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.

Objective To explore the changes in intrarenal pelvic pressure and intrarenal temperature during F6.3 disposable electronic ureteroscopic lithotripsy through in vitro experiments. Methods Microchannels were established in the upper, middle, and lower calyces of ex vivo porcine kidneys. Spherical calcium oxalate stones(size:0.5 cm×0.5 cm×0.5 cm, 1-2 per target calyx)were placed via the microchannels. Temperature and pressure sensors were connected through sheaths and placed in each calyx. F6.3 disposable electronic ureteroscope combined with super-pulsed thulium fiber laser(pulse energy:0.1 J, frequency:300 Hz, power:30 W)was used for laser lithotripsy. During the procedure, normal saline(25±1)℃ was used for irrigation at a gradient of 10-150 mL/min(increasing by 10 mL/min). The temperature and pressure in the upper, middle, and lower calyces were observed and recorded at different irrigation flow rates, with each experiment repeated five times, and the average value was calculated. The intrarenal temperature and pressure changes within and between the three groups were compared. Results In the ex vivo porcine kidney model, intrarenal pelvic pressure increased linearly with the increase in irrigation flow rate. When the flow rate reached 90 mL/min, the average intrarenal pelvic pressure was(28.8±1.16)mmHg. When the flow rate was increased to 100 mL/min, the pressure exceeded the safety threshold, reaching(31.23±1.12)mmHg. With the increase in irrigation flow rate, intrarenal temperature gradually decreased. When the flow rate reached 20 mL/min, the maximum intrarenal temperature was 45.1 ℃. When the flow rate was increased to 30 mL/min, the maximum intrarenal temperature was 40.9 ℃, which did not exceed the safety threshold(43 ℃). Conclusion The in vitro experiments demonstrated that during F6.3 disposable electronic ureteroscopic lithotripsy, maintaining an irrigation flow rate of 30-90 mL/min kept the intrarenal pelvic pressure and intrarenal temperature within the safety thresholds, indicating that the procedure is safe and reliable.

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.

Super-pulse thulium fiber laser (hereinafter referred to as thulium laser) has shown broad application prospects in medical research, especially in the treatment of urinary tract stones.Thulium laser has a thin fiber diameter, which reduces the occupation of the working channel and increases the irrigation water flow.Currently, the peak power reaches up to 500 W, the single pulse energy to 6 J, and the frequency to 2000 Hz.The stone-breaking mechanism of thulium laser is photothermal and photomechanical.Different combinations of energy and frequency will significantly affect the volume of stone fragments. "High energy and low frequency" is more suitable for "fragmentation" stone breaking, while "low energy and high frequency" is more suitable for "powderization" stone breaking.Some in vitro experiments have confirmed that thulium laser has higher stone-breaking efficiency, less stone displacement, and more obvious thermal effects compared to holmium laser.Clinically, thulium laser has been applied to ureteroscopic lithotripsy and percutaneous nephrolithotomy., and the stone free rate and safety are relatively high.This article reviews the stone-breaking principles, in vitro experiments, and clinical applications of thulium laser, aiming to provide better theoretical support and practical experience for the development and application of super-pulse thulium fiber laser in the future.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

OBJECTIVE To establish the fingerprint of Gerbera delavayi and the methods for the content determination of 11 components in G. delavayi. METHODS High-performance liquid chromatography（HPLC）was adopted to establish the fingerprints of 13 batches of G. delavayi（No. S1-S13）， and the similarities were evaluated according to Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）， while the common peaks were identified. Hierarchical clustering analysis （HCA）， principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were carried out by using SPSS 25.0 software and SIMCA 14.1 software. The contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， 3，8-dihydroxy-4-methoxy-2-oxo-2H-1-benzopyran-5-carboxylic acid， caffeic acid， 3-hydroxy-4-methoxy-2- oxo-2H-1-benzopyran- 5-carboxylic acid， luteolin-7-O-β-D-glucoside， isochlorogenic acid A， apigenin-7-O-β-D-glucoside， isochlorogenic acid C and xanthotoxin were determined by HPLC. RESULTS The similarities in HPLC fingerprint of 13 batches of G. delavayi were 0.801-0.994； a total of 38 common peaks were identified and 13 common peaks were identified. The results of HCA showed that S1-S5 and S7 were clustered into one group， S6 into one category， S8 into one category， S9 and S11 into one category， S10， S12 and S13 into one category， and the results of PCA were consistent with them. The results of OPLS-DA showed that variable importance values for the projection of peak 7 （chlorogenic acid）， peak 21 （isochlorogenic acid A）， peak 26 （xanthotoxin）， peak 19 （isochlorogenic acid B）， peak 33， peak 13， peak 23 （isochlorogenic acid C）， peak 2 （new chlorogenic acid）， peak 17 （luteolin-7-O-β-D- glucoside） were greater than 1. The above 11 components had good linearity in their respective detection concentration ranges （r was greater than 0.999）. RSDs of precision， repeatability， and stability tests were not more than 2% （n＝6）. The average recovery rates were 92.54%-105.55%， and the RSDs were 0.83%-1.93% （n＝6）. The average contents of 11 components were 0.744， 5.014， 0.646， 0.431， 0.069， 0.582， 0.979， 2.754， 0.157， 1.284 and 2.943 mg/g， respectively. CONCLUSIONS The constructed HPLC fingerprint and content determination methods are simple， accurate and stable， which can provide reference for quality control of G. delavayi. Xanthotoxin， chlorogenic acid， isochlorogenic acid A， luteolin-7-O- β -D-glucoside， isochlorogenic acid C and new chlorogenic acid can be used as markers for G. delavayi.

Complex urinary stones have been the focus and difficulty of clinical treatment.Traditional multi-channel percutaneous nephrolithotomy (PCNL) has a high stone-free rate and efficacy in the treatment of multiple or large volume kidney stones，but has risk of serious complications such as bleeding and injury.Retrograde intrarenal surgery (RIRS) has been preferred in the treatment of renal stones with a diameter of less than 2 cm due to its characteristics of small trauma and fast recovery.However，it is difficult to treat small calyx stones with poor anatomy，lower renal calyx stones with small IPA，and diverticulum stones.Needle-perc assisted endoscopic surgery (NAES) includes the following modes：①Needle-perc plus PCNL，which can effectively reduce the number of channels，reduce surgical risks，and protect kidney function while ensuring a high stone-free rate; ②Needle-perc plus RIRS，which can significantly improve the success rate and stone-free rate without increasing kidney damage，thus having significant advantages in dealing with complex urinary stones.In order to popularize and promote this technique，this essay will review the relevant domestic and foreign literature and the clinical experience of our center，focusing on the indications，usage specifications，operative skills and precautions of NAES.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

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.