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.

ObjectiveTo observe the clinical efficacy of electroacupuncture in treatment of simple obesity patients and its effects on the metabolism-inflammation network. MethodsSeventy-two patients with simple obesity were randomly divided into a electroacupuncture group and a sham electroacupuncture group， with 36 patients in each group. In the electroacupuncture group， conventional acupuncture was applied at Zhongwan （CV 12）， bilateral Tianshu （ST 25）， bilateral Daheng （SP15）， Qihai （CV 6）， Guanyuan （CV 4）， bilateral Zusanli （ST 36） and Fenglong （ST 40）. The sham electroacupuncture group used placebo needle at same acupoints as the electroacupuncture group. Both groups were given sparse-dense waves with a frequency of 2/10 Hz， 30 minutes per session， 3 times a week， for a total of 8 weeks of treatment. The changes of human body parameters including body weight， body mass index （BMI）， waist circumference， and body fat percentage （BFP）， metabolic factors including serum fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， leptin， and ghrelin， and inflammatory factors including interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） were compared before and after treatment. Correlations between changes in leptin， ghrelin and inflammatory factors were further analyzed. ResultsWaist circumference was significantly reduced after treatment in both groups compared with baseline （P＜0.05）， and the post-treatment waist circumference was lower in the electroacupuncture group than in the sham electroacupuncture group （P＜0.05）； body weight， BMI and BFP decreased significantly after treatment compared to pretreatment levels in the electroacupuncture group （P＜0.05）. Serum leptin， IL-6 and TNF-α declined significantly after treatment in both groups versus baseline （P＜0.05）； the electroacupuncture group had lower post-treatment levels of leptin， IL-6 and TNF-α as well as larger pre-post changes than the sham group （P＜0.05）； ghrelin increased markedly after treatment in both groups （P＜0.05）， with higher post-treatment ghrelin and greater pre-post variation observed in the electroacupuncture group （P＜0.05）. In the electroacupuncture group， changes in ghrelin were negatively correlated with IL-6 and positively correlated with TNF-α （P＜0.01）； in the sham electroacupuncture group， ghrelin changes were negatively correlated with both IL-6 and TNF-α， whereas leptin changes were positively correlated with the two inflammatory markers （P＜0.01）. ConclusionElectroacupuncture can effectively improve clinical manifestations， as well as regulate serum metabolic and pro-inflammatory factors in patients with simple obesity， and discrepant correlation patterns of metabolism-inflammation are observed between the two groups.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

ObjectiveTo explore the potential mechanism of Xiaoqinglong Decoction （小青龙汤， XD） in the treatment of allergic rhinitis. MethodsForty-five rats were randomly assigned to a control group， a model group， a loratadine group， low-， medium- and high-dose XD groups， and low-， medium- and high-dose Mahuang Decoction and Cang'erzi Powder （麻黄汤合苍耳子散， MDCP） groups. Except for the control group， rats were administered with ovalbumin （OVA） and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14th-day injection， nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/（kg·d） of saline， whereas those in the loratadine group were administered with 0.9 mg/（kg·d） of loratadine. The low-， medium- and high-dose XD groups were administered XD at the dose of 2.7， 5.4， and 10.8 g/（kg·d）， respectively. The low-， medium- and high-dose MDCP groups were administered MDCP at the dose of 2.43， 4.86， and 9.72 g/（kg·d）， respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage， nasal symptom scores were recorded for all group of rats. The next day， serum levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR （RT-qPCR） and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin （TSLP） and OX40 ligand （OX40L） in the nasal mucosa. ResultsCompared to the control group， total nasal symptom score in the model group significantly increased （P＜0.01）. HE staining revealed disrupted and adhered cilia， thickened basement membranes， and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE， IL-4， and IL-13， as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa， were significantly elevated in the model group （P＜0.05 or P＜0.01）. Compared to the model group， the total nasal symptom scores in all drug intervention groups were significantly reduced； the serum total IgE levels in the loratadine group， the low- and medium-dose XD groups， and the low- and high-dose MDCP groups were significantly reduced； and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased （P＜0.05 or P＜0.01）. Nasal mucosal structure was improved. Except for the low-dose MDCP group， all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa （P＜0.01）. All doses of XD and the medium- and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L （P＜0.05）. The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA， and TSLP protein levels compared to the loratadine group （P＜0.05）. ConclusionXD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway， thereby attenuating Th2-mediated immune responses.

Objective: To present the plotting of trend analysis charts and the application of multi-rule trend analysis method for monitoring the quality of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells. Methods: Samples of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells were collected in accordance with relevant protocols and requirements. The results of blood quality testing were compiled. The trend line charts were plotted for the deviation rates of volume, hemoglobin (Hb) content, supernatant protein content, and leukocyte residual count. In addition, the trend line chart were plotted for hematocrit and post-storage hemolysis rate. Results: The trend analysis rules for the deviation rate of volume from the standard were: 1 categorized as out-of-control, (3 of 4) as warning, R as warning, 8 as alert, and 12 as alert. For Hb content deviation rate, the rules were: <0% categorized as out-of-control; <20% but ≥0% (for whole blood) or <10% but ≥0% (for washed red blood cells and leukocyte-depleted suspended red blood cells) as a warning. For supernatant protein content deviation rate, the rules were: ≥0.0% as out-of-control, and >-10% but <0.0% as a warning. For hematocrit, the rules were: 1 as out-of-control and (3 of 4) as warning. For leukocyte residual count deviation rate, the rules were: >0.0% as out-of-control, and >-10% but ≤0.0% as a warning. For post-storage hemolysis rate, the rule was: ≥0.8% out-of-control. Conclusion: The application of multi-rule trend analysis facilitates the timely identification of trend abnormalities and factors causing deviations in the collection and preparation processes of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells, thereby providing reliable numerical evidence for their correction and adjustment.

Thyroid diseases are common clinical endocrine disorders， and their pathogenesis is generally considered to be closely related to genetic predisposition factors， immune system disorders， hormone levels， etc. Xiaoyaosan is widely used in the treatment of various thyroid diseases with excellent effects. This study summarized the relevant literature on the treatment of thyroid diseases with modified Xiaoyaosan prescriptions and their active ingredients from aspects such as theoretical analysis， clinical research， and mechanism research. Theoretical analysis revealed that Xiaoyaosan could not only disperse stagnated liver qi but also replenish deficient spleen Qi， which was consistent with the etiology and pathogenesis of thyroid diseases. Clinical studies found that Xiaoyaosan and its modified prescriptions could be widely used in the treatment of multiple thyroid diseases， such as hyperthyroidism， Hashimoto's thyroiditis， and thyroid nodules. Both the use of modified Xiaoyaosan alone and in combination with medications such as methimazole， propylthiouracil， and euthyrox could effectively improve patients' clinical symptoms. In the mechanism research， this study discovered that the whole formula of Xiaoyaosan and its modified prescriptions could inhibit inflammatory reactions， regulate immune balance， and delay liver damage during the treatment of thyroid diseases. The research on Xiaoyaosan for treating thyroid diseases mainly focused on thyroid cancer， autoimmune thyroiditis， hyperthyroidism， and hypothyroidism. The mechanisms of action mainly involved promoting cell apoptosis， inhibiting cell proliferation and migration， arresting the cell cycle， and regulating thyroid hormone levels. In conclusion， this study systematically combs and summarizes the research status of Xiaoyaosan in treating thyroid diseases through literature retrieval， aiming to provide new perspectives and new ideas for the prevention and treatment of thyroid diseases with traditional Chinese medicine.

ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease （CHD） based on real-world clinical data， to establish a risk prediction model of integrated traditional Chinese and western medicine， in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD， who were divided into a training set and a validation set at a 7∶3 ratio. General information， traditional Chinese medicine （TCM）-related data， and laboratory test results were uniformly collected. After a one-year follow-up， patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination， calibration， and clinical decision curve analysis. ResultsA total of 682 patients were included， with 477 in the training set and 205 in the validation set， among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history ［OR = 6.93， 95% CI （1.58， 30.45）］， wiry pulse ［OR = 2.58， 95% CI （1.42， 4.72）］， weak pulse ［OR = 3.97， 95% CI （2.06， 7.67）］， teeth-marked tongue ［OR = 4.38， 95% CI （2.32， 8.27）］， blood stasis constitution ［OR = 2.17， 95% CI （1.06， 4.44）］， phlegm-stasis mutual syndrome ［OR = 3.64， 95% CI （1.87， 7.09）］， and elevated non-high-density lipoprotein cholesterol ［OR = 1.30， 95% CI （1.01， 1.69）］ as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability， with an area under the receiver operating characteristic curve （AUC） of 0.818 ［95% CI （0.781， 0.852）］ in the training set and 0.816 ［95% CI （0.779， 0.850）］ in the validation set. The Hosmer-Lemeshow test showed good calibration （χ² = 4.55， P = 0.80）， and the model's predictive ability was stable. When the threshold probability exceeded 5%， the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure， teeth-marked tongue， weak pulse， wiry pulse， phlegm-stasis mutual syndrome， blood stasis constitution， and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors， which showed good discrimination， calibration， and clinical utility， providing a scientific basis for predicting readmission events in patients with stable angina.

Objective To investigate the predictive value of preoperative ultrasound in combination with neutrophil-to-lymphocyte ratio(NLR),calcitonin(Ctn),and carcinoembryonic antigen(CEA)for cervical lymph node metastasis in patients with papillary thyroid carcinoma.Methods A total of 103 patients diagnosed with papillary thyroid carcinoma(PTC)who were admitted to the hospital between October 2021 and October 2024 were selected as the case group.Among them,34 patients with cervical lymph node metastasis confirmed by surgical and pathological examination were assigned to the metastatic group,and 69 patients without cervical lymph node metas-tasis were assigned to the non-metastatic group.Additionally,103 patients with benign thyroid nodules admitted during the same period were enrolled as the control group.Clinical data,ultrasonographic features,and serum levels of NLR,Ctn,and CEA were compared between the metastatic and non-metastatic groups.The predictive value of ultrasonographic features and the combined detection of NLR,Ctn,and CEA levels for cervical lymph node metastasis in PTC was evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared to the control group,the case group exhibited a higher proportion of patients with microcalcification and grade 3 blood flow,as well as elevated levels of NLR,Ctn,and CEA(P<0.05).Similarly,compared to the non-metastatic group,the metastatic group showed a higher proportion of patients with microcalcification and grade 3 blood flow,along with increased levels of NLR,Ctn,and CEA(P<0.05).The metastatic group tested positive,whereas the non-metastatic group tested negative.The area under the curve(AUC)for ultrasound features(micro-calcification,blood flow classification)combined with NLR,Ctn,and CEA levels in diagnosing cervical lymph node metastasis in papillary thyroid carcinoma was higher than that of individual indicators(P<0.05).Conclusions Preoperative ultrasound combined with the assessment of NLR,Ctn,and CEA levels demonstrates significant predictive value for cervical lymph node metastasis in papillary thyroid carcinoma.

Objective:To assess the sound localization ability of patients with unilateral sudden hearing loss during the early period of treatment, to explore its changing characteristics and to analyze influencing factors.Methods:A total of 22 patients with unilateral sudden sensorineural hearing loss, with onset within 3 days, who were hospitalized at Shandong Provincial ENT Hospital between January and April 2024, were collected in this study. The cohort included 13 males and 9 females, with a mean age of 36.5 years. Among them, 10 suffered in the right ear and 12 in the left ear. Additionally, 15 healthy individuals (8 males and 7 females, mean age 29.2 years) were selected as controls. Pure tone audiometry and sound localization tests were reviewed on the first day, third day, fifth day of admission; the third week after onset, and the pure tone average and the root-mean-square error(RMSE) were used as indicators, respectively. The improvement of the ability of sound localization and pure tone average were assessed by correlation analyses using SPSS, version 27.0, and multiple regression analysis was employed to explore effects that might influence sound localization ability.Results:The pure tone threshold and sound localization ability on the third week of onset were improved compared with those on the initial three instances(the first, third, and fifth days of admission). 9 of the 22 patients (40.91%, 9/22) presented normal sound localization ability whereas their hearing loss had not recurred yet. The Spearman correlation analysis revealed a significant positive correlation between the improvement of sound localization ability and hearing improvement ( r=0.57, P<0.001). Meanwhile, multiple regression analysis showed that hearing threshold was a significant factor for sound localization when there was audible frequency. Vice versa, at this circumstance, ages and vertigo were significant factors. Conclusions:For most of the patients with unilateral sudden hearing loss, ability of sound localization improves with the decrease of hearing threshold. Notably, some patients can restore normal levels of sound localization for white noise, even in the presence of hearing loss at certain frequencies, by relying on binaural acoustic cues provided by residual hearing.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.