ObjectiveTo investigate the effects of the combination of components from Tripterygii Radix et Rhizoma and Chuanxiong Rhizoma on rheumatoid arthritis fibroblast-like synoviocytes （RA-FLSs） and the underlying mechanism. MethodsRA-FLSs were grouped as follows： blank control， positive control （methotrexate）， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma. The cell-counting kit-8 （CCK-8） assay was employed to the cell proliferation， invasion， and apoptosis. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， reactive oxygen species （ROS）， and malondiadehyde （MDA） in cells were measured. Western blot was employed to determine the protein levels of nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB） p65， phosphorylated inhibitory subunit of NF-κBα （p-IκBα）， cysteinyl aspartate-specific protease-3 （Caspase-3）， and B-cell lymphoma 2 （Bcl-2）. Real-time PCR was employed to determine the mRNA levels of Nrf2， HO-1， and NF-κB p65. ResultsThe cells in the groups of positive control， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma were treated with 2.50 mg·L^-1 methotrexate， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol， 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol + 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， respectively. Compared with the blank control group， drug administration reduced the proliferation and invasion and increased the apoptosis of cells （P<0.01）， lowered the levels of TNF-α， IL-6， ROS， and MDA （P<0.01）， up-regulated the mRNA and protein levels of Caspase-3， Nrf2， and HO-1 （P<0.01）， and down-regulated the mRNA and protein levels of Bcl-2， NF-κB p65， and p-IκBα （P<0.01）. Compared with the Tripterygii Radix et Rhizoma components group， the combination of components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma inhibited the proliferation and invasion （P<0.05） and promoted the apoptosis of RA-FLSs， up-regulated the mRNA levels of Nrf2 and HO-1 and protein levels of Nrf2 and Caspase-3 （P<0.05）， and down-regulated the protein levels of NF-κB p65 and p-IκBα （P<0.05）. ConclusionThe combination of components from Chuanxiong Rhizoma and Tripterygii Radix et Rhizoma can inhibit the proliferation and invasion and promote the apoptosis of RA-FLSs and alleviate oxidative stress and inflammation by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 pathway， and regulating the expression of Bcl-2/Caspase-3.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective To investigate the effects of Aurora kinase A(AURKA)on the tumor microenvironment of colorectal cancer(CRC)and to predict the active compounds in Chinese herbs that can target AURKA.Methods Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas(TCGA)database,the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.Results The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues(P＜0.05),and CRC patients with high AURKA expression had shorter overall survival.Compared with the AURKA low-expression group,the abundance of macrophages,monocytes,and effector memory CD4+and CD8+T cells was significantly downregulated in the AURKA high-expression group(P＜0.05).In addition,the cytotoxicity of T cells was significantly reduced(P＜0.05).Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells(MDSCs)and the expression levels of their chemokines CXCL2 and CXCL5(P＜0.05).Genes that were differentially expressed between the AURKA high-and low-expression groups were mainly enriched in monocyte migration,chemokine-induced cellular responses,and other related processes.Chinese herbal compounds,including hesperidin,aristololactam A Ⅱ a,anacardic acid,coumestrol,and 17β-estradiol,all showed binding energies to AURKA lower than-1.2 kcal/mol,indicating a certain level of binding stability.Among these Chinese herbal compounds,17β-estradiol exhibited the best binding stability to AURKA-3UOL.Conclusion The high expression of AURKA in CRC tissues suggests a poor clinical prognosis.AURKA can promote the development of a suppressive immune microenvironment in CRC,and 17β-estradiol,an active compound from Chinese herbs,is a potential therapeutic agent targeting AURKA.

Objective To explore medical institution-led exercise training interventions,prelimina-ry preventive measures,and comprehensive health service strategies for elderly adults.Methods Sixty elderly adults from communities under the jurisdiction of primary hospitals who voluntarily participated in the training and met the inclusion criteria were divided into 75 to 79 years old group and 80 to 84 years old group.Elastic bands exercise were selected as the method for physical training for elderly community members.A total of three sets(9 items)of exercise,including upper and lower limb mus-cle strength exercises and balance as well as coordination training,were designed.The training period lasted for 12 weeks,with each session lasting 1 hour,three times a week.The medical team partici-pated in training supervision and follow-up evaluations throughout the process,dynamically adjusting the training intensity based on individual needs.Results Comprehensive safety and support meas-ures significantly improved training participation and completion rates.No sports injuries or adverse events occurred throughout the process,and all participants completed the training plan.After train-ing,statistically significant differences were observed in grip strength,five-times sit-to-stand test duration,Berg Balance Scale(BBS)scores,and Timed Up and Go(TUG)test results(P＜0.05),indicating effective physical fitness improvement.Conclusion Elastic band exercises are a suitable mode for physical improvement training among elderly adults,significantly enhancing muscle strength in the limbs and trunk and improving balance function.The positive communication and in-teraction in group activities significantly boost elderly adults'confidence in healthy living,leading to notable improvements in their mental state.

Objective To investigate the therapeutic effects and mechanisms of emodin(EMO)on dextran sulfate(DSS)-induced ulcerative colitis(UC)in mice.Methods DSS induced UC mouse model,detection of body weight,colon length and histopathological changes.Enzyme-linked immunosorbent assay(ELISA)was used to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),and myeloperoxidase(MPO)levels.Western blot analysis examined the expression of Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor κB(NF-κB)signaling pathway-related proteins.Flow cytometry assessed the ratio of helper T cells 17(Th17)to regulatory T cells(Treg).Additionally,16S rDNA sequencing was employed to evaluate gut microbiota composition.Results Compared with the normal group,DSS-treated mice exhibited significant weight loss,shortened colon length,and marked histological damage(P<0.001).EMO intervention,particularly at high doses,demonstrated dose-dependent improvements in body weight and colon injury(P<0.05).ELISA analysis showed EMO reduced TNF-α,IL-1β,and IL-6 levels while increasing IL-10(P<0.05).Western blot results indicated EMO inhibited abnormal activation of the TLR4/MyD88/NF-κB pathway and restored IκB.Conclusion EMO effectively mitigates DSS-induced ulcerative colitis(UC)inflammation and intestinal damage by regulating the TLR4/MyD88/NF-κB pathway,restoring Th17/Treg balance,and maintaining microbial homeostasis,providing theoretical support for its potential as a UC therapeutic agent.

Objective A feasible and stable mouse model of thoracic aortic dissection(TAD)combined with acute lung injury(ALI)was established using β-aminopropionitrile monofumarate(BAPN)1 g/(kg·d)administered in drinking water.The mouse model of TAD combined with acute lung injury(ALI)was established to provide a rational animal model to study TAD combined with ALI.Methods Forty-five SPF-grade 3-week-old C57BL/6J male mice were selected and randomly allocated to a CON group(normal dietary water;15 mice)or BAPN group(administration in sterile water at 1 g/(kg·d);30 mice)for 4 weeks.During the experimental period,the general condition and modeling rate of mice were observed.TAD model mice were validated,and the BAPN group was divided into TAD and non-TAD groups by measuring the maximum diameter of the thoracic aorta and HE staining of aortic tissues.HE pathological staining,the wet/dry weight(W/D)ratio,total protein level in bronchioalveolar lavage fluid(BALF),and interleukin(IL)-1 β,IL-6,and tumor necrosis factor-α(TNF-α)in BALF)were used to validate the TAD combined ALI model in mice.Results BAPN treatment significantly delayed the increase in body mass and water intake of mice.Compared with CON and non-TAD groups,the maximum diameter of the thoracic aorta of mice in the TAD group was significantly thickened(P＜0.05).HE staining of the aorta showed significant thickening of the middle aortic layer,and the structure of the aortic wall was damaged and disordered.HE staining of lung tissues showed significant interstitial edema and inflammatory exudation accompanied by enlargement of alveolar lumen,alveolar wall epithelial exfoliation and hyaline membrane formation,and a significant increase in the pathological scores of lung injury(P＜0.05).Total protein levels and expression of IL-1β,IL-6,and TNF-α in lung tissue,W/D ratio,and BALF were also significantly increased(P＜0.05),whereas no significant difference was observed in the above indexes between the other two groups.Conclusions A mouse model of thoracic aortic dissection combined with acute lung injury can be established by BAPN administration in drinking water.

Objective:To explore the prognostic factors associated with clear cell adenocarcinoma (CCAC) of the uterine cervix based on data in the Surveillance, Epidemiology and End Results (SEER) database.Methods:Clinical data were collected from 431 patients with confirmed CCAC in the SEER database from 1976 to 2017. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison between subgroups. Cox proportional hazards model was used to analyze the influencing factors of overall survival (OS).Results:The median age [ M ( Q1, Q3)] of 431 patients was 54 years old (40 years old, 71 years old); there were 333 cases (77.3%) of whit. The median OS time of 431 patients was 93 months (95% CI: 47-148 months), and the 1-, 2-, and 5-year OS rates were 80.1%, 65.8% and 54.2%, respectively. The median OS time was not reached in patients with American Joint Committee on Cancer (AJCC) stage Ⅰ, 83 months (95% CI: 21-144 months) for stage Ⅱ, 32 months (95% CI: 16-47 months) for stage Ⅲ, and 9 months (95% CI: 5-13 months) for stage Ⅳ ( P < 0.001). Median OS time was not reached in patients with SEER stage of localized lesions, 46 months (95% CI: 8-83 months) for regional lesions stage, and 9 months (95% CI: 5-12 months) for distant metastases stage ( P < 0.001). Of the patients with clear AJCC staging and some with unspecified AJCC staging, 118 received surgical treatment alone and 119 received postoperative radiotherapy, the median OS time of the two groups was 443 months (95% CI: 162-723 months) and 102 months (95% CI: 75-129 months), and the difference in OS between the two groups was statistically significant ( P < 0.001). Among the patients with AJCC stage Ⅰ, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 82.5% and 78.5%, the stage Ⅱ were 80.0% and 52.3%, and the stage Ⅲ were 27.8% and 63.3%, respectively; the differences in OS between different stages were not statistically significant (all P>0.05). Among the patients with SEER localized lesions stage, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 88.9% and 73.1%, and the difference was statistically significant ( P = 0.012); the regional lesions stage were 45.5% and 60.0%, and the difference was not statistically significant ( P = 0.568). The results of multivariate Cox regression analysis showed that AJCC staging (stage Ⅰ vs. stage Ⅳ, HR = 0.281, 95% CI: 0.178-0.543, P < 0.001; stage Ⅱ vs. stage Ⅳ, HR = 0.347, 95% CI: 0.113-0.439, P < 0.001; stage Ⅲ vs. stage Ⅳ, HR = 0.399, 95% CI: 0.030-0.145, P < 0.001), SEER staging (localized lesions stage vs. distant metastases stage, HR = 0.104, 95% CI: 0.059-0.182, P < 0.001; regional lesions stage vs. distant metastases stage, HR = 0.301, 95% CI: 0.195-0.463, P < 0.001) and whether or not receive surgery (yes vs. no, HR = 0.359, 95% CI: 0.241-0.535, P < 0.001) were independent influencing factors of OS in CCAC patients. Conclusions:AJCC staging, SEER staging and surgery are independent influence factors for OS in patients with CCAC, and postoperative radiotherapy may not provide more survival benefit.

Background Sleep is a crucial physiological activity for the human body, and research has shown that air pollution can affect sleep quality. However, the association between polycyclic aromatic hydrocarbons (PAHs) exposure, neurotoxic compounds in air pollutants, and sleep quality remains uncertain. Objective To evaluate the association of PAHs exposure with sleep quality, and to provide evidence for improving sleep quality. Methods This study used a cross-sectional design. We selected 632 workers from a coking plant of a large state-owned enterprise as the exposure group, and 477 workers from the energy and power plant of the same enterprise as the control group. All workers worked in three shifts. A questionnaire survey was conducted to collect basic information including gender, years of service, age, educational level, smoking, alcohol consumption, consumption of fried foods, cooking frequency, types of cooking fuels. Worker's post-shift morning midstream urine was sampled to determine the concentrations of eight PAHs metabolites (OH-PAHs) using gas chromatography-tandem mass spectrometry (GC-MS). Worker's sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). A higher PSQI score indicated a lower sleep quality. Associations of urinary OH-PAHs levels with sleep quality in the workers were analyzed using linear regression, Bayesian kernel-machine regression (BKMR), and quantile g-computation. Results The median (P₂₅, P₇₅) concentration of total OH-PAHs in the exposure group [88.84 (46.27, 151.96) μg·L⁻¹] was higher than that in the control group [54.33 (24.86, 97.97) μg·L⁻¹]. Additionally, the PSQI score (\begin{document}$ \overline{x}\pm {s} $\end{document}) in the exposure group (5.16±3.84) was higher than that in the control group (4.60±3.17). The multiple linear regression revealed that an increase in the sum of the concentrations of eight OH-PAHs after natural logarithmic transformation (lnΣ₈OH-PAHs) was associated with an increase of 0.3646 (95%CI: 0.1337, 0.5955) in PSQI score, and an increase in lnΣlow-ring OH-PAHs was associated with an increase of 0.2954 (95%CI: 0.0941, 0.4967) in PSQI score. The BKMR analysis demonstrated that PSQI score was gradually increased as the increasing of lnΣ₈OH-PAHs concentration. The quantile g-computation analysis indicated that a quantile increase in lnΣ₈OH-PAHs concentration was associated with an increase of 0.4062% (95%CI: 0.1176%, 0.6949%) in PSQI score. Conclusion Compared to the controls, the coking workers show a higher concentration of urinary OH-PAHs and report worse sleep quality. The concentration of OH-PAHs is significantly negatively associated with sleep quality.

Objective To analyze the prognostic value of serum microRNA(miRNA)-21-5p and miRNA-5189-5p expression levels in elderly patients with prostate cancer after laparoscopic radical prostatectomy(LRP).Methods A total of 213 elderly prostate cancer patients treated with LRP from January 2014 to Sep-tember 2018 in the First Affiliated Hospital of Hainan Medical College were retrospectively selected as the study objects.According to the 5-year follow-up outcome,the patients were divided into good prognosis group(87 cases)and poor prognosis group(126 cases).The preoperative clinical baseline data and the expression levels of serum miRNA-21-5p and miRNA-5189-5p were collected.Logistic regression analysis was used to screen the factors affecting the prognosis of patients.The prognostic prediction model was constructed with independent risk factors,and the predictive value was analyzed by drawing receiver operating characteristic(ROC)curve.Results Multivariate Logistic regression analysis showed that serum prostate specific antigen(PSA)level,positive incisal margin,and expression levels of miRNA-21-5p and miRNA-5189-5p were inde-pendent risk factors for the prognosis of elderly prostate cancer patients receiving LRP(P＜0.05).The com-bined prediction model was established based on independent risk factors,and the area under the curve of each factor alone predicting prognosis of elderly prostate cancer patients receiving LRP was less than that of four combined prediction(P＜0.05).Conclusion The expression levels of serum miRNA-21-5p and miRNA-5189-5p are of high value in predicting the prognosis of elderly prostate cancer patients after LRP.

Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.