Objective To investigate the current status of cognitive impairment and its influencing factors in patients with Alzheimer's disease (AD) and to explore effective intervention strategies. Methods A total of 380 patients with AD diagnosed in the Qingdao Central Hospital were retrospectively enrolled between January 2023 and January 2025. According to scores of Montreal Cognitive Assessment (MoCA), the patients were divided into a mild cognitive impairment group (21-25 points) and a moderate to severe impairment group (<21 points). The general clinical data in the two groups were collected. The influencing factors of moderate to severe cognitive impairment were analyzed by univariate and multivariate logistic regression analysis. Results Among the 380 AD patients, 157 cases (41.32%) had mild cognitive impairment, and 223 cases (58.68%) had moderate to severe cognitive impairment. Compared with the mild cognitive impairment group, the moderate to severe cognitive impairment group had a higher proportion of patients who were aged ≥ 75 years, engaged in physical labor, had a disease course of ≥5 years, and had moderate to severe atrophy on head CT examination (P < 0.05). Age ≥75 years, disease course ≥5 years, and moderate to severe atrophy on head CT were independent risk factors of moderate to severe cognitive impairment in AD patients (P<0.05). Conclusion Cognitive impairment is closely related to age, disease course and head CT manifestations in AD patients. Interventions targeting these key factors are expected to delay cognitive decline and improve patients' quality of life.

Background: and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods: This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results: Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

ObjectiveTo observe the clinical efficacy and safety of lung-boosting moxibustion with different moxibustion doses in the treatment of stable chronic obstructive pulmonary disease （COPD）. MethodsA total of 240 stable COPD patients with lung qi deficiency， lung-spleen qi deficiency， or lung-kidney qi deficiency syndrome were enrolled， all receiving standardized western medical treatment and lung-boosting moxibustion. According to the thickness of the moxa wool， the thickness of the ginger paste， and the treatment duration， patients were randomly divided into eight groups， which were Group A （3.0 cm thickness moxa， 2.5 cm ginger mud， 60 min treatment time）， Group B （3.0 cm thickness moxa， 2.5 cm ginger mud， 90 min treatment time）， Group C （2.0 cm thickness moxa， 2.5 cm ginger mud， 60 min treatment time）， Group D （2.0 cm thickness moxa， 2.5 cm ginger mud， 90 min treatment time）， Group E （3.0 cm thickness moxa， 2.0 cm ginger mud， 60 min treatment time）， Group F （3.0 cm thickness moxa， 2.0 cm ginger mud， 90 min treatment time）， Group G （2.0 cm thickness moxa， 2.0 cm ginger mud， 60 min treatment time）， Group H （2.0cm thickness moxa， 2.0cm ginger mud， 90 min treatment time）. Treatment was performed once every 15 days for 3 months， with a total of six sessions. The primary outcomes were the scores of the clinical symptoms and signs questionnaire for stable COPD before and after treatment， comprising seven symptom domains （cough， sputum production， wheezing， chest tightness， shortness of breath， fatigue， and cyanosis） and the total score. The secondary outcomes included the scores of the modified COPD patient-reported outcome questionnaire （mCOPD-PRO） involving the physical， psychological， and environmental domains and the total score， the scores of the modified Effectiveness Satisfaction Questionnaire for COPD （mESQ-COPD） involving clinical symptoms， work and daily living capacity， environmental adaptability， treatment efficacy， and the total score before and after treatment， the moxibustion sensation scores （heat sensation score and special sensation intensity score） during treatment， and cutaneous temperature （the maximum temperature achieved， the duration of temperature maintained at ≥43 ℃， and the time required to reach 43 ℃）. The safety evaluation was carried out after treatment. ResultsDuring the study， 18 patients withdrew， and 222 patients were included in the per-protocol set for analysis， including 27 in Group A， 28 in Group B， 28 in Group C， 29 in Group D， 27 in Group E， 28 in Group F， 27 in Group G， and 28 in Group H. After treatment， the total score on the clinical symptoms and signs questionnaire， as well as the cough and chest tightness symptom scores in Group F were significantly lower than those in other groups （P＜0.05）. Group F demonstrated statistically lower total mCOPD-PRO score and physical domain score （P＜0.05）， lower total mESQ-COPD score and the scores for clinical symptoms and treatment efficacy （P < 0.05）， as well as higher heat sensation score （P＜0.05） than other groups. The maximum temperature was significantly higher in Group E and Group F than in the other groups， while the duration of temperature maintained at ≥43 ℃ was significantly longer in Group F than other groups， and the time required to reach 43 ℃ was significantly shorter in Group E and Group F than in Groups C， D， G， and H （P＜0.05）. No significant abnormalities were observed in routine blood tests， liver function， renal function， urinalysis， or electrocardiograms before and after treatment in any group. No serious adverse events occurred during the treatment period. ConclusionThere are differences in the efficacy of different moxibustion doses of lung-boosting moxibustion in the treatment of stable COPD. Moxibustion with 3.0 cm thickness moxa， 2.0 cm ginger mud， and 90 min treatment time can obtain relatively superior efficacy while demonstrating a favorable safety profile.

Eleven sesquiterpenoids were isolated from the petroleum ether and ethyl acetate extracted fraction of 95% ethanol extract of fresh Centipeda minima by using modern chromatographic separation techniques such as silica gel, MCI, gel, and semi-preparative liquid chromatography. Their structures were identified using spectroscopy and nuclear magnetic resonance(NMR) calculation as minimin A(1), brevilin A(2), minimolide L(3), minimolide A(4), minimolide B(5), arnicolide D(6), microhelenin C(7), 2β-hydroxyl-2,3-dihydrogen-6-O-angeloylplenolin(8), 11α,13-dihydroarnifolin(9),(1S,2R,5R,6S,7S,8S,10R)-6-hydroxy-2-ethoxy-4-oxopseudoguai-11(13)-en-12,8-olide(10), and pulchellin-2-O-isovalerate(11), among which compound 1 was a new compound, and compounds 9-11 were isolated from Centipeda for the first time. The evaluation results of in vitro anti-inflammatory activity showed that compounds 1-11 possessed significant anti-inflammatory activity, with IC_(50) values ranging from(0.13±0.03) to(13.11±0.17) μmol·L~(-1).
Sesquiterpenes/pharmacology* ; Animals ; Asteraceae/chemistry* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Macrophages/immunology*

Objective: To investigate the changing trends for associations of anxiety and depressive symptoms with smartphone addiction among middle school students, so as to provide a scientific basis for preventing smartphone addiction in middle school students. Methods: From 2022 to 2023, a method of combining convenient sampling with cluster sampling was used to select 8 923 middle school students from 27 junior high schools and 3 senior high schools in a district of Shenzhen City between September 2022 (baseline, T1) and September 2023 (follow up, T2). The Smartphone Addiction Scale-Short Version (SAS-SV), Patients Health Questionnaire-9 Item (PHQ-9), and Generalized Anxiety Disorder 7-item Scale (GAD-7) were administered to assess smartphone addiction, anxiety and depressive symptoms. Mixed effects models were used to analyze the association of anxiety and depressive symptoms with smartphone addiction among middle school students. Results: From September 2022 to September 2023, the reported prevalence of smartphone addiction increased from 24.22% to 25.25% ( χ 2=45.71); and smartphone addiction scores [ 24.00 (16.00, 32.00),25.00(16.00, 33.00)], anxiety symptom scores [2.00(0.00, 7.00),3.00(0.00, 7.00)] and depressive symptom scores[3.00(0.00, 8.00),5.00(0.00, 9.00)] all significantly increased ( Z =-17.43, -42.38, -41.57) (all P <0.05). There were statistically significant difference in the distribution of anxiety and depression symptom levels among middle school students in 2022 and 2023 ( χ 2=85.15, 106.85, both P <0.05). After adjusting for covariates such as age, gender and family background, mixed effects models revealed dose response associations of anxiety and depressive symptoms with smartphone addiction among middle school students:mild anxiety symptom( OR =3.22), moderate to severe anxiety symptom ( OR =5.36), mild depressive symptom ( OR =3.32) and moderate to severe depressive symptom ( OR =6.13) were significantly associated with higher risks of smartphone addiction (all P <0.05). Interaction effect analysis found that co existing anxiety and depressive symptoms synergistically increased addiction risk by 5.60 times ( OR =5.60) compared to the asymptomatic group, with 32% of the combined risk attributable to their interaction ( S=1.64, AP =0.32)(both P < 0.05 ). Conclusions Anxiety and depressive symptoms are significantly associated with smartphone addiction, exhibiting a synergistic effect. Attention should be paid to emotional issues and smartphone addiction among middle school students.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

Objective To evaluate the efficacy of Compound Fipronil Spot-on Solution in repelling canine ticks.Methods A total of 140 dogs infested with ticks were randomly selected from regions in southern and northern China and assigned to four groups:southern test drug group,southern control drug group,northern test drug group,and northern control drug group.Each group comprised 35 dogs.Each dog was administered the prescribed dose.The number of ticks was counted on days 1,7,14,21,and 28 following the administration.The negative conversion and average reduction rates of the tick population were then subjected to statistical analyse.Results The mean efficacy of the test drug was 100%in both the southern and northern cohorts,28 days post-treatment.The control drug showed comparable efficacy,reaching a mean reduction of 100%in both regions by the same time point.No additional clinical manifestations or adverse events were observed across all treated dogs.Conclusions Compound Fipronil Spot-on Solutions effectively treats and prevents ticks in dogs in different regions of China.A single dose remains effective for up to 28 days,thus providing a convenient,effective solution.

ObjectiveTo investigate the relationship between the composition of traditional Chinese medicine (TCM) and depression/anxiety/sleep disturbances (D/A/S) in patients with chronic pain.MethodsThis cross-sectional study was conducted at 13 tertiary hospitals across China, enrolling patients who experienced chronic pain between November 2023 and May 2024. The Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Pittsburgh Sleep Quality Index, and TCM constitution categories were used to assess the patients. The association between the TCM constitution and the D/A/S ratio was analyzed using multivariable logistic regression.ResultsA total of 1107 patients (63.2% women) were analyzed. Compared with those with a balanced constitution, patients who had qi-deficiency and yin-deficiency were at a higher risk of depression. Qi-deficiency and yin-deficiency were associated with anxiety. Sleep disturbances were common in patients with qi-deficiency constitution (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.42–3.81), yang-deficiency constitution (OR: 1.94, 95% CI: 1.26–2.98), yin-deficiency constitution (OR: 2.03, 95% CI: 1.24–3.32), blood stasis constitution (OR: 2.07, 95% CI: 1.01–4.22), and qi-stagnation constitution (OR: 2.66, 95% CI: 1.35–5.25).ConclusionIn patients with chronic pain, specific TCM constitutions may be associated with D/A/S. Further longitudinal studies are needed to clarify the potential causal relationships between TCM constitution types and these conditions.