OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.

ObjectiveTo construct and validate a clinical prediction model for inflammatory remission outcomes in rheumatoid arthritis （RA） patients with liver and kidney deficiency syndrome treated with Bushen Zhiwang Decoction （补肾治尪汤， BZD） based on metabolomics. MethodsA prospective cohort study was conducted， enrol-ling 60 RA patients with liver and kidney deficiency syndrome. All patients were treated with BZD and conventional-dose oral conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） for 12 months. Clinical data were collected， and the change in disease activity score in 28 joints （DAS28） after treatment compared with baseline （△DAS28） was used as the primary outcome and grouping criterion. Peripheral blood samples were collected before treatment to analyze plasma metabolites. Differential analysis and least absolute shrinkage and selection operator （LASSO） regression were used to preliminarily screen differential metabolites， followed by machine learning algorithms to further identify a core metabolite combination. Based on the expression levels of the core metabolite combination， a novel metabolite index， namely the metabolomics-based inflammatory remission score （Met-IRS）， was calculated using standar-dized metabolite values， and its clinical applicability was evaluated. A clinical prediction model was constructed by integrating clinical characteristics and Met-IRS， and the model performance was assessed. ResultsAmong the 60 patients， those with △DAS28 ≥ 0.27 were assigned to the high inflammatory remission group， while those with △DAS28 ＜ 0.27 were assigned to the low inflammatory remission group， with 30 cases in each group. Compared to the low inflammatory remission group， the high inflammatory remission group showed a higher frequency of methotrexate use and a lower positive rate of rheumatoid factor （RF） （P＜0.05）. Seven core metabolites were identified as the optimal combination， including mangiferic acid， fatty acid-hydroxy fatty acid ester 40∶6， fatty acid-hydroxy fatty acid ester 18∶0， fatty acid-hydroxy fatty acid ester 36∶1， glucosylceramide， lysophosphatidylcholine 22∶5， and pregnanetriol ketone. The calculated Met-IRS comprehensively reflected the characteristics of differential metabolites and demonstrated clinical applicability. Met-IRS was significantly higher in the high inflammatory remission group than in the low inflammatory remission group， and was positively correlated with high inflammatory remission outcomes （P＜0.05）. Based on the variables Met-IRS， methotrexate use， leflunomide use， and RF positivity， a clinical prediction model for inflammatory remission in RA treatment （Cj-RTRM） was constructed. Model performance evaluation demonstrated that the model had good clinical predictive ability， with an area under the receiver operating characteristic curve （AUC） of 0.880， sensitivity 0.967， specificity 0.700 and Youden's index 0.667. ConclusionThe clinical prediction model Cj-RTRM constructed based on the metabolomics-based inflammatory remission score Met-IRS can effectively predict clinical inflammatory remission outcomes in RA patients treated with BZD and accurately identify the advantageous population for this treatment. This model provides guiding evidence for dynamic inflammation monitoring， targeted management， and identification of populations with advantages in traditional Chinese medicine.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

Objective To propose a clinical typing method for lumbar degenerative disease(LDD),including the diagnostic criteria for each type and the corresponding surgical treatment strategies.Methods A total of 245 LDD patients who were admitted to Department of Orthopaedics,The Second Affiliated Hospital of Naval Medical University from Jun.2017 to May 2022 were enrolled and assigned to nerve root type(42 cases),disc herniation type(73 cases),spinal stenosis type(61 cases),spondylolisthesis type(29 cases),and local type(40 cases)according to our diagnostic criteria of clinical typing.Treatment outcomes of various groups were compared and the reliability of the typing method was assessed using consistency test.Results A total of 205 cases received surgical treatment and 40 cases received non-surgical treatment.The surgical approach was modified transforaminal lumbar interbody fusion.The patients were followed up for(20.37±6.13)months.According to Nakai's evaluation criteria,the clinical effect was excellent in 146(59.59％)cases,good in 89(36.33％)cases,fair in 8(3.27％)cases,and poor in 2(0.82％)cases,with an excellent and good rate of 95.92％.There were no significant differences in the treatment effects among different types of LDD(P＞0.05).The results of clinical consistency evaluation confirmed that the typing method had good consistency both within observers and between observers.Conclusion This clinical typing method can help to further understand the pathogenesis of LDD,improve the accuracy of diagnosis and optimize the treatment plan.

This article examines and compares the performance evaluation indicator systems of British and American military hospitals,including their hospital system architecture,indicator frameworks,specific indicators,and evaluation methods.To enhance the comparability of indicators,they were categorized into military attributes,service quality efficiency,economic indicators,and growth and development indicators.Based on the comparative analysis of British and American military hospital performance indicator systems,the following suggestions are proposed for the performance evaluation system of public hospitals in China:(1)increasing the indicator diversity and improving the structure of indicators;(2)optimizing indicator reliability throughout the entire process to enhance the scientific ground of the indicator system;and(3)integrating data assets to facilitate joint application of big data.

Objective To observe the expression levels of base excision repair(BER)pathway-related proteins in small cell lung cancer(SCLC)tissues,and analyze their relationship with the prognosis and tumor immune microenvironment.Methods A retrospective cohort study was conducted on 74 patients with limited-stage SCLC undergoing surgical treatment in our medical center from December 2018 to June 2023.Immunohistochemical staining was performed to analyze the protein expression of BER pathway components,apurinic/apyrimidinic endonuclease 1(APE1),8-oxoguanine DNA glycosylase 1(OGG1),DNA polymerase β(POLβ),X-ray repair cross-complementing protein 1(XRCC1),ATP-dependent DNA ligase I(LIGⅠ),and immune cell infiltration markers of CD3? T cells,CD8? T cells,CD68? macrophages in SCLC tissues.Chi-square test was applied to analyze the relationship of BER protein expression and clinicopathological features;Kaplan-Meier survival curve was plotted to evaluate the impacts of BER protein expression and immune cells on disease-free survival(DFS)and overall survival(OS),multivariate Cox regression analysis was utilized to identify DFS prognostic factors,and Spearman correlation analysis was performed to analyze the correlation of BER-immune cell infiltration.In in vitro experiments,transient transfection was applied in H196 cells to overexpress APE1/POLβ/LIGⅠ,respectively.Thus,the cells were divided into negative control(NC,empty vector)and overexpression(OE,target plasmids)groups.CCK-8 and TUNEL assays were employed to determine the effects of OEAPE1,OEPOLβ and OELIGⅠon cell sensitivity to cisplatin.In in vivo experiments,nude mice bearing xenograft tumors were grouped into WT,E3330(APE1 inhibitor),cisplatin,and cisplatin+E3330 groups to determine the effects of the combination therapy on tumor growth.Results There were no significant correlations of the expression levels of key BER pathway proteins with clinicopathological characteristics,including gender,age,smoking history,tumor location,Ki67 index,or TNM stage(all P>0.05).The patients with low expression of APE1,POLβ,and LIGⅠ had obviously higher DFS rates than those with high expression(P<0.05),and the patients with larger proportion of CD3+T cells also had higher DFS rates than those with smaller proportion(P=0.043).Multivariate Cox regression analysis indicated that tumor TNM stage(HR=2.465)and APE1 expression(HR=2.730)were independent risk factors for the prognosis of SCLC patients(P<0.05).Spearman correlation analysis demonstrated a positive correlation between APE1 and CD8+T cell proportion in the SCLC patients(r=0.27,P<0.05).In vitro experiments showed that the overexpression(OE)cells(OEAPE1 and OELIGⅠ)exhibited reduced sensitivity to cisplatin than the NC group(P<0.05).Animal experiments indicated that cisplatin+E3330 significant inhibited xenograft tumor growth,indicating enhanced therapeutic efficacy(P<0.01).Conclusion High expression of APE1,POLβ,and LIGⅠ in the BER pathway indicates poor prognosis and low DFS rate in SCLC patients.High expression of APE1 is positively correlated with CD8+T cells,and can be used as an auxiliary marker for SCLC immunotherapy.

Objective:To explore the relationship between maternal rejection and internet addiction in college students, as well as the chain mediating role of rejection sensitivity and adaptability.Methods:From March to May 2024, a total of 1 119 college students were surveyed using the short-form Egna Minnen av Barndoms Uppforstran for Chinese(s-EMBU-C), internet addiction test(IAT), rejection sensitivity questionnaire(RSQ), and the China college student adjustment scale(CCSAS).SPSS 26.0 statistical software was used for independent sample t-test, one-way ANOVA, Pearson product moment correlation, and multiple linear regression analysis, and PROCESS 4.0 macro program was used for chain mediation analysis. Results:(1)Maternal rejection (11.19±2.97) was positively correlated with internet addiction (44.89±9.74)( r=0.60, P<0.01) and rejection sensitivity (102.93±55.63)( r=0.63, P<0.01), while negatively correlated with adaptability (200.19±14.18)( r=-0.56, P<0.01) among college students. Rejection sensitivity was positively correlated with internet addiction ( r=0.75, P<0.01) and negatively correlated with adaptability ( r=-0.76, P<0.01). Adaptability was negatively correlated with internet addiction ( r=-0.68, P<0.01). (2)Maternal rejection had a significant direct effect on internet addiction among college students (effect value=0.193, 95% CI=0.145-0.241), accounting for 32.06%(0.193/0.602) of the total effect. Rejection sensitivity mediated the relationship between maternal rejection and internet addiction (effect value=0.290, 95% CI=0.232-0.357), accounting for 48.17%(0.290/0.602) of the total effect. Adaptability also mediated this relationship (effect value=0.028, 95% CI=0.009-0.053), accounting for 4.65%(0.028/0.602) of the total effect. Additionally, there was a chain mediation effect of rejection sensitivity and adaptability on the relationship between maternal rejection and internet addiction (effect value=0.091, 95% CI=0.052-0.130), accounting for 15.12%(0.091/0.602) of the total effect. Conclusion:Maternal rejection can directly influence internet addiction in college students, and it can also indirectly influence internet addiction through the independent mediating effects of rejection sensitivity and adaptability, as well as through the chain mediating effects of both rejection sensitivity and adaptability.

Objective:To explore the effects of perceived stress on ego depletion of college students, as well as the mediating role of emotional eating and the moderating role of peer relationship.Methods:A cross-sectional survey of 1 088 college students was conducted using the perceived stress scale, the Dutch eating behavior questionnaire, the self-control resource depletion scale, and the peer relationship measurement from December 2023 to April 2024.PROCESS Macro program in SPSS 25.0 software was used to test the mediating effect of emotional eating and the moderating effect of peer relationship.Results:(1)The score of perceived stress, emotional eating, peer relationship and ego depletion were 39.26±8.35, 39.19±12.15, 2.00(1.00), and 18.19±7.15, respectively.(2)Perceived stress was positively correlated with emotional eating, ego depletion, and peer relationship( r=0.36, 0.61, 0.25, all P<0.01). Emotional eating was positively correlated with ego depletion and peer relationship( r=0.40, 0.19, both P<0.01). And ego depletion was positively correlated with peer relationship( r=0.23, P<0.01).(3)Emotional eating played a partial mediating role in the effect of perceived stress on ego depletion( β=0.077, 95% CI=0.053-0.104), and the mediating effect accounted for 12.38%(0.077/0.622) of the total effect.(4)Peer relationship played a moderating role between perceived stress and emotional eating. Under low peer relationship, perceived stress had a significant positive predictive effect on emotional eating( βsimple=0.46, P<0.01), and under high peer relationship, the predictive effect of perceived stress on emotional eating was significantly weaker( βsimple=0.26, P<0.01). Conclusions:Perceived stress not only directly affects ego depletion, but also indirectly affects ego depletion through emotional eating in college students.High levels of peer relationship can weaken the impact of perceived stress and high emotional eating on ego depletion.

Objective:To evaluate the diagnostic value of coronary angiography-derived fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) for identifying coronary functional abnormalities.Methods:This diagnostic study enrolled patients with clinically suspected or diagnosed coronary artery disease who underwent coronary angiography at Beijing Anzhen Hospital, TEDA International Cardiovascular Hospital, and Qilu Hospital of Shandong University between December 2021 and June 2022. All enrolled patients successfully underwent invasive wire-based FFR and IMR measurements during angiography. In a core laboratory, FFR and IMR for the target vessels were measured using artificial intelligence technology based on coronary angiographic images. Spearman correlation analysis was used to evaluate the correlation between angiography-derived FFR and wire-based FFR, and between angiography-derived IMR and wire-based IMR. Coronary hemodynamic abnormality was defined as FFR≤0.80; the diagnostic performance of angiography-derived FFR for identifying this abnormality was evaluated. Microcirculatory dysfunction was defined as IMR≥25; the diagnostic performance of angiography-derived IMR for identifying microcirculatory dysfunction was evaluated.Results:A total of 181 patients, aged (60.6±8.8) years, with 62 (34.3%) females, and 181 target vessels were included in the final analysis. Angiography-derived FFR showed a significant positive correlation with wire-based FFR ( r=0.78, P<0.001). For identifying coronary hemodynamic abnormality, angiography-derived FFR showed an accuracy of 89.0%, sensitivity of 88.8%, specificity of 89.1%, positive predictive value (PPV) of 88.8%, negative predictive value (NPV) of 89.1%, and an area under the receiver operating characteristic curve ( AUC) of 0.88. Angiography-derived IMR showed a significant positive correlation with wire-based IMR ( r=0.93, P<0.001). For identifying microcirculatory dysfunction, angiography-derived IMR demonstrated an accuracy of 89.5%, sensitivity of 86.8%, specificity of 90.2%, PPV of 70.2%, NPV of 96.3%, and an AUC of 0.95. Conclusion:Angiography-derived FFR and IMR exhibit strong correlations with their invasive wire-based counterparts and demonstrate high diagnostic value for assessing coronary hemodynamics and coronary microcirculatory function.