ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

Objective:To analyze the prevalence of human respiratory syncytial virus（RSV）and the evolutionary characteristics of the adhesion glycoprotein（G）gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR；full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected，with 104 cases（4.08%，104/2 548）testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year（12.24%，18/147），and significant difference in positivity rates were found among age groups（χ 2=37.868， P<0.001）. Since October 2023，RSV has seen an epidemic peak during January to February 2024，and gradually declined thereafter，with no positive cases from May to September 2024. Among the 43 RSV-positive samples，12 strains were identified as subtype A（all genotype A.D.3），and 31 strains were subtype B（14 genotype B.D.4.1.1 and 17 genotype B.D.E.1）. Conclusion:From October 2023 to October 2024，RSV had an epidemic peak in January and February in Xi＇an，with subtype B being the predominant circulating type.

ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, with few effective treatments currently available. The multifactorial nature of AD, shaped by genetic, environmental, and biological factors, complicates both research and clinical management. Recent advances in artificial intelligence (AI) and multi-omics technologies provide new opportunities to elucidate the molecular mechanisms of AD and identify early biomarkers for diagnosis and prognosis. AI-driven approaches such as machine learning, deep learning, and network-based models have enabled the integration of large-scale genomic, transcriptomic, proteomic, metabolomic, and microbiomic datasets. These efforts have facilitated the discovery of novel molecular signatures and therapeutic targets. Methods including deep belief networks and joint deep semi-non-negative matrix factorization have contributed to improvements in disease classification and patient stratification. However, ongoing challenges remain. These include data heterogeneity, limited interpretability of complex models, a lack of large and diverse datasets, and insufficient clinical validation. The absence of standardized multi-omics data processing methods further restricts progress. This review systematically summarizes recent advances in AI-driven multi-omics research in AD, highlighting achievements in early diagnosis and biomarker discovery while discussing limitations and future directions needed to advance these approaches toward clinical application.

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

Osteoarthritis(OA),a common age-related chronic disease,is characterized by degenerative changes in the joints and surrounding tissues.Traditionally,research on OA has primarily focused on the pathological changes in articular cartilage and its repair.However,with the advancements in animal disease modeling in recent years,especially the widespread use of spatiotemporally specific transgenic mouse models,scholars have gradually come to realize that the subchondral bone also plays an important role in the occurrence and development of OA.That is,the pathological changes in articular cartilage and bone mutually affect and promote each other,jointly driving the progression of OA,involving such pathological processes as vascular invasion,ectopic calcification,nerve growth,and the occurrence of pain.Given the complexity of cartilage-bone pathological relationship,it is difficult to conduct in-depth research on subchondral bone pathology using clinical human samples,or to simulate the pathological processes of OA through in vitro cell experiments.Therefore,animal models play an irreplaceable role in investigating the pathological mechanisms of OA and developing clinical drugs.This review,in addition to providing an overview of OA animal models,synthesizes the latest progress in animal experimental research on OA,highlighting the active role of the cartilage-bone pathological relationship in OA progression.These new findings provide references for future in-depth investigations and also provide a theoretical basis for developing fundamental strategies for OA prevention and treatment.

Objective:To explore the optimal age cutoff for diagnosis and the prognosis of early-onset gastric cancer in young patients.Methods:Clinicopathological data of patients with gastric adenocarcinoma aged ≤45 years who had undergone radical gastrectomy in the Department of Gastric Surgery, Fudan University Shanghai Cancer Center from January 2013 to December 2018 were retrospectively collected. Patients with distant metastases, other malignant tumors, combined organ resection, gastric stump cancer, positive margin, and incomplete clinical or follow-up data were excluded. X-tile software analysis of the actual overall survival of the collected cases yielded an optimal cut-off of 32 years. Accordingly, the enrolled cases were divided into an early-onset young group (age ≤32 years) and young adult group (age >32 years). Clinicopathological characteristics, long-term survival, and postoperative recurrence were compared between the two groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model to identify the factors affecting the prognosis of young patients with gastric cancer.Results:The study cohort comprised 462 patients, including 256 (55.4%) women, 419 (90.7%) with middle and lower gastric cancers, and 343 (74.2%) with poorly differentiated tumors. There were 101 patients in the early-onset young group and 361 in the young adult group. These groups did not differ significantly in terms of sex, body mass index, tumor location, tumor size, surgical procedure, neurovascular invasion, or tumor stage (all P>0.05). The proportion of patients with poorly differentiated tumors in the early-onset young group was significantly higher than that in the young adult group (89.1%[90/101] vs. 70.1%[253/361], χ 2=15.26, P<0.001). All study patients completed 5 years of follow-up, the median duration of which was 101 months (61-133 months). Death or tumor recurrence occurred in 151 patients (32.7%), in 118 of whom the sites of recurrence and metastasis could be identified, 38 in the early-onset young group and 80 in the young adult group. Fifty-five (46.6%) patients developed peritoneal metastases and 40 (33.9%) hematogenous metastases. In the early-onset young group, 20 patients developed peritoneal metastases, 11 hematogenous metastases, five distant lymph node metastases, and two local recurrence. In the young adult group, 35 patients developed peritoneal metastases, 29 hematogenous metastases, six local recurrences, and 10 distant lymph node metastases. The 5-year overall survival and disease-free survival rates were significantly higher in the young adult group than in the early-onset young group (73.7% vs. 57.4%, P=0.002 and 70.6% vs. 55.4%, P=0.004, respectively). Cox multivariate analysis showed that age >32 years (HR=0.63, 95%CI: 0.43-0.90, P=0.012) was an independent protective factor for overall survival, whereas later N stage (HR=1.67, 95%CI:1.09-2.57, P=0.018) was an independent risk factor for overall survival after surgery ( P<0.05). Age >32 years (HR=0.60, 95%CI: 0.41-0.86, P=0.006) was also an independent protective factor for disease-free survival, whereas later N stage was an independent risk factor (HR=1.69, 95%CI: 1.08-2.64, P=0.021). Conclusion:Young patients with early-onset gastric cancer aged ≤32 years have worse tumor differentiation and prognosis.

BACKGROUND: Lung cancer is one of the malignant cancers with the highest incidence rate, and it is important to identify the factors contributing to lung cancer carcinogenesis for prevention. Lifestyle and genetic factors play important roles in cancer development, however the impact of dietary factors, such as soy product intake, on lung cancer risk remains inadequately understood. This study aims to explore the associations between soy product intake, genetic risk, and lung cancer incidence, and validate the consistent effects of soy product intake in European populations, thereby providing new insights for lung cancer prevention. METHODS: Utilizing the Shanghai Suburban Adult Cohort and Biobank (SSACB) (n=66,311), Cox proportional hazards model was adopted to assess the association between soy product intake and lung cancer incidents, followed by subgroup analyses stratified by gender, smoking status, and pathological types of lung cancer. The UK Biobank (UKB) was used for validation of the effect of soy product intake on lung cancer. To investigate the association between genetic factors and lung cancer, in addition to previously reported loci, we incorporated newly identified loci from two independent studies in Southeast China: a nested case-control population from the SSACB cohort (433 cases/650 controls) and a case-control study from the Shanghai Cancer Center-Taizhou cohort (1359 cases/1359 controls). Meta-analysis and Linkage disequilibrium clumping (LD clumping) of the association results identified 23 loci for polygenic risk score (PRS) construction. Subsequently, conditional Logistic regression model was used to assess the association between genetic risk and lung cancer. RESULTS: In SSACB cohort, after adjusting for age, gender, smoking, chronic bronchitis, body mass index (BMI), vegetable intake and red meat intake, sufficient soy product intake was significantly associated with a reduced risk of lung cancer [hazard ratio (HR)=0.60, 95%CI: 0.47-0.77, Padj=6.69E-05], an effect that was consistent in males and females, smokers and non-smokers. In UKB, although the association did not reach statistical significance, a protective trend against lung cancer was also observed (HR=0.76, 95%CI: 0.55-1.06, Padj=0.10). In the nested case-control population within SSACB, a PRS score generated in the Chinese population was significantly correlated with lung cancer risk. After adjustment of age, gender, smoking, chronic bronchitis, and soy product intake, the high-PRS group had a 1.88 times higher risk of lung cancer compared to the low-PRS group (Padj=1.84E-03). CONCLUSIONS The prospective cohort study found that adequate intake of soy products was significantly associated with a reduced risk of lung cancer, while a high PRS is a risk factor for lung cancer development. Integrating soy product intake and PRS into traditional epidemiological risk factor prediction will guide personalized lung cancer prevention and high-risk population stratification.
Humans ; Lung Neoplasms/etiology* ; Male ; Female ; China/epidemiology* ; Middle Aged ; Adult ; Aged ; Prospective Studies ; Biological Specimen Banks ; Risk Factors ; Case-Control Studies ; Cohort Studies

Objective:To investigate the intervention effect of five elements music of traditional Chinese medicine and western classical music on the sleep quality of stroke patients, and to compare the difference between the two, to provide a reference for the clinical care measures to improve the sleep quality of stroke patients.Methods:By adopting a randomized controlled trial, 75 stroke patients who were hospitalized in the rehabilitation hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2022 to July 2023 were selected by convenience sampling method as the study subjects, and the patients were randomly divided the conventional treatment group, the five-element music group, and the classical music group according to the method of randomized numerical table with 25 cases in each group. On the basis of general treatment, the conventional treatment group took sleep health education, the five elements music group were given five-element music intervention based on conventional treatment, and the classical music group were given classical music intervention based on conventional treatment. The changes of Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) examination parameters in the 3 groups were compared.Results:There were 2 cases of shedding in the conventional treatment group, and 23 cases were finally included, 15 males and 8 females, aged (54.02 ± 7.80) years; there were no cases of shedding in the five-element music group, and 25 cases were finally included, 12 males and 13 females, aged (53.69 ± 6.02) years; and there was 1 case of shedding in the classical music group, and 24 cases were finally included, 10 males and 14 females, aged (52.34 ± 7.08) years. Comparison of AIS, PSQI and PSG scores among the 3 groups of patients before intervention showed no statistically significant differences (all P>0.05). After the intervention, the AIS scores and PSQI scores of the 3 groups were (9.48 ± 1.53) and (12.22 ± 2.94), (6.76 ± 1.36) and (7.64 ± 2.08), (7.46 ± 1.38) and (10.33 ± 2.82), respectively, and the differences were statistically significant ( F=23.21, 18.44, both P<0.05). PSG sleep structure parameters showed that the total sleep time, REM latency time and sleep efficiency of the patients in the five-element music group after the intervention were (399.89 ± 51.76) min, (136.26 ± 25.36) min, (78.87 ± 8.21)%, higher than (368.45 ± 47.88) min, (124.46 ± 26.25) min, (73.36 ± 7.86)% in the classical music group and (345.48 ± 38.69) min, (111.37 ± 23.23) min, (69.44 ± 7.88)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=8.27, 5.93, and 8.49, all P<0.05); the sleep latency time, awakening time, and number of awakenings in the five-element music group were (28.86 ± 17.68) min, (54.37 ± 25.15) min, and (2.72 ± 1.19) times, respectively, which were lower than those in the classical music group (35.67 ± 16.99) min, (64.28 ± 29.34) min, and (3.67 ± 1.12) times and (42.38 ± 18.96) min, (78.38 ± 37.26) min, (4.87 ± 1.46) times in the conventional treatment group, and the differences between three groups were statistically significant ( F=3.51, 3.66, and 17.56, all P<0.05). The results of the PSG sleep progression showed that the duration of the N1 stage of sleep in the five-element music group after the intervention was (95.71 ± 15.23) min, which was higher than (83.20 ± 18.34) min in the classical music group and (80.93 ± 16.47) min in the conventional treatment group, and the difference between three groups was statistically significant ( F=5.53, P<0.01); the N3 stage sleep time and the sleep percentage of the five-element music group after the intervention were respectively (84.23 ± 20.98) min and (23.98 ± 5.89)%, which were higher than (65.33 ± 18.82) min and (18.34 ± 3.78)% in the classical music group and (45.87 ± 18.65) min and (15.03 ± 5.56)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=23.08, 18.50, both P<0.05). Conclusions:Both five elements music and classical music can improve the sleep quality of stroke patients, and the effect of five elements music to improve sleep is more significant.