Objective To identify core targets of hepatocellular carcinoma (HCC) by using bioinformatics and specific algorithms, explore their relationships with immune cells, and investigate the causal relationships between immune cells and HCC through Mendelian randomization. Methods Relevant genes associated with the development of HCC were screened using the GEO and TCGA databases. Immune infiltration analysis was conducted using GSVA and CIBERSORT algorithms. A bidirectional Mendelian randomization analysis was then performed to explore the causal relationships between immune cells and HCC. Results A total of 284 HCC-related genes were identified, with 120 genes recognized within the protein interaction network. Immune infiltration analysis revealed significant correlations between key genes and immune cells. Mendelian randomization results indicated that HLA DR on CD33⁺ HLA DR⁺ CD14dim (OR=1.097, 95%CI: 1.002–1.201, P=0.045, P_Bonferroni=0.091) and CD8 on CD28⁺ CD45RA⁺ CD8⁺ T cell (OR=1.123, 95%CI: 1.027–1.228, P=0.011, P_Bonferroni=0.022) were the risk factors for HCC. Conversely, HLA DR⁺⁺ monocyte absolute count was identified as a protective factor for HCC (OR=0.812, 95%CI: 0.702–0.938, P=0.005, P_Bonferroni=0.139). Conclusion The occurrence and development of liver cancer may be related to CDK1, CCNB1, and CDC20, showing a high degree of correlation with Th2 cells, T helper cells, Th17 cells, and DCs. Mendelian randomization shows that HLA DR on CD33⁺HLA DR⁺ CD14dim and CD8 on CD28⁺CD45RA⁺CD8⁺T cells are associated with an increased risk of HCC. The risk of hepatocellular carcinoma is associated with a decrease in the level of HLA DR⁺⁺monocyte absolute count.

Lung cancer (LC) complicated with interstitial lung disease (ILD) is a relatively common comorbidity in clinical practice, and its management remains complex and challenging. As one of the primary treatment modalities for LC, radiotherapy carries a risk of inducing acute exacerbation of ILD and severe radiation pneumonitis; therefore, it should be used with caution in LC-ILD patients. Advances in radiotherapy technology now allow for more precise tumor targeting and better sparing of healthy lung tissues, potentially offering greater therapeutic benefits for these patients. In this article, current status and recent research progress in the application of radiotherapy in LC-ILD were reviewed, aiming to provide theoretical basis and reference for clinical practice.

Accurate identification of endogenous and exogenous substances in food,particularly in competition supplies,is crucial for ensuring food safety and fair competition,as well as for protecting the legitimate rights and professional reputations of athletes.Testosterone(T)and dehydroepiandrosterone(DHEA)are important steroid hormones that can stimulate protein synthesis,increase the number and volume of muscle cells,and promote muscle growth and recovery.Both are often illegally used in the animal husbandry industry to promote animal growth and improve meat quality.However,current research in this area remains limited,and identification technologies require further investigation.This study focused on the techniques for identifying endogenous and exogenous hormones including T and DHEA in beef.A Soxhlet extraction method was established,reducing the pretreatment cycle to 110 min while achieving high extraction efficiency,with recovery rates of 102.5%for T and 91.9%for DHEA,respectively.Based on this,a gas chromatography-combustion-isotope ratio mass spectrometry(GC-C-IRMS)method was developed for analyzing carbon isotopes in T and DHEA,eliminating the need for derivatization.By adding reference materials to the extract,simultaneous measurement of reference materials and target analytes was achieved.The measurement of caffeine reference material,T and DHEA was completed within 40 min,with a measurement repeatability of 0.02‰.Theδ13C values of T and DHEA in standard substances,which may serve as exogenous additives,were determined using elemental analysis-isotope ratio mass spectrometry(EA-IRMS).The results indicated an average δ13C value of-29.44‰±0.81‰(k=1)for 10 T standards and-30.86‰±0.87‰(k=1)for 14 kinds of DHEA standards.This approach effectively distinguished between endogenous sources and exogenous addition of these two hormones in beef,thereby providing vital technical support for the assurance and supervision of food safety.

Objective To identify the key factors affecting the risk of medical surges and their coupling relation5 ships,providing strategic support for medical institutions to optimize risk management and emergency governance.Methods 17 influencing factors were determined based on WSR theory,and an expert scoring method was employed to assess the impact strength among the factors.The DEMATEL method was applied to calculate the centrality,cau5 sality,influence,and being influenced degrees of the influencing factors.The ISM method was used to construct a hierarchical structure of the influencing factors related to medical surge risks,thereby revealing the connections and interaction mechanisms among these factors.Results Seven critical influencing factors were identified,including the crisis decision-making capacity and leadership effectiveness of emergency managers,the completeness of the emer5 gency system and dynamic execution capabilities,and the cross-departmental coordination mechanism and com5 mand collaboration efficiency.Deep driving factors and coupling pathways were also revealed.Conclusion The risk of medical surges exhibits multi-factorial coupling cascade effects;attention should be directed towards the construc5 tion of mid-to-deep level mechanisms such as information systems,institutional frameworks,and organizational management,to enhance targeted capabilities and systemic resilience in risk governance.

Objective To explore the coupling mechanism between medical surge response resources and the spread of secondary risks during public health emergencies,as well as the effectiveness of relevant interventions.Methods Based on complex network theory,a dual-layer network model of medical resources and secondary events was constructed.The interactive feedback between medical resource status and secondary event risk,as well as the effects of network structure,were analyzed through MATLAB simulations,REPAST agent-based modeling,and mean-field analysis.Results Simulation and prediction results show that an increase in first-layer resource-deficient nodes significantly raises the activation rate and transmission speed of secondary events,while the clustering and spread of secondary events in the second layer,in turn,intensify resource depletion,creating a negative feedback loop.Mean-field analysis indicates a nonlinear positive correlation between the adequacy of medical resources and the likelihood of secondary events.Network structure analysis reveals that when the average node degree exceeds 8,resource allocation efficiency improves markedly.Conclusion There exists a dynamic coupling and bidirectional feedback relationship between medical resource status and secondary event risks.Enhancing the flexible allocation and responsiveness of medical resources,improving multi-sectoral collaborative monitoring and coordinated regulation,optimizing network connectivity and coordination mechanisms for resource distribution,and establishing dynamic monitoring and tiered early warning systems are key strategies for strengthening the resilience of healthcare systems and effectively containing the spread of secondary events.

Objective:To analyze the clinical and ultrasonographic characteristics of papillary thyroid carcinoma(PTC)and explore their correlation with cervical lymph node metastasis(CLNM),thereby constructing a nomogram pre-diction model for assessing the risk of CLNM in PTC.Methods:A total of 553 patients(corresponding to 553 nod-ules)with papillary thyroid carcinoma(PTC),confirmed by postoperative pathology,who underwent ultrasonography and had complete clinical data at the Second Hospital of Shandong University between December 2019 and December 2022,were included.228 patients(228 nodules)hadcervical lymph node metastasis,and 325 patients(325 nodules)were without cervical lymph node metastasis.All patients were categorized into metastasis and non-metastasis groups based on the presence or absence of cervical lymph node metastasis.These groups were then randomly di-vided into training and validation sets in a 7:3 ratio.Differences in clinical and ultrasonographic characteristics between the two groups were compared,and a nomogram was constructed.Results:Univariate analysis revealed statistically significant differences between the metastasis group and the non-metastasis group in terms of age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,capsular contact,and blood flow(P<0.05).Logistic regression analysis in the training set indicated that age,presence of Hashimoto's thyroiditis,multifocality,taller-than-wide shape,calcification,and blood flow were associated with lymph node metastasis in papillary thyroid carcinoma(PTC)(P<0.05).These indicators were incorporated into a nomogram model,which demonstrated high predictive performance,good calibration,and significant clinical utility in both the training and validation sets.Conclu-sion:The nomogram prediction model,constructed based on clinical and ultrasonographic features,effectively predicts the risk of cervical lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC).Patients who were older,had concomitant Hashimoto's thyroiditis,or exhibited a nodule aspect ratio≥1 were less likely to have concurrent CLNM.Conversely,patients presenting with multiple nodules,nodules with microcalcifications,or nodules demonstrating central or rich/peripheral vascularity were more likely to have concurrent CLNM.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To investigate the effect of miR-7975 on the malignant phenotype of oral squamous cell carcinoma(OSCC)and its potential mechanisms.Methods This study compared the expression levels of miR-7975 in different oral cell lines by qRT-PCR.miR-7975 mimic and miR-7975 inhibitor were transfected into OSCC cell lines HSC3 and HN4 respectively.Colony formation as-say,CCK8 assay,Transwell assay,and wound healing assay were conducted to evaluate the effects of miR-7975 on the malignant phe-notype of OSCC cells.Western blot was employed to analyze changes in the expression of EMT related proteins and proteins associated with the RAS/ERK signaling pathway.Subcutaneous tumor model of nude mice was used to further validate the tumorigenic effect of miR-7975 in vivo.Results The expression of miR-7975 was downregulated in OSCC cells.Overexpression of miR-7975 reduced the proliferation,migration,and invasion abilities of OSCC cells,whereas downregulation of miR-7975 enhanced these abilities.After miR-7975 overexpression,the expression of the EMT-related protein E-cadherin was upregulated,while N-cadherin,Vimentin,β-catenin,Snail,and Slug were downregulated.Additionally,the expression of proteins related to the RAS/ERK signaling pathway increased.Conversely,the expression of EMT and RAS/ERK signaling pathway-related proteins showed opposite changes when miR-7975 was downregulated.Compared to the control group,the volume and weight of tumors formed in nude mice were significantly smaller after miR-7975 overexpression,while they were significantly larger when miR-7975 expression was reduced.Conclusion miR-7975 exerts its tumor-suppressive effects by inhibiting the proliferation,migration,and invasion of OSCC through the regulation of EMT and the RAS/ERK signaling pathway.

Aim To explore the effects of exercise during pregnancy on renal structure,function and angiotensin Ⅱ(Ang Ⅱ)/transforming growth factor-β1(TGF-β1)/connective tissue growth factor(CTGF)signaling pathway in 3-month-old offspring of spontaneously hypertensive rats(SHR),the aim of this study was to provide experimental basis for early intervention of hypertension and protection of key target organs.Methods After mating SHR and WKY rats,pregnant rats were randomly divided into sedentary group(p-WKY-SED,p-SHR-SED)and exercise group(p-WKY-EX,p-SHR-EX).Blood pressure,serum urea nitrogen and creatinine were measured by caudal artery non-invasive blood pressure system and colorimetry in 3-month-old offspring rats.HE staining,Masson staining,ELISA and Western blot were used to detect the renal structure,collagen volume fraction,Ang Ⅱ concentration,renin-angiotension-aldosterone sys-tem(RAAS)and protein expression related to fibrogenic signal pathway in 3-month-old rats.Results(1)The sys-tolic blood pressure(SBP),diastolic blood pressure(DBP)and mean arterial pressure(MAP)of offspring rats in p-SHR-SED group were significantly higher than those in p-WKY-SED group.The SBP,DBP and MAP of SHR male off-spring rats were significantly decreased by exercise during pregnancy(P＜0.05),but had no effect on the female offspring rats(P＞0.05).(2)There was no significant difference in serum urea nitrogen and creatinine among the groups(P＞0.05).(3)The glomerular volume and the collagen volume fraction in p-SHR-SED group were significantly higher than those in p-WKY-SED group(P＜0.05),and the glomerular volume and the collagen volume fraction in p-SHR-EX group were significantly lower than those in p-SHR-SED group(P＜0.05).(4)Renal Ang Ⅱ level of offspring rats in p-SHR-SED group was significantly higher than that in p-WKY-SED group,and renal Ang Ⅱ level of offspring rats in p-SHR-EX group was significantly lower than that in p-SHR-SED group(P＜0.05).(5)The expression levels of angiotensin Ⅱ type 1 receptor(AT1R),TGF-β1 and CTGF protein in p-SHR-SED group were significantly higher than those in p-WKY-SED group(P＜0.05),while the expression levels of angiotensin converting enzyme 2(ACE2),angiotensin Ⅱ type 2 receptor(AT2R)and MasR protein in p-SHR-SED group were significantly lower than those in p-WKY-SED group(P＜0.05).Conclusion(1)Exercise during pregnancy can significantly decrease the blood pressure of 3-month-old male offspring rats of hypertensive rats,but has no significant effect on that of 3-month-old female offspring.(2)Exercise during preg-nancy may reduce renal fibrosis in 3-month-old female/male offspring of hypertensive rats by regulating RAAS balance and inhibiting Ang Ⅱ/TGF-β1/CTGF signaling pathway.