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.

Hepatic alveolar echinococcosis is a highly invasive zoonotic parasitic disease with poor prognosis. Surgical intervention serves as the pivotal approach to achieve radical cure and improve the prognosis of hepatic alveolar echinococcosis patients. In recent years, with the popularization of the concept of precision surgery and the development of the multidisciplinary diagnosis and treatment model, the surgical treatment strategies for hepatic alveolar echinococcosis have been continuously enriched, and the selection of surgical procedures has become increasingly diversified. Although key surgical techniques such as radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation have achieved remarkable progress in clinical application, many insurmountable challenges still remain. Therefore, by sorting out the latest evidence-based advances in the field of surgical treatment for hepatic alveolar echinococcosis, this article focuses on discussing the application status and bottlenecks of radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation in hepatic alveolar echinococcosis, aiming to provide a reference for the clinical treatment of hepatic alveolar echinococcosis.

Objective To study the mini-character and microscopic features of Plantago asiatica from different populations and summarize the exclusive features to provide a reference for the effective identification of Plantago asiatica. Methods Stereomicroscope and optical microscope were used to identify 30 batches of Plantago asiatica from different populations.The similarities and differences in mini-character and microscopic features of Plantago asiatica among different populations were identified. Results The differences in mini character between the Plantago asiatica from different populations were mainly reflected in whether there was fluff on the surface of leaves, inflorescence peduncles, and persistent sepals, as well as whether the epidermis of fibrous roots was flaky. The differences in microscopic characteristics between the Plantago asiatica from different populations were mainly reflected in the number of non-glandular hairs on the leaf surface, the shape of the petiole endothelial layer cells, and the number of large vascular bundles, and the number of layers of mesophyll palisade tissue cells, etc. Conclusion Plantago asiatica from different populations can be identified through mini-character and microscopic; by comparing the relevant identification features, which can provide a basis for revising and improving the standards of Plantago asiatica.

Objective:To investigate the clinical value of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) in postoperative patients with stage Ⅲ colorectal cancer based on stress response indexes.Methods:A total of 86 patients with colorectal cancer treated in Mudanjiang Cancer Hospital and Hongqi Hospital Affiliated to Mudanjiang Medical College from January 2021 to January 2023 were retrospectively selected as the study objects, of which 43 patients underwent conventional laparoscopic radical resection of colorectal cancer (LCR) treatment (control group) and 43 patients underwent NOSES treatment (observation group). The changes of tumor markers, stress response indexes and humoral immunity indexes were compared between the two groups before and aftertreatment, and the incidence of postoperative complications were compared between the two groups.Results:The levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, CA242 and CA125 in the two groups were decreased 2 weeks after surgery ( P<0.05), but there were no statistical differences between the two groups ( P>0.05). The level of superoxide dismutase (SOD) in the observation group was higher than that in the control group 3 d after operation: (68.45 ± 8.30) kU/L vs. (59.64 ± 8.18) kU/L; the level of malondialdehyde (MDA) was lower than that in the control group: (8.84 ± 2.03) mmol/L vs. (10.26 ± 2.11)mmol/L, there were statistical differences ( P<0.05). The levels of immunoglobulin (Ig)A, IgM and IgG in the observation group were higher than those in the control group 3 d after operation: (1.59 ± 0.40) g/L vs. (1.33 ± 0.36) g/L, (1.25 ± 0.31) g/L vs. (1.03 ± 0.26) g/L, (8.75 ± 2.12) g/L vs. (6.89 ± 2.05) g/L, there were statistical differences ( P<0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P>0.05). Conclusions:Laparoscopic-assisted NOSES in the treatment of stage Ⅲ colorectal cancer can effectively improve the level of tumor markers of patients, reduce the stress reaction and immune damage caused by surgery to the patients and ensure the safety.

Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.

Purpose To explore the influence of thrombolysis therapy before percutaneous coronary intervention(PCI)on long-term left ventricular global and regional function in ST segment elevation myocardial infarction(STEMI)patients by cardiac magnetic resonance(CMR).Materials and Methods A retrospective analysis was conducted on 67 STEMI patients who were enrolled in a prospective study from November 2021 to August 2022 in the First Affiliated Hospital with Nanjing Medical University,the First People's Hospital of Lianyungang,the Affiliated Hospital of Jiangnan University,Changzhou No.2 People's Hospital and Huai'an Second People's Hospital and underwent CMR examination one year later.STEMI patients were divided into thrombolysis group and non-thrombolysis group according to whether a single half-dose of 5 mg recombinant staphylokinase(r-SAK)was given within two hours before the first medical contact and PCI.Based on CMR cine images,the traditional left ventricular function,global and segmental functional parameters were measured,and the differences between the two groups were compared.According to the degree of late gadolinium enhancement involvement,myocardial segments were divided into the following four types:transmural infarcted segments,non-transmural infarcted segments,locally infarcted segments,and non-infarcted segments.The parameters of the two groups were compared across these different segments.Results At the patient level,the cardiac index,left ventricular wall thickening and left ventricular wall motion in r-SAK thrombolysis group were higher than those in non-thrombolysis group(t/Z=-2.426,-4.307,-2.735,all P<0.05).At the segment level,compared with non-thrombolysis group,patients received r-SAK before primary PCI showed greater segmental radial strain in non-transmural infarcted segments(Z=-2.117,P=0.034);larger segmental wall motion in locally infarcted segments(Z=-2.235,P=0.025),and better segmental circumference strain in the non-infarcted segments(Z=-3.869,P<0.001).Conclusion The thrombolytic therapy before PCI in STEMI patients retain better long-term left ventricular global and regional function evaluating by CMR.

Objective:To explore the inhibitory effect of protocatechuic acid (PCA) on the growth of ovarian cancer cell line A2780 and its mechanism.Methods:A2780 cells were cultured in vitro and randomly divided into a control group and protocatechuic acid-treated groups with concentrations of 5 μM and 10 μM. Cell proliferation was detected using the MTT assay; Cell migration ability was assessed through wound healing experiments; Cell cycle and apoptosis were analyzed using flow cytometry; Protein expression of apoptosis-related proteins was examined using Western blot.Results:Compared with the control group, the absorbance of the protocatechuic acid groups (5 μM, 10 μM) decreased after 48 hours, and protocatechuic acid significantly inhibited cell proliferation ( P<0.05) . In the 5 μM protocatechuic acid treatment group, the proportion of cells in the G2/M phase increased to 25.26%, and in the 10 μM treatment group, the proportion of cells in the G2/M phase increased to 24.99%. Protocatechuic acid groups could arrest the cell cycle of the human ovarian cancer cell line A2780 at the G2/M phase. Protocatechuic acid groups could also promote the increase of early and late apoptosis rates of A2780 cells, leading to the upregulation of the expression levels of related apoptotic proteins CASPASE-3 and Bax, while the expression level of the anti-apoptotic protein Bcl2 was downregulated. Conclusions:Protocatechuic acid can inhibit proliferation and migration of A2780 ovarian cancer cells, arrest the cell cycle of A2780 cells, and promote apoptosis. The mechanism of action may be related to the upregulation of apoptosis-related proteins BAX and caspase3.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.

Objective To investigate the predictors of chronic pain after inguinal hernia surgery.Methods A total of 400 patients with inguinal hernia surgery in our hospital from August 2018 to May 2023 were selected as the study objects.Visual analog scoring(VSA)was used to evaluate postoperative acute pain within 24 h after surgery.The patients were divided into chronic pain group and non-chronic pain group according to whether chronic pain occurred after surgery.Thirty-seven patients with postoperative pain lasting more than 3 months were in the chronic pain group,and the remaining 363 patients were in the non-chronic pain group.Lasso-Logistic regression was used to analyze the predictors of acute and chronic pain after inguinal hernia surgery.Results Univariate analysis showed that there were significant differences in age,BMI,smoking history,preoperative groin pain,intraoperative nerve tension or injury,wound infection and postoperative acute pain between the chronic pain group and the non-chronic pain group(P＜0.05).The data were regularized by Lasso regression,and three representative risk factors of chronic postoperative pain,namely preoperative groin pain,intraoperative nerve pulling or injury,and postoperative acute pain,were selected.Multivariate Logistic regression analysis showed that:Preoperative groin pain(OR=2.548,95％CI1.150-5.647),intraoperative nerve tension OR injury(OR=4.435,95％CI2.084-9.436)and postoperative acute pain(OR=2.242,95％CI1.041-4.829)was the factor of chronic pain after operation(P＜0.05).Conclusion Preoperative groin pain,intraoperative nerve pulling or injury,and postoperative acute pain are the factors affecting chronic pain after inguinal hernia.Identifying high-risk groups and taking targeted measures are helpful to prevent and treat chronic pain after inguinal hernia.

Objective To investigate the mechanism of Wenhe Decoction in the treatment of febrile seizures through network pharmacology based on NLRP3/Caspase-1/GSDMD signaling pathway;To conduct experimental verification.Methods The active components and targets of Wenhe Decoction were retrieved and screened through TCMSP,BATMAN-TCM,PubChem databases and SwissADME platform.The disease targets of febrile seizures were found in GenCards,OMIM and DisGeNET databases.The intersection targets of Wenhe Decoction and the disease and the active components corresponding to the intersection targets were imported into Cytoscape 3.7.2 software to construct the Chinese materia medica-active components-targets network.The intersection targets were submitted to the STRING database to construct a protein-protein interaction network,and then the intersection targets were imported into the Metascape database for GO and KEGG pathway enrichment analysis.The febrile seizures rat model was established,and Wenhe Decoction of 4.05,8.1 and 16.2 g/kg were given respectively by gavage for 21 days.The rats were placed in batches in(45±0.5)℃constant temperature water bath to induce convulsive seizures,and the convulsive latency time and convulsive duration of rats were recorded.The behavioral differences of mice were observed.The morphology of hippocampal tissue were observed by HE and Nissl staining.The ROS content of hippocampal tissue was detected by DHE fluorescent probe technology.The serum ATP,GABA,Glu,Caspase-1,GSDMD,IL-1β and IL-18 contents were detected by ELISA,and the expression of NLRP3 inflammasome-related protein in hippocampal tissue was detected by Western blot.Results Network pharmacology analysis obtained 98 active components of Wenhe Decoction and 1 838 targets.162 targets were obtained by intersecting with disease targets,the core components for the treatment of febrile seizures were β-sitosterol,quercetin,luteolin,trans-squalene,sitosterol,saponin,etc.,and the core targets were EGFR,TNF,JUN,MTOR,etc.,and mainly through the regulation of inflammatory response,apoptosis,mitochondrial function and energy metabolism,mediating anti-inflammatory pathways such as PI3K-Akt signaling pathway and calcium signaling pathway to exert anticonvulsant effects.The experimental results showed that Wenhe Decoction could prolong the convulsive latency and shorten the duration of convulsions in febrile seizures model rats,decrease the level of convulsions,and the pathological damage of hippocampal tissue was improved and damaged neurons were repaired.The serum contents of ROS,Glu,Caspase-1,GSDMD,IL-1β and IL-18 were significantly reduced,and ATP and GABA contents significantly increased.The protein expressions of NLRP3,ASC,pro-Caspase-1,pro-IL-1β and pro-IL-18 in hippocampal tissue significantly decreased.Conclusion Wenhe Decoction may intervene in febrile seizures rats through NLRP3/Caspase-1/GSDMD signaling pathway,inhibit pyroptosis to reduce the occurrence of neuroinflammation,and then affect the balance of neurotransmitters Glu and GABA to play a role in anti-febrile seizures and prevent brain tissue damage.