OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

Objective To investigate the regulatory mechanism of the central nervous system in patients with refractory overactive bladder (rOAB) using diffusion tensor imaging (DTI) and graph theory analysis. Methods A total of 43 rOAB patients (rOAB group) and 46 matched healthy controls (HC group) were recruited during May and Nov.2024. All participants were scanned with DTI, and surveyed with the overactive bladder symptom score (OABSS), and overactive bladder questionnaire (OAB-q). Their age, gender, height, weight, and educational years were collected.DTI plus graph theory analysis was employed to explore the alterations in global and local topological properties of the brain structural network in rOAB patients. Brain regions showing significant group differences in structural metrics [specifically, the right paracentral lobule (PCL.R) ]were further used as seed points for functional connectivity (FC) analysis. Correlations between the nodal clustering coefficient (NCp) of the identified region, FC strength, OABSS, and OAB-q score were investigated. Results The OABSS [8 (6,10) vs.0 (0,1) ]and OAB-q [71 (53,80) vs.20 (19,24) ]were higher in the rOAB group than the HC group (P<0.001). Graph theory analysis revealed no statistically significant differences in global network metrics between the two groups (P>0.05). However, the NCp was significantly higher in the PCL.R of rOAB group compared to HC group (P<0.05, FDR-corrected).FC analysis using the PCL.R as a seed region demonstrated significantly reduced FC value in the left cerebellar crus Ⅱ (Cerebelum_Crus2_L) of the rOAB group (P<0.05, FDR-corrected). Partial correlation analysis showed that the NCp of PCL.R was positively correlated with both OABSS (r=0.255, P=0.018) and OAB-q score (r=0.257, P=0.017). Conversely, the FC of Cerebelum_Crus2_L was significantly negatively correlated with OABSS (r=-0.545, P<0.001) and OAB-q score (r=-0.535, P<0.001). Conclusion Patients with rOAB exhibit distinct brain structural network alterations compared to healthy individuals, primarily manifestation in the NCp value of PCL.R increased, and the FC intensity of Cerebelum_Crus2_L is significantly weakened. These alterations in the topological properties of the structural network may be implicated in the pathogenesis of rOAB.

Objective:To investigate the effect of dandelion polysaccharide(DP)on inflammatory response and the protein expression of S100 calcium binding protein A8/A9(S100A8/A9)in lung tissue and small intestinal tissue of rats with multiple organ dysfunction syndrome(MODS).Methods:The two-hit method of hemorrhagic shock and intraperitoneally injected lipopolysaccharide was used to establish a rat model of MODS,and the rats were divided into sham-operation group,model group,low-dose DP group,and high-dose DP group.The organ coefficient and wet/dry weight ratio of the lung and the small intestine were observed for each group of rats;HE staining was used to observe the pathomorphological changes of lung tissue and small intestinal tissue;immunohistochemical staining was used to measure the expression of interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-10(IL-10)in lung tissue and small intestinal tissue;Western blot was used to measure the protein expression level of S100A8/A9 in lung tissue and small intestinal tissue.Results:Compared with the sham-operation group,the model group had significant increases in the organ coefficient of the lung(5.849±0.824),the wet/dry weight ratio of the lung(6.556±0.631),the wet/dry weight ratio of the small intestine(6.356±0.535),and the wet weight/length ratio of the small intestine(73.950±5.569).HE staining showed that that the model group had massive in-flammatory cell infiltration in alveolar space and pulmonary interstitium,thickened alveolar wall,and disintegration and fragmentation of the villi of the small intestine,with inflammatory cell infiltration and proliferation of segmental aggregated lymphoid follicles.In the model group,S100A8/A9 was mainly expressed in neutrophils and macrophages,and there were increases in the expression of S100A8/A9,IL-1β,and IL-6 and a reduction in the expression of IL-10 in the lung tissue and small intestinal tissue of rats.After treatment with high-dose DP,there were reductions in the organ coefficient of the lung(4.297±0.462),the wet/dry weight ratio of the lung(5.313±0.495),the wet/dry weight ratio of the small intestine(5.398±0.388),and the wet weight/length ratio of the small intestine(59.417±2.891).The high-dose group also had alleviation of pathological injury in the small intestine,with reductions in the expres-sion of S100A8/A9,IL-1β,and IL-6 and an increase in the expression of IL-10 in lung tissue and small intestinal tissue.Conclusion:DP may alleviate inflammatory response in lung and small intestinal injuries of rats with MODS by inhibiting the expression of S100A8/A9.

Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

Objective:To analyze the epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia and explore the related factors of these two health problems.Methods:In September 2022, a stratified random cluster sampling method was employed to select 188 635 children and adolescents aged 6-18 in Inner Mongolia for physical examinations and questionnaire surveys. Data on height, weight, as well as dietary behavior, physical activity, classroom environment, academic tasks, writing posture, and screen behavior were collected. The epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity were analyzed. Additionally, a multivariate logistic regression model was used to analyze the factors associated with wasting, spinal curvature abnormalities and multimorbidity.Results:A total of 188 635 children and adolescents aged 6-18 years participated in this study, including 95 393 boys (50.6%) with an average age of (11.53±3.32) years. The detection rate of wasting was 3.79%, with a higher detection rate in boys (4.18%) than in girls (3.38%) ( P<0.001). The detection rate of spinal curvature abnormalities was 3.64%, with a higher detection rate in girls (4.04%) than in boys (3.25%) ( P<0.001). The detection rate of multimorbidity between wasting and spinal curvature abnormalities was 0.17%, and there was no statistically significant difference between genders ( P>0.05). The detection rates of wasting, spinal curvature abnormalities, and multimorbidity all increased with age ( P t<0.001). The multivariate logistic regression analysis showed that, after adjusting for gender, age, urban/rural status, and school grade, compared to children and adolescents who exercised ≥1 hour of moderate-to-vigorous physical activity (MVPA) for at least 5 days per week and had daily screen time <2 hours, those who exercised <5 days per week ( OR=1.28, 95% CI: 1.19-1.37) and had daily screen time ≥2 hours ( OR=1.11, 95% CI: 1.03-1.19) had a higher risk of wasting. Compared to children and adolescents who had ≥5 physical education (PE) classes per week, adjusted desk and chair height,<1 hour of after-school study/writing time, and whose parents or teachers rarely or never reminded them about posture, those with <5 PE classes per week ( OR=1.11, 95% CI: 1.02-1.21), unadjusted desk and chair height ( OR=1.08, 95% CI: 1.01-1.15),≥1 hour of after-school study/writing time ( OR=1.15, 95% CI: 1.07-1.24), frequent reminders from parents ( OR=1.16, 95% CI: 1.09-1.23), and frequent reminders from teachers ( OR=1.10, 95% CI: 1.04-1.16) had a higher risk of spinal curvature abnormalities. Compared to children and adolescents who did not consume sugary drinks daily, exercised ≥1 hour of MVPA for at least 5 days per week, and whose teachers rarely or never reminded them about posture, those who consumed sugary drinks daily ( OR=1.61, 95% CI: 1.00-2.46), exercised <5 days per week ( OR=1.33, 95% CI: 1.01-1.79), and had teachers who frequently reminded them about posture ( OR=1.35, 95% CI: 1.05-1.75) had a higher risk of multimorbidity between wasting and spinal curvature abnormalities. Conclusion:The detection rates of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia are generally low, with an increasing trend observed with age. Both lifestyle and school environmental factors are associated with wasting, spinal curvature abnormalities and multimorbidity.

ObjectivesTo summarize the clinical and pathological features of patients with congenital liver fibrosis （CHF）， and to investigate the differences in clinical and pathological features between patients in different age groups. MethodsA retrospective analysis was performed for the clinicopathological data of 26 patients with pathologically confirmed CHF in China-Japan Friendship Hospital from August 2005 to June 2023， and the patients were stratified by age to investigate the clinical and pathological features of patients in different age groups. ResultsAmong the 26 patients， there were 12 male patients and 14 female patients， with an age of onset of 4 — 61 years. There were 19 patients with portal hypertension type （73.08%）， 2 patients with cholangitis type （7.69%）， 4 patients with mixed type （15.38%）， and 1 patient with occult type （3.85%）. Of all 26 patients， 4 had unknown clinical symptoms， and among the 22 patients with clear clinical symptoms， 10 （45.45%） attended the hospital due to upper gastrointestinal bleeding caused by portal hypertension. Pathological manifestations included roughly normal liver parenchyma separated by fibrous septa in the portal area， with the presence of abnormal reactive bile duct hyperplasia. Denser fibrous septa and a lack of portal veins with the corresponding caliber were observed in 4 pediatric patients with disease onset before the age of 10 years， with a significant reduction or even disappearance of compensatory thin-walled blood vessels. ConclusionPortal hypertension-type CHF is the most common type in clinical practice. Patients with an early age of onset have certain histopathological features of the liver， with the presence of serious complications associated with portal hypertension. Therefore， liver biopsy should be performed for patients suspected of CHF in clinical practice， and genetic testing should be performed when necessary. Early identification and diagnosis are of great importance for improving the prognosis of patients.

Objective: To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.

Objective: To explore the longitudinal association between only-child status and smartphone addiction among middle school students, so as to provide a basis for establishing family intervention measures for smartphone addiction in middle school students. Methods: In October 2022 and October 2023, a preliminary survey and follow-up were conducted among 8 759 middle and high school students from 30 schools in a district of Shenzhen. A self-designed questionnaire was used to determine whether the students were the only-child, and the Chinese Version of the Smartphone Addiction Scale-Short Version (C-SAS-SV) was utilized to assess the students smartphone addiction status. A multilevel mixed-effects model and subgroup analysis were applied to examine the association between only-child status and smartphone addiction among middle school students. Results: During 2022 to 2023, the prevalence of smartphone addiction in the cohort of middle school students increased from 24.1% to 25.2%. Compared with only-child, non-only child were more likely to be addicted to smartphones (adjusted model: OR =1.2, 95% CI =1.1-1.4) and also scored higher on smartphone addiction (adjusted model: β =0.9, 95% CI =0.2-1.5)( P <0.05). Subgroup analysis further revealed that compared to baseline, non-only child demonstrated an increased prevalence of smartphone addiction (adjusted model: OR = 1.2 , 95% CI =1.0-1.5) and higher addiction scores (adjusted model: β =0.8, 95% CI =0.2-1.5) after one year( P <0.05). Conclusions Non-only child face higher risk of smartphone addiction. Under the current population policy, it is crucial to address smartphone addiction among middle school students who is not only child.

Chinese medicine intestinal administration(CMIA)can avoid the degradation of drugs in gastric acid,bypass the first-pass effect of the liver,and deliver drugs directly to the lesion site.This approach increases local drug concentration,reduces drug dosage,and enhances bioavailability.This study systematically introduces the advantages,drug dosage forms,and whole-colon deliv-ery technologies of CMIA for treating UC,and reviews its mechanisms of action,including repairing intestinal epithelial layer and mu-cous layer,regulating the intestinal microbiota,improving immune function,and promoting local blood circulation.It also analyzes the current progress and limitations of research,aiming to provide a more solid theoretical basis for the treatment of UC with Chinese medi-cine and to offer references for the development of UC therapeutic drugs and administration methods.