ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Objective: To investigate the factors influencing the co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia, so as to provide a data foundation and theoretical basis for developing targeted intervention measures. Methods: In September and October 2024, a stratified cluster random sampling method was employed to select 139 102 students from 539 schools across 12 leagues/cities and 103 banners/counties in Inner Mongolia Autonomous Region. Participants who were diagnosed with allergic rhinitis by a doctor at least once within one year and had a body mass index ≥ 28 kg/m 2 were considered to have comorbid conditions. Results: The coprevalence rate of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia was 6.4% (8 931 cases). Lasso-Logistic regression revealed that nonboarding status, higher maternal education, consuming high protein foods ≥1 time daily, occasionally or never eating breakfast, engaging in moderate to vigorous physical activity for ≥60 minutes on fewer than half of holidays, and having been exposed to second hand smoke in person within the past seven days were associated with higher odds ratios for co-prevalence of allergic rhinitis and obesity( OR = 1.23 , 1.22-1.63, 1.20, 1.19, 1.38, 1.35); being female, higher grade level, residence in flag/county/district areas, non only child status, never having consumed a full glass of alcohol, non hypertensive status, and households without pets were associated with lower co-prevalence risks ( OR =0.65, 0.67-0.77, 0.81, 0.87, 0.73, 0.41, 0.68) (all P <0.05). The ROC curve indicated an area under the curve of 0.64 for the predictive model, demonstrating satisfactory discriminatory ability. The calibration curve showed consistency between predicted and actual occurrence probabilities. Conclusions The co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia is closely associated with demographic characteristics, dietary behaviours, and lifestyle habits. Future prevention and control strategies should prioritize these factors to implement targeted interventions.

ObjectiveTo explore the clinical significance of artemin （ARTN） expression in prostate cancer （PCa） tissues and its impact on the malignant behavior of PCa cell lines. MethodsImmunohistochemistry was used to detect the expression of ARTN protein in 40 benign prostate tissues and 91 PCa tissues， and its relationship with the clinical and pathological characteristics of PCa was analyzed. PCa stable cell lines with ARTN knockdown were constructed， and the effects of ARTN on the proliferation， migration， and invasion ability of PCa cells were detected via CCK-8 cell proliferation assay and Transwell assay. Western blot assay was used to detect the effect of ARTN on the expression of epithelial-mesenchymal transition （EMT） related markers E-cadherin， N-cadherin， Vimentin， and Snail family transcription inhibitory factor 1 （Snail-1）. ResultsARTN was highly expressed in PCa and correlated with Gleason score， local lymph node metastasis， and local nerve invasion （P0.05）. Survival analysis showed a statistically significant difference in survival rates between ARTN positive and negative patients （P=0.027）. The results of CCK-8 and Transwell assay showed that the knockdown of ARTN could inhibit the proliferation， migration， and invasion ability of PCa cells （all P0.05）. Western blot results showed that the knockdown of ARTN upregulated the epithelial marker E-cadherin in PCa cells， while the mesenchymal markers N-cadherin， Snail-1， and Vimentin were downregulated. ConclusionARTN is highly expressed in PCa and can promote the proliferation， migration， invasion ability of PCa cells， as well as increasing EMT levels in PCa cells， suggesting it may be a potential target for the diagnosis and treatment of PCa.

Purpose: There is still insufficient evidence for predicting stroke risk in patients with mild carotid atherosclerotic stenosis. This study aimed to explore the association between carotid intraplaque neovascularization (IPN) in mild stenosis and ischemic stroke, using contrast-enhanced ultrasound (CEUS) imaging. Methods: This retrospective observational study included 369 patients from July 2021 to March 2022. These patients were categorized as symptomatic or asymptomatic based on their recent history of ipsilateral ischemic stroke. Initial parameters of carotid plaques, such as IPN grading and contrast enhancement index, were assessed using B-mode ultrasonography and CEUS. The follow-up period lasted 12 months or until a newly-developed ischemic stroke occurred. Logistic regression models and Cox proportional-hazards regression models were employed to explore the associations between ultrasonic parameters and the incidence of recent and future ischemic strokes. Results: In patients with mild stenosis, both increasing age and grade 2 carotid IPN were significant predictors of recent primary ischemic stroke. Furthermore, grade 2 carotid IPN independently predicted future ischemic strokes in both symptomatic and asymptomatic patients. Conclusion This study demonstrated that carotid IPN as detected by CEUS imaging holds potential as a useful non-invasive biomarker for predicting recent and future ischemic strokes in patients with mild carotid stenosis.

Objective To analyze the relationship between humoral immune characteristics and lymph node metastasis status in non-small cell lung cancer(NSCLC)patients,and its predictive value for prognosis.Meth-ods A total of 203 NSCLC patients who were admitted to the hospital from February 2022 to December 2023 were selected.They were divided into two groups,N0+N1 group(n=103)and N2+N3 group(n=100)based on their lymph node metastasis status.Another 100 healthy individuals who underwent physical examinations during the same period were selected as the control group.Clinical data from patients were collected and the propensity score matching method was utilized to match them in a 1∶1 ratio,with 64 cases in each group.A stratified regression model was used to analyze the relationship between humoral immune characteristics and different lymph node metastasis statuses in NSCLC patients.Univariate regression analysis and a multivariate Cox regression model were used to adjust for confounding variables and to explore the independent risk factors of humoral immune characteristics on the prognosis of NSCLC patients.The LOWESS method was used to analyze the two-dimensional curve relationship of continuous variables.The predictive efficacy of humoral im-mune characteristics was evaluated on the prognosis of NSCLC using the area under the receiver operating characteristic and under the curve(AUC).Results Compared with patients in the N0+N1 group,patients in the N2+N3 group had a higher proportion of tumor infiltration depth(T3+T4),high tumor differentiation,and clinical stage(Ⅲ+Ⅳ stage),as well as higher levels of IgA,IgM,IgG,C3,and C4(P＜0.05).Hierarchi-cal regression analysis revealed that IgA,IgM,IgG,C3,and C4 had a significant positive effect on different lymph node metastasis statuses in NSCLC patients(P＜0.05).Univariate and multivariate regression analy-ses revealed that elevated levels of IgA,IgM,IgG,C3 and C4 were independent risk factors for the prognosis of NSCLC(P＜0.05).LOWESS analysis revealed a non-linear relationship between the median overall survival(OS)of NSCLC patients and IgA,IgM,IgG,C3,and C4 levels.The humoral immune characteristics of IgA,IgM,IgG,C3 and C4 showed good predictive performance for the prognosis of NSCLC patients.Conclusion IgA,IgM,IgG,C3 and C4 are independent risk factors for the prognosis of NSCLC patients and demonstrate good predictive performance for the prognosis of NSCLC patients.

Objective:To investigate the impact of Wenyang Ligong Decoction on pregnancy outcomes after transcervical resection of adhesions (TCRA) in patients with intrauterine adhesions (IUA).Methods:A retrospective cohort study was conducted to collect clinical data from 151 patients with IUA who underwent TCRA in the Reproductive Medicine Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between January 2020 and January 2023. Patients were divided into a Traditional Chinese medicine (TCM) group (79 patients) and a control group (72 patients) based on whether they received Wenyang Ligong Decoction after TCRA. The TCM group received estrogen and progesterone sequential therapy post-surgery, combined with Wenyang Ligong Decoction for 2-3 menstrual cycles. The control only received sequential treatment with estrogen and progesterone.Pregnancy outcomes one year after surgery were compared between the two groups. After adjusting for confounding factors using multivariate Cox regression analysis, the effect of Wenyang Ligong Decoction on pregnancy outcomes after TCRA in patients with IUA was observed.Results:The live birth rate [54.43%　(43/79)], the ongoing pregnancy rate [56.96% (45/79)], and the clinical pregnancy rate [52.03% (49/79)] were higher in the TCM group than in the control [26.39% (19/72), P<0.001; 30.56% (22/72), P=0.001;37.50% (27/72), P=0.003], with statistically significant differences. There were no statistically significant differences in early abortion rate and late abortion rate between the TCM group and the control (all P>0.05). According to the stratified analysis by preparation methods, in the natural conception group, the live birth rate [60.78% (31/51)], the ongoing pregnancy rate [62.75% (32/51)], and the clinical pregnancy rate [68.63% (35/51)] in the TCM group were significantly higher than those in control group [21.43% (12/56), P<0.001; 26.79% (15/56), P<0.001; 33.93% (19/56), P<0.001]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the assisted reproductive technology group, there were no statistically significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, early miscarriage rate, and late miscarriage rate between the two groups (all P>0.05). According to the stratified analysis by age, in the <35-year-old patients, the live birth rate [66.00% (33/50)], the ongoing pregnancy rate [70.00% (35/50)], and the clinical pregnancy rate [74.00% (37/50)] in the TCM group were significantly higher than those in control group [41.30% (19/46), P=0.015; 47.83% (22/46), P=0.027; 54.35% (25/46), P=0.044]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05). In the ≥35-year-old patients, the live birth rate [34.48% (10/29)], the ongoing pregnancy rate [34.48% (10/29)], and the clinical pregnancy rate [41.38% (12/29)] in the TCM group were significantly higher than those in control group [0%, P=0.001; 0%, P=0.001; 7.69% (2/26), P=0.004]; there were no statistically significant differences in early miscarriage rate and late miscarriage rate between the two groups (both P>0.05).Univariate Cox regression analysis showed that age, number of previous uterine cavity interventions, IUA score, degree of IUA, and endometrial thickness after TCRA were independent risk factors for live births, and age, IUA score, degree of IUA, intima thickness after TCRA, and treatment group were the influencing factors of persistent pregnancy (all P<0.05). After adjusting for confounding factors, multivariate Cox regression analysis showed that Wenyang Ligong Decoction significantly improved the live birth rate ( HR=3.19, 95% CI: 1.77-8.11, P=0.001) and the rate of continuous pregnancy ( HR=3.66, 95% CI: 1.80-7.48, P<0.001) in patients with IUA. Conclusion:Wenyang Ligong Decoction can significantly improve pregnancy outcomes after TCRA in patients with IUA.

Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Aim To investigate the possible mechanism of the myocardial protective effect of Danzhi Jiangtang capsules(DJC)on db/db mice based on NLRP3 in-flammasome-mediated pyroptosis.Methods The db/db mice were randomly divided into the model group,DJC low,medium,and high dose groups,and the met-formin group,and the db/m mice were taken as the blank group.The administration lasted for eightweeks.At the end of drug administration,blood glucose,blood lipids,cardiac enzymes and inflammatory factors were detected in each group of mice.HE and Masson stai-ning was performed to observe the morphology and fi-brosis of myocardial tissue.TUNEL staining was per-formed to detect apoptosis.RT-qPCR was performed to detect the mRNA expression of ANP,BNP and β-MHC,and Western blot was performed to detect the protein expression of NLRP3,ASC,caspase-1,cleaved-caspase-1,GSDMD and GSDMD-NT in myocardial tis-sue.Results DJC could alleviate myocardial patho-logical damage,reduce collagen deposition and apopto-sis,reduce the levels of blood glucose,blood lipid,myo-cardial enzyme and inflammatory factors in db/db mice.DJC could reduce the mRNA expressions of ANP,BNP and β-MHC,and the protein expressions of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissues.Conclusion DJC attenuates myocardial injury in db/db mice,prob-ably by inhibiting the activation of NLRP3 inflamma-somes,attenuating cardiomyocyte pyroptosis,and amel-iorating the inflammatory state.