ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties， this paper systematically contrasted the quality differences between wild Polygalae Radix（WPR） and cultivated Polygalae Radix（CPR） from the aspects of character， microscope and chemical composition by modern scientific and technological means， providing a basis for high-quality production and quality control. MethodsCPR and local WPR in Yulin city， Shaanxi province from 1 to 6 years were collected， and a systematic comparative analysis was conducted using traditional pharmacognosy research methods combined with modern multi-omics analysis techniques， including character traits（length， weight， diameter）， cross-sectional microscopic features（proportions of cork， phloem， xylem， etc）， cell wall component content（hemicellulose， cellulose， lignin）， extracts content（water-soluble extract and alcohol-soluble extract）， carbohydrate content（starch， water-soluble polysaccharides）， contents of total flavonoids， total saponins and specific marker compounds（3，6′-disinapoyl sucrose， polygalaxanthone Ⅲ， tenuifoliside A， tenuifoliside C， sibiricose A₅ and A₆） and other indexes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to conduct comparative analysis of secondary metabolites in WPR and CPR， and multivariate statistical analysis such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to screen the key differential components of them. ResultsIn terms of appearance， there were significant differences between WPR and CPR. The characteristics of WPR conformed to the "thick wrinkles on the epidermis" recorded in ancient books， featuring a wrinkled surface and grayish-brown appearance. However， CPR had a finer texture and a yellowish white appearance， with weight， length， and diameter increasing with longer cultivation periods. In terms of microscopy， WPR exhibited a thick cork layer with fissures in the phloem， whereas CPR had a thinner cork layer with uniformly arranged cork cells. Younger PR specimens showed numerous phloem fissures in cross-sections， while older specimens display progressively denser arrangements of phloem parenchyma cells. In terms of the contents of various major components， the contents of water-soluble extract， starch and total saponins in WPR were inversely proportional to the root diameter， while the contents of water-soluble extract， water-soluble polysaccharides and total saponins in CPR decreased with the increase of planting years. The content of xanthones in WPR was significantly higher than that of CPR， while the contents of other major components showed no significant change pattern. Among the six indicator components， the average content of sibiricose A₅ in WPR was significantly higher than that of CPR， followed by slightly higher content of tenuifoliside A. In CPR， the relative content of 3，6′-disinapoyl sucrose and tenuifoliside A was the highest. The former showed an increase in volatility with increasing cultivation years， while the latter showed a decrease in volatility. The results of differential compound analysis based on UPLC-Q-TOF-MS showed that there were significant differences in metabolites between WPR and CPR samples. Among them， the seven compounds with the largest differences among WPR samples of different thicknesses were polygalasaponins， and for CPR with different planting years， the main differential compounds were oligosaccharide esters. ConclusionThere are differences between WPR and CPR in character， microscopic structure and chemical composition， and some components are inversely proportional with the increase of diameter and cultivation duration due to the distribution characteristics. However， the longer the cultivation years of PR， the closer it is to the "thick wrinkles on the epidermis" of WPR， which has been respected by generations. It is suggested that this traditional character combined with modern component contents should be used as the index of artificial cultivation and quality control of PR.

Objective: To assess the causal association between specific oral microbiota and the risk of oral leukoplakia (OLK) using a Mendelian randomization (MR) approach, and to elucidate the potential mediating role of immune cells. Methods: Summary statistics from genome-wide association studies (GWAS) of the oral microbiome, GWAS data for immune cell phenotypes, and GWAS summary statistics for OLK from FinnGen were used. The inverse variance weighted (IVW) method was adopted as the primary approach, and it was supplemented by MR Egger regression, simple mode, weighted median, and weighted mode methods for additional analyses, to investigate the causal relationship between 3 117 types of tongue coating and salivary microbiota, as well as 731 immune cell traits, and OLK. Furthermore, a two-step MR approach was applied to explore the potential mediating role of immune cells in the association between oral microbiota and OLK. Results: IVW analysis revealed causal associations between 15 oral microbial genera and OLK. Among these, Streptococcus, Neisseria, and Catonella were associated with a reduced risk of OLK, with Fusobacterium showing the most significant protective effect (OR = 0.41, P = 0.023). In contrast, genera, including Microbacterium, Campylobacter, and Haemophilus_A, were linked to an increased risk of OLK, with Lancefieldella exhibiting the strongest risk effect (OR = 2.66, P = 0.006). Eleven immune cell phenotypes with potential causal associations with OLK were identified, including four protective and seven risk-increasing factors. Mediation analysis further identified four key mediating pathways: pathogenic genera, particularly Campylobacter_A and Lancefieldella, may promote the development and progression of OLK by upregulating highly activated pro-inflammatory immune subsets such as activated monocytes, B cells, and myeloid cells. Conversely, the potentially protective genus Catonella appeared to exert inhibitory effects on OLK by significantly downregulating dendritic cell subsets. Conclusion This study is the first to reveal, at the genetic level, causal pathways through which specific oral microbial genera influence the risk of OLK by mediating immune cell responses. These findings provide novel insights into the immunopathological mechanisms underlying OLK and offer potential targets for intervention strategies aimed at modulating specific microbial genera or immune cell subsets.

OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions， as well as to review the payment methods of drugs （including in-hospital and external drug dispensing）. METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally， an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 （before the system upgrade） and May to August 2025 （after the system upgrade）. RESULTS After the upgrade of the pre-prescription review system， the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval （CI）＝0.3%-6.7%， P ＝0.037 ] ； the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level （95%CI＝31.6%-88.5%， P ＝0.026）， and the average monthly sequential decrease was 29.5% （95%CI＝12.2%-43.4%， P ＝0.012）. Moreover， the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade， a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs， and strengthens the supervision of off-label drug use， achieving dual guarantees of clinical rationality and medical insurance compliance.

OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

The onset and progression of chronic heart failure （CHF） are closely associated with myocardial energy metabolism disorders， and this pathological process significantly affects patient prognosis. Traditional Chinese medicine （TCM）， grounded in time-based medical theories such as the correspondence between humans and nature and the theory of circadian flow of meridians （Ziwu Liuzhu）， exhibits intrinsic consistency with modern circadian rhythm theory， providing a unique theoretical framework for understanding and intervening in CHF from a temporal perspective. This article systematically explores the impact of circadian rhythms on energy metabolism and the potential mechanisms by which TCM active ingredients intervene in CHF through a review of relevant literature. It is found that various TCM active ingredients， including flavonoids （such as nobiletin）， alkaloids （such as berberine）， and polyphenols （such as resveratrol）， can improve mitochondrial function， promote fatty acid oxidation， enhance glucose uptake and utilization efficiency， maintain metabolic balance， and alleviate oxidative stress and inflammatory responses in myocardial cells by regulating the expression and rhythms of core circadian clock genes such as CLOCK， BMAL1， PER， and CRY. These actions thereby correct energy metabolism disorders and improve cardiac function. Further exploration of the interaction mechanisms between these components and the circadian rhythms holds promise for providing novel theoretical foundations and potential intervention strategies for the prevention and treatment of CHF.

Objective: To explore the relative importance of different food attributes and levels in food decision making of school aged children, and to understand their meal preferences, so as to provide the evidence for formulating precise intervention strategies for dietary behaviours of school aged children. Methods: From May to June 2024, a total of 854 children aged 11 to 15 years old were selected from 2 middle schools (each school in urban and rural areas) in both Hubei Province and Anhui Province by stratified cluster random sampling method to conduct a D-optimal discrete choice experiment. The mixed Logit model was used to analyze children s preference for meal attributes and different levels, and to calculate the relative importance (RI) of attributes and willingness to pay (WTP) in meal choices. Results: The included five food attributes had statistical significance on meal choice of school aged children ( P <0.05). The relative importance of food attributes affecting the meal choices of school aged children in descending order were dining mode ( RI =31.26%), food varieties ( RI =30.56%), cooking method( RI =23.84%), taste( RI =8.06%) and price ( RI =6.27%). Among them, school aged children preferred home cooked meals ( β =0.74) (WTP=86.3 yuan),varied foods(grain/tubers+vegetables+fish, meat, eggs and beans) ( β =0.61) (WTP=71.9 yuan), fried/roasted cooking ( β =0.51) and spicy taste ( β =0.33).Price was negatively correlated with meal choices( β =-0.01) ( P <0.05). Based on residential area and body mass index (BMI), the stratified analysis showed that dining mode was highest in the relative importance for rural children with overweight and obese children ( RI =31.28%,34.17%), both of whom preferred home cooked meals ( β =0.76, 0.91), and meals containing fish, meat, eggs and beans with grain/tubers or grain/tubers and vegetables in terms of food choice (area: β =0.53, 0.53 ; BMI: β =0.55, 0.56) ( P <0.05). Conclusions School aged children have different preferences for different attributes of meals. The quality of school meals should be improved,the cost of buying healthy meals should be reduced,targeted family health education should be carried out,and healthy cooking methods should be advocated.

Exercise fatigue is a complex physiological and psychological phenomenon that includes peripheral fatigue in the muscles and central fatigue in the brain. Peripheral fatigue refers to the loss of force caused at the distal end of the neuromuscular junction, whereas central fatigue involves decreased motor output from the primary motor cortex, which is associated with modulations at anatomical sites proximal to nerves that innervate skeletal muscle. The central regulatory failure reflects a progressive decline in the central nervous system’s capacity to recruit motor units during sustained physical activity. Emerging evidence highlights the critical involvement of central neurochemical regulation in fatigue development, particularly through neurotransmitter-mediated modulation. Alterations in neurotransmitter release and receptor activity could influence excitatory and inhibitory signal pathways, thus modulating the perception of fatigue and exercise performance. Increased serotonin (5-HT) could increase perception of effort and lethargy, reduce motor drive to continue exercising, and contribute to exercise fatigue. Decreased dopamine (DA) and noradrenaline (NE) neurotransmission can negatively impact arousal, mood, motivation, and reward mechanisms and impair exercise performance. Furthermore, the serotonergic and dopaminergic systems interact with each other; a low 5-HT/DA ratio enhances motor motivation and improves performance, and a high 5-HT/DA ratio heightens fatigue perception and leads to decreased performance. The expression and activity of neurotransmitter receptors would be changed during prolonged exercise to fatigue, affecting the transmission of nerve signals. Prolonged high-intensity exercise causes excess 5-HT to overflow from the synaptic cleft to the axonal initial segment and activates the 5-HT1A receptor, thereby inhibiting the action potential of motor neurons and affecting the recruitment of motor units. During exercise to fatigue, the DA secretion is decreased, which blocks the binding of DA to D1 receptor in the caudate putamen and inhibits the activation of the direct pathway of the basal ganglia to suppress movement, meanwhile the binding of DA to D2 receptor is restrained in the caudate putamen, which activates the indirect pathway of the basal ganglia to influence motivation. Furthermore, other neurotransmitters and their receptors, such as adenosine (ADO), glutamic acid (Glu), and γ‑aminobutyric acid (GABA) also play important roles in regulating neurotransmitter balance and fatigue. The occurrence of central fatigue is not the result of the action of a single neurotransmitter system, but a comprehensive manifestation of the interaction between multiple neurotransmitters. This review explores the important role of neurotransmitters and their receptors in central motor fatigue, reveals the dynamic changes of different neurotransmitters such as 5-HT, DA, NE, and ADO during exercise, and summarizes the mechanisms by which these neurotransmitters and their receptors regulate fatigue perception and exercise performance through complex interactions. Besides, this study presents pharmacological evidence that drugs such as agonists, antagonists, and reuptake inhibitors could affect exercise performance by regulating the metabolic changes of neurotransmitters. Recently, emerging interventions such as dietary bioactive components intake and transcranial electrical stimulation may provide new ideas and strategies for the prevention and alleviation of exercise fatigue by regulating neurotransmitter levels and receptor activity. Overall, this work offers new theoretical insights into the understanding of exercise central fatigue, and future research should further investigate the relationship between neurotransmitters and their receptors and exercise fatigue.

ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region （3’UTR） of slit guidance ligand 1 （Slit1） （Slit1-3’UTR） on the fibrotic phenotypes of cardiac fibroblasts （CFs） and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs （mCFs）. The expression of fibrosis-related genes in mCFs， such as collagen type 1 alpha1（COL1A1）， collagen type 3 alpha3 （COL3A1） and alpha smooth muscle actin （α-SMA） were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ （Ang Ⅱ） was used to treat mCFs， and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt， miR-34a-5p mimic was transfected into mCFs， followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt， and the levels of miR-34a-5p and its target gene SIRT1（si-SIRT1） in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes， proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs， while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes， and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.

Background The decline of physical activity in the elderly due to aging may increase the risk of sarcopenia. Currently, there is a lack of evidence from large natural populations on the relationship between PA and sarcopenia. Objective To explore the relationship between PA and sarcopenia in the elderly aged 60 years and above in 10 provinces (autonomous regions) of China. Methods Data were retrieved from the 2022—2023 round of the China Development and Nutrition Health Impact Cohort. Personal basic information and PA data were collected by questionnaire survey. Skeletal muscle mass was measured by bio-electrical impedance analysis, muscle strength was measured using a grip dynamometer, and physical performance was reflected by 6-meter walk speed. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to diagnose sarcopenia. Light physical activity (LPA) duration, moderate-to-vigorous physical activity (MVPA) duration, and total physical activity volume were calculated. A total of 3326 residents aged ≥60 years with complete data were selected as the survey participants. Multiple logistic regression models and restricted cubic splines (RCS) were used to assess the association between PA duration/volume and sarcopenia. Results In 10 provinces (autonomous regions) of China, the prevalence of sarcopenia in the elderly aged 60 years and above was 5.5% (95%CI: 4.7%, 6.2%). The logistic regression analysis showed that compared with the elderly reporting 0-7.0 h·week⁻¹ in LPA duration, the risk of sarcopenia in the elderly with LPA duration of >14.0-21.0 h·week⁻¹ was reduced by 51% (OR=0.49, 95%CI: 0.26, 0.96). Compared with the elderly with total physical activity ≥15.0 metabolic equivalent of task (MET)-h·week⁻¹, those with <7.5 MET-h·week⁻¹ had a 2.24-fold increased risk of sarcopenia (OR=2.24, 95%CI: 1.17, 4.29). The RCS results found that LPA duration and total physical activity volume each showed a nonlinear dose-response relationship with the risk of sarcopenia (P_overall<0.05, P_non-linear<0.05). Compared with the elderly with an LPA duration of 0 h· week⁻¹, the risk of sarcopenia in the elderly with an LPA duration of 12.6 h· week⁻¹ was the lowest (OR=0.42, 95%CI: 0.21, 0.83). Compared with the elderly with a total physical activity volume of 15.0 MET-h· week⁻¹, the elderly with a total physical activity volume of 46.0 MET-h· week⁻¹ had the lowest risk of sarcopenia (OR=0.57, 95%CI: 0.38, 0.84). There was no statistically significant association between weekly MVPA duration and the risk of sarcopenia (P>0.05). Conclusion Increasing weekly LPA duration and total physical activity volume would help to reduce the risk of sarcopenia.