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.

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.

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.

Objective:To investigate the differences in electroencephalographic (EEG) microstate characteristics between children with autism spectrum disorder (ASD) and typically developing (TD) children, and to explore the correlation between irritability and EEG microstate features in ASD children.Methods:A total of 104 children with ASD [ASD group, 83 boys, 21 girls; aged 4-13 years, mean age (9.47±1.74)years] from the Autism Cohort of Nanjing Medical University and 60 TD children [TD group; 50 boys, 10 girls; aged 5-13 years, mean age(9.86±1.78) years ]from the IEEE Dataport database were enrolled. Irritability severity was assessed using the Affective Reactivity Index-Parent (ARI-P). Resting-state EEG data with eyes closed were recorded using a 24-channel dry-electrode EEG cap. Group-level EEG microstate topographic maps and microstate parameters, including mean duration, frequency, and time coverage, were extracted and compared between groups using nonparametric tests. In the ASD group, Spearman correlation analysis was used to examine the associations between microstate features and ARI-P in ASD children. Multiple linear regression was used to identify predictors of irritability.Results:Four group-level microstates (A, B, C, D) were identified in both groups. Compared to TD children, ASD children exhibited significantly longer mean duration for all microstates, in microstates A[ M(Q1, Q3)]: 0.060 (0.054,0.070) vs 0.091 (0.0530, 0.155) s, microstate B: 0.059 (0.050, 0.066) vs 0.087 (0.057,0.149) s, microstate C: 0.059 (0.050, 0.066) vs 0.095 (0.056, 0.183) s and microstate D: 0.055 (0.049,0.075) vs 0.095 (0.053,0.162) s ( Z=-3.51, -4.89, -4.71, -4.21; all P<0.001); However, microstate occurrence frequencies were significantly lower in the ASD group: A: 5.423 (3.640,21.024) vs 1.834 (1.327,3.395) Hz, microstate B: 4.949 (3.439,20.038) vs 2.146 (1.314,3.834) Hz, microstate C: 5.888 (3.998,22.078) vs 2.234 (1.441,3.768) Hz and microstate D: 5.371 (3.170,15.208) vs 2.074 (1.147,3.582) Hz ( Z=-7.72, -6.41, -7.85, -6.60; all P<0.001). In the ASD group, ARI-P scores were positively correlated with the mean duration of microstates B, C, and D ( r=0.28, 0.26, 0.33; all P<0.05) and negatively correlated with the occurrence frequency of microstates A, C, and D ( r=-0.26, -0.27, -0.21; all P<0.05). Multiple linear regression analysis revealed that the mean duration of microstate B was a significant predictor of irritability severity ( β=0.436, 95% CI: 1.260-4.202, P<0.001). Conclusion:Resting-state EEG microstate characteristics in Children with ASD differ from those in TD children and are associated with the severity of irritability. Prolonged duration of microstate B may serve as a risk factor for increased irritability in children with ASD.

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 investigate the value of 0.55 T MRI scanner using deep-learning (DL) reconstruction in evaluating pulmonary tumors.Methods:The study was a cross-sectional study. Sixty-one patients with pulmonary tumors on CT images were prospectively collected from May to September 2024 in Peking University First Hospital, including 37 males and 24 females, and aged 46?89 (68±9) years old. All patients underwent lung scan on a 0.55 T MRI, using diffusion weighted imaging(DWI) sequence with b-values of 0 and 800 s/mm 2. According to whether DL reconstruction was used and the number of acquisitions, they were divided into DWI-DL 5∶30 group (DL, number of averages=10, acquisition time=5 min 30 s),DWI-DL 3∶22 group (DL, number of averages=5, acquisition time=3 min 22 s), and DWI-C group (GRAPPA, number of averages=10, acquisition time=5 min 30 s). The obtained images were evaluated subjectively (Likert score) and objectively [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)]. Meanwhile the apparent diffusion coefficient (ADC) value of the tumors was measured. Friedman nonparametric test was used for comparison among the three groups and Bonferroni method was used for pairwise comparison. Results:The subjective scores, SNR, and CNR were significantly different among DWI-DL 5∶30 group, DWI-DL 3∶22 group, and DWI-C group( χ 2=9.69,87.56,88.62, P=0.008,<0.001,<0.001). Bonferroni method results showed that the subjective scores, SNR, and CNR of DWI-DL 5∶30 group were higher than those of DWI-DL 3∶22 group and DWI-C group ( P<0.05); However, the subjective scores, SNR, and CNR did not significantly differ between DWI-DL 3∶22 group and DWI-C group ( P>0.05). The ADC values of the tumors were not significantly different among DWI-DL 5∶30 group, DWI-DL 3∶22 group, and DWI-C group (χ 2=5.95, P=0.510). Conclusion:The DWI reconstructed using DL has better or similar image quality to conventional DWI in evaluating pulmonary tumors and significantly reduces scanning time, which has certain clinical application value.

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.

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.