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.

ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Objective To investigate the effect of erioside E on myocardial injury after myocardial infarction(MI)by regulating hypoxia-inducible factor-2α(HIF-2α)-mediated pyroptosis of cardiomyocytes and its possible mechanism.Methods Thirty rats were randomly divided into sham-operation group,MI group,and erioside E group,with 10 rats in each group.Cardiomyocytes H9C2 were cultured and divided into control group,hypoxia group,erioside E group and HIF-2α overexpression group.Masson staining was used to observe myocardial fibrosis and infarct size.The protein expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD were detected by Western blotting.RT-qPCR was used to detect the mRNA expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD.EdU kit was used to detect the proliferation of cardiomyocytes.The expressions of NLRP3,Caspase-1 and GSDMD proteins in cardiomyocytes were detected by immunofluorescence staining.Results Compared with the sham-operation group,the myocardial fibrosis level and infarct size were significantly increased in the MI group(P＜0.05),and the protein expressions of HIF-2α,pyroptosis-related proteins of NLRP3,Caspase-1 and GSDMD in myocardial tissue were increased(P＜0.05).Compared with the MI group,the level of myocardial fibrosis and infarct size were significantly decreased(P＜0.05),the protein expression of HIF-2α in myocardial tissue was increased,and the protein expressions of NLRP3,Caspase-1 and GSDMD were decreased in the erioside E group(P＜0.05).Compared with the control group,the hypoxia group had a significant reduction in the proliferation of cardiomyocytes and significant increase in the mRNA and protein expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD(P＜0.05).Compared with the hypoxia group,the proliferation ability of cardiomyocytes was significantly increased,and the expressions of HIF-2α,NLRP3,Caspase-1 and GSDMD mRNA in cardiomyocytes were decreased in the erioside E group(P＜0.05),while the protein expression of HIF-2α in cardiomyocytes was increased in the HIF-2αoverexpression group.The protein expressions of NLRP3,Caspase-1 and GSDMD were significantly decreased(P＜0.05).Conclusion Erioside E can improve myocardial injury by upregulating HIF-2α to inhibit myocardial pyroptosis.

Objective To explore the association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation(AF),and to evaluate the predictive value of SNORD55 for prognosis.Methods A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study.Their baseline information was collected,and the relative expression level of plasma SNORD55 was detected.Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients.The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients.The area under the receiver operating characteristic curve(AUC)was utilized to evaluate the discrimination,and the net reclassification index(NRI)and comprehensive discriminant improvement index(IDI)were calculated to evaluate the improvement of reclassification ability.Decision curve analysis(DCA)was applied to analyze the change in clinical net benefit.Results The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients.In predicting the outcomes of all-cause mortality and stroke,the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value[0.80(95％CI:0.67～0.93)vs 0.67(95％CI:0.53～0.81),P＜0.05].In predicting the outcome of all-cause death and stroke,combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI[54.3(95％CI:10.6～61.9)vs 31.9(95％CI:2.8～47.5),P＜0.05]and IDI[16.1(95％CI:2.4～27.0)vs 7.9(95％CI:0.5～14.8),P＜0.05].The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.Conclusion Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients,and has good predictive performance for all-cause mortality and stroke in the patients.

Objectives To explore the association of peripheral blood PIWI-interacting RNA,piR-hsa-2700592,with all-cause mortality and stroke outcomes in patients with atrial fibrillation(AF),and to determine whether piR-hsa-2700592 has the potential to be an AF biomarker.Methods A total of 127 patients with non-valvular AF were enrolled,and the relative expression level of plasma piR-hsa-2700592 was detected.Cox proportional hazard regression was used to analyze the correlation between the expression of piR-hsa-2700592 and all-cause death as well as stroke outcome in the patients.Then the molecule expression level was combined with CHA2DS2-VASc score and ABC stroke(or death)score to establish 2 new prediction models,the improvement of the predictive performance was compared and analyzed.Receiver operating characteristic(ROC)curve analysis(area under the curve,AUC),net reclassification index(NRI),and comprehensive discriminant improvement index(IDI)were used to evaluate the predictive performance,and decision curve analysis(DCA)was employed to assess the clinical benefit.Results Multivariate Cox regression analysis showed that the patients with higher expression level of piR-hsa-2700592 in peripheral blood had a higher risk of stroke(HR:2.203,95%CI:1.120～4.332;P=0.022).In the stroke outcome,combination of plasma piR-hsa-2700592 expression level with CHA2DS2-VASc score and ABC stroke score obtained an AUC of 0.70(95%CI:0.55～0.85,P＜0.001)and 0.84(95%CI:0.73～0.96,P=0.02),respectively.But,no significant association was observed between high plasma piR-hsa-2700592 level and all-cause mortality in the AF patients(HR:1.997;95%CI:0.884～4.509;P=0.096).Combination of plasma piR-hsa-2700592 level improved the discriminative capability than the single CHA2DS2-VASc score and ABC stroke score models,with an NRI and IDI value of 44.20%(95%CI:3.40～59.90,P＜0.001)and 8.20%(95%CI:0.60～15.40,P＜0.001),respectively for the new CHA2DS2-VASc score model,and an NRI and IDI value of 44.20%(95%CI:9.80～58.90,P＜0.001)and 10.40%(95%CI:0.70～21.40,P＜0.001),respectively for the new ABC stroke score model.The DCA curve showed that both new prediction models obtained better net clinical benefits.Conclusion High peripheral blood expression of piR-hsa-2700592 is an independent risk factor for stroke in the AF patients,and the indicator has a good predictive value for prognosis of the patients.piR-hsa-2700592 might be used as a potential biomarker in the diagnosis and prevention of cardiovascular diseases.

Objective:To investigate the association between blood pressure variability (BPV) and all-cause mortality and cardiovascular events in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and provide reference for clinical management in CAPD patients.Methods:This retrospective cohort study included patients who received CAPD at Guangdong Provincial People's Hospital between May 1, 2010, and July 31, 2023. Baseline and clinical data of the patients were collected. Coefficient of variation of systolic blood pressure (CVSBP) was used to assess BPV. The patients were divided into CVSBP T1, CVSBP T2 and CVSBP T3 groups based on CVSBP tertiles, and the differences among the three groups were compared. Diastolic blood pressure and mean arterial pressure were used to further assess BPV and sensitivity analysis was conducted. The primary endpoint was the composite outcome of all-cause mortality and cardiovascular events. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the association between CVSBP and the primary endpoint.Results:A total of 358 CAPD patients were included, with age of (43.6±13.3) years, and 197 males (55.0%). The proportion of males, proportion of smoking, baseline blood urea nitrogen, serum creatinine and serum albumin in CVSBP T2 (9.08%≤CVSBP<12.55%, n=120) group and CVSBP T3 (CVSBP≥12.55%, n=119) group were lower than those in CVSBP T1 group (CVSBP<9.08%, n=119), and baseline systolic blood pressure, residual kidney Kt/V and total Kt/V were higher than those in CVSBP T1 group, with statistically significant difference among the three groups (all P<0.05). During follow-up of 37(23, 76) months, 49 patients (13.7%) experienced the composite endpoint events, including 12 patients (3.4%) of all-cause deaths and 42 patients (11.7%) of cardiovascular events. Kaplan-Meier survival analysis showed that the incidence of composite endpoint events in CVSBP T3 group was higher than that in CVSBP T1 group and CVSBP T2 group, but the difference was not statistically significant (Log-rank χ2=3.795, P=0.150). Multivariate Cox regression analysis showed that, after adjusting for age, sex, diabetes, baseline systolic blood pressure, residual renal function, and serum albumin, as a continuous variable, CVSBP was not associated with the risk of composite outcome in CAPD patients ( HR=1.058, 95% CI 0.985?1.135, P=0.122); as a categorical variable, with CVSBP T1 group as reference, CVSBP T2 group and CVSBP T3 group were not associated with the risk of composite outcome ( HR=1.222, 95% CI 0.471?3.167, P=0.681; HR=1.827, 95% CI 0.737?4.530, P=0.193). The sensitivity analysis showed that increased variability of diastolic blood pressure ( HR=1.162, 95% CI 1.063?1.270, P=0.021) and increased variability of mean arterial pressure ( HR=1.114, 95% CI 1.030?1.204, P=0.007) were correlated with higher risk of composite outcome in CPAD patients. Conclusions:Systolic blood pressure variability during follow-up is not associated with risk of composite outcome of all-cause mortality and cardiovascular events in CAPD patients. Increased variability of diastolic blood pressure and increased variability of mean arterial pressure are associated with a higher risk of composite outcome in CPAD patients. Interventions to reduce BPV may be helpful to improve the long-term prognosis of CAPD patients.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Primary spontaneous pneumothorax (PSP) is an abnormal accumulation of gas in the pleural cavity without an underlying respiratory disease, excluding trauma or iatrogenic factors. The exact etiology and pathogenesis of PSP have not been clarified. Previous studies have confirmed that meteorological factors and environmental determinants such as atmospheric pollutant exposure can trigger the occurrence of pneumothorax, but no unified conclusion has been reached among different research results. This review summarizes the effects of meteorological factors and air pollutants on primary spontaneous pneumothorax.

Objective To study the need for blood compatibility evaluation of medical devices that come into indirect contact with blood in order to accurately evaluate the risk of their interaction with blood.Methods Seven medical devices with indirect contact with blood were selected as samples including extension tubes of central venous catheters,port bodies of implantable drug delivery devices,infusion sets,receiving lines of dialysis equipment,auxiliary lines of left ventricular assist devices,blood monitors and catheter holders,with high-density polyethylene as the negative control,glass beads as the positive control and blank whole blood or plasma for the blank control.Partial thromboplastin time(PTT)test,platelet count test and hematology test(white blood cell and red blood cell count)were performed by direct contact method and indirect contact method,respectively.In the direct contact method,whole blood or plasma was in direct contact with the sample;while in the indirect contact method,whole blood or plasma was not in direct contact with the extraction solution,with no direct contact with the sample.Results With the indirect contact method the ratios(expressed as a percentage)of the PTT,platelate,WBC and RBC counts of the samples,positive and negative controls to those of the blank control were all higher than those with the direct contact method,and the indirect contact method had the sensitivity lower than that of the direct contact method.Conclusion Medical devices indirectly contacting blood have low risks for causing coagulation and platelet and hematologic adverse reactions,which are suggested to be evaluated for hemolysis testing only in case of the history of safe clinical use.[Chinese Medical Equipment Journal,2025,46(8):44-49]