.409 mg/kg) in preschool group. The ED 50 of remimazolam was 0.16 mg/kg (95% CI 0.147-0.170 mg/kg) and ED 95 was 0.183 mg/kg (95% CI 0.172-0.234 mg/kg) in school-age group. The ED 50 and ED 95 were significantly decreased in school-age group as compared with preschool group ( P<0.05). During anesthesia, 3 patients suffered hypotension (11%) in preschool group, and 3 patients suffered hypotension (12%), 2 patients suffered respiratory depression (8%), 2 patients suffered hiccup (8%), 1 patient suffered injection pain (4%) and 1 patient suffered muscle rigidity (4%) in school-age group. There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:When combined with propofol, the ED 50 of remimazolam for gastroscopy in preschool and school-age pediatric patients is 0.266 mg/kg and 0.160 mg/kg, respectively, and the ED 95 is 0.302 mg/kg and 0.183 mg/kg, respectively, indicating a stronger anesthetic potency in school-age children. The probability of adverse reactions is low when the two are combined.