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.

Objective To investigate the predictive value of serum lactate dehydrogenase(LDH)level com-bined with high-throughput sequencing in children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods The clinical data of 99 children with Mycoplasma pneumoniae pneumonia(MPP)admitted to Hua-zhong University of Science and Technology Union Hospital from October 2023 to March 2024 were retro-spectively analyzed.According to the severity of the disease,the children were divided into mild group(33 ca-ses)and severe group(66 cases).Spearman correlation analysis was used for correlation analysis,Logistic re-gression was used to analyze the influencing factors of SMPP,and the receiver operating characteristic(ROC)curve was used to evaluate the value of LDH in predicting SMPP.Results The level of LDH in the severe group was higher than that in the mild group(P<0.05).The results of high-throughput sequencing showed that the proportions of virulence positive and drug resistance gene A2063G mutation in the severe group were higher than those in the mild group(P<0.05).Multivariate Logistic regression analysis showed that LDH level and drug resistance gene A2063G mutation were related to the SMPP(P<0.05).ROC curve analysis showed that LDH combined with high-throughput sequencing detection of drug resistance gene A2063G muta-tion had a high value in predicting SMPP,and the area under the curve was 0.724.Conclusion Serum LDH combined with high-throughput sequencing detection of drug resistance gene A2063G mutation can be used as an effective indicator to predict SMPP.

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.

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.

Urolithiasis represents a prevalent clinical challenge marked by high recurrence rates and morbidity，with existing preventive strategies struggling to effectively curb its epidemic trajectory，thereby posing a significant threat to public health. The etiology of this condition is intricate，involving a complex network of interactions spanning classical supersaturation-crystallization theory，Randall’s plaque theory，and multifactorial elements such as cellular injury，inflammatory responses，metabolic derangements，the gut-kidney axis，immune dysregulation，and genetic predisposition. However，the critical mechanisms initiating stone formation and the early pathophysiological processes remain incompletely elucidated，constituting the core impasse in current preventive strategies. This review systematically synthesizes classical theories and cutting-edge advancements in urolithiasis etiology research，emphasizing the urgent need to integrate emerging technologies，including high-dimensional omics，advanced imaging modalities，and artificial intelligence，to dissect pivotal pathological nodes in early stone formation. Such interdisciplinary efforts are essential to overcome cognitive bottlenecks and ultimately achieve personalized，precision-based prevention strategies.

Objective:To explore the preliminary results of using the UreteroPyeloVisClear Catheter (VCC) in the treatment of ureteral stones.Methods:A retrospective analysis was conducted on the clinical data of 18 patients with ureteral stones who underwent treatment with VCC at Beijing Tsinghua Changgung Hospital from November 2023 to March 2024. The cohort consisted of 15 men and 3 women, with a mean age of 53 years (range: 27-75 years). The preoperative CT measurements showed that the mean maximum stone diameter was 9 mm (range: 3-18 mm), and the mean maximum CT value of the stones was 870 HU (range: 260-1 480 HU). The distribution of stones was as follows: 3 cases in the upper ureter, 8 in the middle ureter, and 7 in the lower ureter. Gravity-assisted perfusion was used, and all patients underwent VCC combined with Holmium laser lithotripsy, with flexible ureteroscopy used if necessary. A ureteral stent was routinely placed for 2 weeks postoperatively. Perioperative conditions and complications were analyzed.Results:All 18 patients successfully underwent VCC lithotripsy, with one patient experiencing stone migration during the procedure. The average operation time was 53 minutes (range: 20-100 minutes), and the average lithotripsy time was 25.5 minutes (range: 6–60 minutes). There were no significant changes in serum creatinine or hemoglobin levels on the first postoperative day. The average hospital stay was 2 days (range: 1–3 days). One patient experienced a fever (maximum temperature of 38.5℃), which resolved with antibiotic treatment. The visual analogue scale (VAS) scores on postoperative day 1 were 0 for 15 patients, 2 for 1 patient, 3 for 1 patient, and 4 for 1 patient. No complications of Clavien-Dindo grade Ⅱ or higher were observed. At 1-month follow-up, the stone-free rate (SFR) was 100%(18/18), and no hydronephrosis was observed in the affected kidney.Conclusions:The results of this study indicates that VCC is a safe and effective method for treating ureteral stones, with a low incidence of postoperative complications and a high stone clearance rate.

Kidney stone is a common urological disorder with an increasing annual incidence，posing a heavy social burden. Previous studies have demonstrated that diverse cell death modalities，including ferroptosis and apoptosis，induce renal tubular epithelial cell injury and thereby promote kidney stone formation. Emerging evidence in recent years has further revealed that immune-inflammatory responses driven by interactions among renal microenvironment components also contribute to kidney stone pathogenesis. This review systematically summarizes current research advances on the mechanisms by which inflammatory cellular components（e.g.，macrophages，T cells），inflammatory mediators（e.g.，inflammasomes，cytokines），microbiota，and their synergistic interactions influence kidney stone development within the renal microenvironment.