Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

High-field magnetic resonance imaging (MRI), typically referring to systems with a magnetic field strength of ≥ 3 Tesla (T), offers significant advantages over conventional MRI in terms of higher signal-to-noise ratio (SNR) and improved resolution. These advantages have opened new prospects for the assessment of kidney diseases. This review summarizes the application progress of high-field MRI in evaluating kidney diseases, focusing on advanced techniques for refined assessment of renal anatomy and function, including arterial spin labeling (ASL) perfusion imaging, blood-oxygen-level-dependent (BOLD) oxygenation imaging, sodium (23Na) imaging, and quantitative evaluation of renal fibrosis. Furthermore, the review explores the value of high-field MRI in the diagnosis of renal tumors and kidney stones, tumor characterization, and its role in supporting treatments such as percutaneous nephrolithotomy (PCNL). Specifically, high-field MRI provides new approaches for early diagnosis and accurate staging of renal tumors, as well as radiation-free detection, composition analysis, and preoperative planning for PCNL in kidney stones. Finally, the review discusses current technical challenges, practical issues such as equipment accessibility, and future development directions. High-field MRI is emerging as a powerful non-invasive tool, providing crucial support for improving the diagnosis, management, and research of kidney diseases.

Objective To construct a combined model integrating ultrasonic features and radiomics derived from ultrasound images,and to evaluate its diagnostic performance in re-assessing the benign or malignant nature of Bethesda Ⅲ nodules.Methods A retrospective study was carried out on 442 patients with thyroid nodules classified as Bethesda Ⅲ after fine-needle aspiration biopsy(FNAB)between January 2019 and September 2024.All patients had undergone surgical pathology.The patients were randomly allocated into a training set and a testing set at a ratio of 7∶3.Relevant clinical characteristics were gathered,and regions of interest(ROI)were outlined on the most suspicious slice of the lesion prior to biopsy.Ultrasound radiomics features were extracted,key radiomics features were selected,and radiomics scores(Rad-score)were computed.The ultrasound model,radiomics model,and combined model were constructed.Subsequently,the diagnostic efficacy and clinical application value of each model were evaluated using the area under the receiver operating characteristic curve(AUC)and decision curve analysis(DCA).Results Univariate analysis and multivariate logistic regression analysis findings indicated that microcalci-fication,irregular margin,and Rad-score were independent risk factors for the malignant transformation of BethesdaⅢ nodules.In the testing set,the AUC values of the ultrasound model,radiomics model,and combined model were 0.76,0.71,and 0.81,respectively.The calibration curve of the combined model revealed a good consistency between the predicted values and the actual outcomes.The DCA of the testing set demonstrated that the combined model exhibited high clinical utility.Conclusion The combined model,established based on ultrasonic features and ultrasound radiomics,provides a higher predictive value for evaluating the malignancy risk of Bethesda Ⅲ nodules.

Objective To investigate the clinical effect of shoulder arthroscopic rotator cuff repair combined with shoulder three needles in treatment of rotator cuff injury.Methods 86 patients with rotator cuff injury from June 2021 to May 2023 were divided into two groups using a random number table method.The research group received 43 cases of rotator cuff repair under arthroscopy combined with shoulder three needles rotator cuff repair,while the control group received 43 cases of rotator cuff repair under arthroscopy combined with placebo needling.Then compare the pain level,shoulder joint function,and shoulder joint range of motion between the two groups before and 6 months after surgery,and calculate the excellent and good shoulder joint function rates between the two groups at 6 months after surgery,and compare the changes in inflammatory factors between the two groups at before and 4 weeks after surgery.Results 6 months after surgery,the visual analogue scale(VAS)score of both groups was lower than that before surgery,and the VAS score in research group(including the moderate tearing subgroup and the major tearing subgroup)was lower than that of the control group(including the moderate tearing subgroup and the major tearing subgroup),while the American Shoulder and Elbow Surgeons(ASES)score and shoulder joint range of motion were higher than those before surgery,and the ASES score and shoulder joint range of motion in research group(including the moderate tearing subgroup and the major tearing subgroup)were higher than those of the control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).6 months after surgery,the excellent and good rate of shoulder joint function in the research group was higher than that in the control group,the difference was statistically significant(P＜0.05).At 4 weeks after surgery,the levels of tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),and interleukin-8(IL-8)in both groups were lower than those before surgery,and the research group(including the moderate tearing subgroup and the major tearing subgroup)were lower than those of control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).Conclusion Arthroscopic rotator cuff repair combined with shoulder three needles can alleviate the pain level of patients with rotator cuff injury,improve shoulder joint function and range of motion,increase the excellent and good rate of shoulder joint function,and reduce inflammatory reaction.It is worthy of clinical application.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

Objective This study aimed to explore the ability of ultrasonographic radiomics in predicting the occurrence of in-stent restenosis(ISR)after carotid artery stenting(CAS)by analyzing the correlation between radiomic features of responsible plaques in carotid artery stenosis and the incidence of ISR.Methods A retrospective collection was conducted on 206 cases that underwent CAS treatment at our hospital.The enrolled patients were randomly split into a training set(144 cases)and a test set(62 cases)at a 7∶3 ratio.We utilized the Darwin Intelligent Research Platform to extract radiomic features from each region of interest,and then screened 1125 ultrasonographic radiomic features.Different machine learning algorithms were employed to construct diagnostic models,and the best-performing classifier was selected.Various prediction models were established,including a clinical-ultrasonographic feature model,a radiomic model,and a combined clinical-ultrasonographic-radiomic model.Results Multivariate logistic regression analysis in the training set revealed that hypertension,hyperuricemia,triglycerides,and plaque location were independent risk factors for ISR after CAS.For the clinical-ultrasonographic model,the area under the curve(AUC)values for the training and validation sets were 0.896 and 0.644,respectively.The corresponding AUC values for the radiomic model were 0.961 and 0.715,while those for the combined model were 0.947 and 0.727.Conclusion The radiomic model demonstrates superior performance in predicting ISR compared to the traditional clinical-ultrasonographic model.The combined model exhibited an enhanced ability to predict ISR occurrence,thereby improving the diagnostic performance of traditional assessments.

Objective:To explore the diagnostic value of blood flow parameters of carotid ultrasound combined with serum Sortilin and paraoxonase-1 (PON-1) for stability of carotid atherosclerotic plaque (CAP). Methods:A total of 100 CAP patients who admitted to Rugao Hospital of Traditional Chinese Medicine from January 2021 to December 2023 were selected,and they were divided into a stable plaque group (n=54) and a unstable plaque group (n=46). Enzyme linked immunosorbent assay (ELISA) was adopted to determine the expression levels of serum Sortilin and PON-1 of patients in two groups. Multi factor logistic regression was implemented to analyze the influencing factors on CAP stability. The receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic efficiency of blood flow parameters of carotid ultrasound combined with Sortilin and PON-1 on CAP stability. Results:Compared with the end diastolic blood flow velocity (EDV) and intima-media thickness (IMT) of stable plaque group,unstable plaque group showed increased EDV and IMT,and decreased PSV,and the differences were significant (t=7.536,4.680,5.487,P<0.05),respectively. Compared with stable plaque group,the serum Sortilin level in unstable plaque group significantly increased,while the PON-1 level significantly decreased,and the differences of them were significant (t=8.362,5.581,P<0.05),respectively. Multivariate logistic analysis found that Sortilin was a risk factor that affected CAP stability (OR=3.165,P<0.05),while PON-1 was a protective factor that affected CAP stability (OR=0.765,P<0.05). ROC curve analysis indicated that the area under curve (AUC) values of single Sortilin,PON-1,EDV,IMT,PSV,and the combination of them were respectively 0.788 (95％CI:0.695-0.864),0.814 (95％CI:0.724-0.885),0.847 (95％ CI:0.761-0.911),0.767 (95％ CI:0.672-0.846),0.707 (95％ CI:0.607-0.793) and 0.963 (95％ CI:0.839-0.907). The AUC value of the combination of above 5 indicators was highest,which was better than that of each single indicator,and its sensitivity and specificity were respectively 95.65％ and 83.33％. Conclusion:The EDV,IMT and PSV of blood flow parameters of ultrasound can provide CAP information of morphology and hemodynamics,and serum Sortilin level and PON-1 level can reflect the biological processes of formation and development of CAP. The combined detection of the five indicators can better diagnose CAP stability.

Objective To investigate the clinical effect of shoulder arthroscopic rotator cuff repair combined with shoulder three needles in treatment of rotator cuff injury.Methods 86 patients with rotator cuff injury from June 2021 to May 2023 were divided into two groups using a random number table method.The research group received 43 cases of rotator cuff repair under arthroscopy combined with shoulder three needles rotator cuff repair,while the control group received 43 cases of rotator cuff repair under arthroscopy combined with placebo needling.Then compare the pain level,shoulder joint function,and shoulder joint range of motion between the two groups before and 6 months after surgery,and calculate the excellent and good shoulder joint function rates between the two groups at 6 months after surgery,and compare the changes in inflammatory factors between the two groups at before and 4 weeks after surgery.Results 6 months after surgery,the visual analogue scale(VAS)score of both groups was lower than that before surgery,and the VAS score in research group(including the moderate tearing subgroup and the major tearing subgroup)was lower than that of the control group(including the moderate tearing subgroup and the major tearing subgroup),while the American Shoulder and Elbow Surgeons(ASES)score and shoulder joint range of motion were higher than those before surgery,and the ASES score and shoulder joint range of motion in research group(including the moderate tearing subgroup and the major tearing subgroup)were higher than those of the control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).6 months after surgery,the excellent and good rate of shoulder joint function in the research group was higher than that in the control group,the difference was statistically significant(P＜0.05).At 4 weeks after surgery,the levels of tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),and interleukin-8(IL-8)in both groups were lower than those before surgery,and the research group(including the moderate tearing subgroup and the major tearing subgroup)were lower than those of control group(including the moderate tearing subgroup and the major tearing subgroup),the differences were statistically significant(P＜0.05).Conclusion Arthroscopic rotator cuff repair combined with shoulder three needles can alleviate the pain level of patients with rotator cuff injury,improve shoulder joint function and range of motion,increase the excellent and good rate of shoulder joint function,and reduce inflammatory reaction.It is worthy of clinical application.

With the change of infectious disease incidence pattern and the development of related technologies, progresses have been made in the research of infectious disease epidemiology. In recent years, due to the change in the requirements of infectious disease prevention and control, the research focus has expanded from common infectious diseases to diseases which have been eliminated or might be eliminated, as well as emerging and re-emerging infectious diseases. Infectious disease data has been characterized by multiple sources and modalities. Along with the rapid development of pathogen detection methods, infectious disease surveillance has shifted from a single disease-targted one to a comprehensive one. Moreover, novel technologies such as multi-omics and artificial intelligence have been applied in infectious disease epidemiology research. The international cooperation in this field has become increasingly crucial, and the revision of the International Health Regulations and the negotiation of pandemic agreement will have a profound impact. In the future, infectious disease epidemiology research will develop with more powerful tools to improve its capabilities.

Diabetic nephropathy(DN),a primary cause of end-stage renal disease(ESRD)in diabetic patients,is pathologically characterized by chronic inflammation and renal fibrosis.Chronic inflammation promotes renal cellular damage,epithelial-mesenchymal transition,and extracellular matrix(ECM)accumulation through mechanisms including immune cell activation,pro-inflammatory cytokine secretion,and initiation of multiple sig-naling pathways.Excessive ECM deposition disrupts renal architecture and drives tubulointerstitial expansion,thereby accelerating renal functional decline.Recent studies demonstrate that chronic inflammation and fibrosis synergistically propagate DN progression via bidirectional crosstalk.Inflammation serves as an early driver of fibro-genesis and further amplifies fibrotic processes through positive feedback mechanisms,establishing a self-perpetu-ating inflammation-fibrosis vicious cycle.However,the precise molecular interplay between chronic inflammation and fibrosis remains incompletely elucidated.Thus,in-depth exploration of their interaction mechanisms is crucial for developing novel DN interventions.This review delineates the pathogenic roles of chronic inflamma-tion and fibrosis in DN to advance mechanistic understanding and provide foundational insights for designing in-novative therapeutic strategies.