ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

Oral squamous cell carcinoma (OSCC), the most common type of head and neck malignancy, has a poor prognosis owing to its high invasiveness and high rate of cervical lymph node metastasis. The tumor microenvironment (TME) is a complex microenvironment that is essential for tumor cell survival. Tumor-associated immune cell (TAIC), the main stromal cell of TME, regulates the proliferation, invasion, epithelial-mesenchymal transformation (EMT), and anti-tumor immunity of OSCC. M2-tumor-associated macrophages (TAMs) promote the invasion and metastasis of OSCC through the macrophage migration inhibitory factor/NOD-like receptor family pyrin domain containing 3/interleukin (IL)-1β axis, while N2-tumor-associated neutrophils (TANs) regulate the proliferation and EMT of OSCC through the Janus kinase 2/signal transducer and activator of transcription 3 pathway. Meanwhile, myeloid-derived suppressor cells (MDSCs) accelerate the progression of OSCC by secreting IL-6, IL-10, and transforming growth factor (TGF)-β; T cells promote inflammation by secreting IL-17 and inhibit inflammation-mediated tumor immune response by secreting IL-10 and TGF-β; and natural killer (NK) cells recognize and attack OSCC cells to inhibit OSCC progression. TAIC interaction network also regulates OSCC progression. M2-TAMs regulate the invasion and metastasis of OSCC by promoting T cell apoptosis through the secretion of IL-10 and programmed death-ligand (PD-L) -1, while N2-TANs inhibit T cell proliferation and cytotoxicity by secreting LOX-1 and arginase-1. MDSCs inhibit the proliferation and anti-tumor effects of CD8+ T cells through the inactivation of programmed cell death (PD)-1/PD-L1 signaling. Additionally, MDSCs inhibit the proliferation of T cells by decreasing the expression of the CD3-zeta chain and interferon-γ (IFN-γ). Moreover, tumor-infiltrating lymphocytes and NK cells were found to be positively correlated in OSCC progression. Therefore, target regulation, related signaling pathways, and the interaction network of TAIC may serve as promising therapeutic targets in the immunotherapy of OSCC. In this review, we summarize the recent research on the effects of TAIC and their interaction network in the TME in the progression of OSCC and explore its application in the early diagnosis and treatment of OSCC

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

OBJECTIVES: This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC. METHODS: The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model. RESULTS: LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor. CONCLUSIONS LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Animals ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness ; Cell Proliferation ; Mice, Nude ; Cell Movement ; Lysosomal Membrane Proteins/genetics* ; Mice ; Cell Line, Tumor ; Neoplasm Metastasis

BACKGROUND:Cervical instability is a common orthopedic disease in young and middle-aged people,and is the early manifestation of cervical spondylosis,which has a great impact on the quality of life of patients.Therefore,early diagnosis of cervical instability to implement early intervention has positive clinical and social significance.OBJECTIVE:The clinical prediction model of cervical instability in young and middle-aged people was constructed based on machine learning to realize early screening of cervical instability in young and middle-aged people before X-ray examination.METHODS:From September 2022 to October 2023,155 young and middle-aged adults with cervical instability and 88 with non-cervical instability recruited through recruitment advertisements and spinal department outpatient of Wangjing Hospital,China Academy of Chinese Medical Sciences were selected as research subjects.The research subjects'general information,living and working habits,discomfort symptoms,visual analog scale score,Neck Disability Index,and 36-ltem Short Form Health Survey were collected on site based on questionnaires.The above information was used as predictive factors.After screening,six machine learning algorithms of Support Vector Machine,LightGBM,RandomForest,Logistic,AdaBoost,and XGBClassifier were used to train the model by ten-fold cross-validation method,and the clinical prediction model of cervical instability was constructed.Area under the curve was used as the main evaluation index.Univariate analysis was performed on the predictors,and SHAP method was used to rank the importance of the predictors.Correlation heat maps were used to show the degree of linear correlation between the predictors and the cervical instability.RESULTS AND CONCLUSION:(1)Among the six machine learning models,RandomForest model was chosen as the final prediction model,including nine predictors,such as age,body mass index,neck circumference/neck length,visual analog scale score,Neck Disability Index,bodily pain,general health,vitality,and mental health,area under the curve=0.725 4,and the calibration degree was good.It could be used as a reference tool for early screening of cervical instability in young and middle-aged people.(2)There were significant differences in age,visual analog scale score,Neck Disability Index,bodily pain,general health,and vitality between the two groups(P＜0.05).(3)The order of importance of predictors was age,Neck Disability Index,visual analog scale score,general health,body mass index,vitality,bodily pain,neck circumference/neck length,mental health,among which age,visual analog scale score,Neck Disability Index were positively correlated with cervical instability,while general health,body mass index,vitality,bodily pain,neck circumference/neck length,and mental health were negatively correlated with cervical instability.

Objective:To explore the application effect of BOPPPS teaching model in the teaching of Food Safety Supervision and Management course.Methods:Students of two parallel classes majoring in the Food Quality and Safety of the same grade of a university in Liaoning Province were selected,and the traditional teaching model and BOPPPS teaching model were used for teaching practice respectively.The scores,teaching effect and satisfaction of two groups were compared.Results:The regular performance and total scores of the experimental group were significantly higher than those of the control group(P＜0.05).In terms of enhancing students'interest in food safety supervision,improving knowledge and skills,cultivating self-directed learning and teamwork abilities,strengthening the close connection between the course and real cases,and providing assistance for future career,the experimental group performed significantly better than the control group(P＜0.05).Moreover,the satisfaction of the experimental group was higher than that of the control group(P＜0.05).Conclusion:BOPPPS teaching model has a remarkable effect in the teaching of Food Safety Supervision and Management course,providing an effective approach for the teaching reform of this course.

Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

Non-suicidal self-injury(NSSI)refers to a mental disorder characterized by deliberate self-harm behaviors without suicidal intent.The pathogenesis of NSSI remains unclear,but may be related to abnormalities in reward circuitry,pain processing,emotion regulation,impulse control and hypothalamic-pituitary-adrenal axis.Task state functional MRI(fMRI)provides valuable insights into the intrinsic connections and neural circuits mechanisms underlying NSSI during various task states or behaviors.Research progresses of task state fMRI in pathogenesis of NSSI were reviewed in this article.

Objective To investigate the articulation acoustic characteristics of children with spastic cerebral palsy and their correlation with articulation intelligibility.Methods A total of 17 children with cerebral palsy and 17 ordinary children aged 6-12 years were included in the study,and the articulation acoustics and articulation intelligi-bility performance of the two types of children were compared by using three kinds of corpus:monophthong,single word and sentence,and the correlation between them was studied.Results The articulation intelligibility of the monophthong,single word and sentence corpus of children with spastic cerebral palsy was lower than that of ordina-ry children(P＜0.01),as follows:monophthong＞single word＞sentence.In the monophthong corpus,only mandibular distance and tongue distance were significantly lower than that of ordinary children(P＜0.05),and only mandibular distance and vowel space area(VSA)were significantly correlated with articulation intelligibility(P＜0.05).In the single word corpus,mandibular distance,tongue distance and VSA were significantly lower than that of ordinary children,while vowel ellipse area(VEA)was significantly higher than that of ordinary children(P＜0.05).All other indexes except VSA and formant centralization ratio(FCR)were significantly correlated with artic-ulation intelligibility(P＜0.05).In the sentence corpus,all the other indexes except mandibular distance were sig-nificantly worse than those of ordinary children(P＜0.05),and all the acoustic indexes were significantly correlated with articulation intelligibility(P＜0.05).Conclusion Children with cerebral palsy have poor articulation acoustic cha-racteristics and articulation intelligibility,and the corpus complexity will affect the degree of correlation between the two.