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.

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.

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.

Objective:To evaluate the effect of an electronic balance aid in balance rehabilitation training for patients with acute peripheral vestibular injury by comparing the outcomes of medication-only treatment and medication combined with vestibular rehabilitation using an electronic balance aid.Methods:This was a randomized controlled trial. The study subjects included 98 patients (40 males and 58 females, aged 25-69 years) diagnosed with idiopathic sudden sensorineural hearing loss (ISSNHL) with vertigo or vestibular neuritis, who were treated in the Department of Otorhinolaryngology-Head and Neck Surgery of Tianjin First Central Hospital from November 2022 to November 2023. All patients were randomly divided into the experimental group and the control group at a 1∶1 ratio using the sealed envelope method. Control group (conventional drug treatment): Patients received medication treatment for 2 weeks, including betahistine mesilate tablets, vitamin B1 tablets, methylcobalamin tablets, ginkgo biloba tablets, diphenhydramine hydrochloride injection (within 3 days of onset), metoclopramide hydrochloride injection, and glucocorticoids. Experimental group (conventional drug treatment+device training): On the basis of the same medication treatment as the control group, patients received vestibular rehabilitation training using an electronic balance aid (20 minutes per session, once a day,≥5 days per week, for a total of 2 weeks). SPSS software was used to compare the total scores of the Dizziness Handicap Inventory (DHI), the total scores of the Sensory Organization Test (SOT), and sensory analysis indicators between the two groups before and after treatment.Results:After treatment, vertigo symptoms significantly improved in both groups. DHI: The total DHI score in the control group decreased from 77.9±1.8 before treatment to 20.2±2.3 after treatment ( P<0.001). In the experimental group, the total DHI score decreased from 73.5±2.1 before treatment to 8.6±0.9 after treatment ( P<0.001). The difference in total DHI scores between the two groups after treatment was statistically significant, with the experimental group showing a lower score ( t=-4.616, P<0.001). The improvement in DHI scores was also more pronounced in the experimental group compared to the control group ( t=2.004, P=0.048). SOT: The total SOT score in the control group increased from 52.90±0.95 before treatment to 73.3±1.1 after treatment ( P<0.001). In the experimental group, the total SOT score increased from 54.9±0.8 before treatment to 83.5±0.9 after treatment ( P<0.001). The difference in total SOT scores between the two groups after treatment was statistically significant, with the experimental group showing a higher score ( t=7.104, P<0.001). The improvement in SOT scores was also more pronounced in the experimental group compared to the control group ( t=6.532, P<0.001). Sensory Analysis Indicators Proprioception (SOM): In the experimental group, the proprioception score significantly increased after treatment compared with before treatment ( t=-2.338, P=0.029), while, there was no statistically significant difference in the proprioception score of the control group before and after treatment ( P=0.537). Before treatment, there were no statistically significant differences in visual, vestibular, or visual dependence scores between the two groups (all P>0.05). After treatment, the visual, vestibular, and visual dependence scores of both groups significantly increased compared with those before treatment (all P<0.05); moreover, the post-treatment visual, vestibular, and visual dependence scores of the experimental group were significantly higher than those of the control group (all P<0.05). Conclusion:Compared with medication-only treatment, the combination of an electronic balance aid and medication for the treatment and rehabilitation training of patients with acute peripheral vestibular injury can significantly improve the therapeutic effect in the short term.

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Objective:To analyze the epidemiological and clinical characteristics of Mycoplasma pneumoniae ( Mp) infection among hospitalized children with acute respiratory tract infections (ARTIs) in a single center in Beijing and provide reference for the prevention and treatment of Mp infection. Methods:Nasopharyngeal aspirate (NPA) samples of hospitalized children with ARTIs were collected from Beijing Friendship Hospital during two periods: from April 2018 to March 2019 and from September 2020 to August 2022. qPCR was used to detect Mp nucleic acids, and for Mp-positive samples, the mixed infections with 15 common respiratory viruses were detected. Statistical analysis was conducted using Chi-square test, Fisher′s exact test, and independent samples t-test. Results:From April 2018 to March 2019, 1 572 NPA samples were collected, with 104 positive for Mp (6.62%). From September 2020 to August 2022, 622 samples were collected, with 22 Mp-positive samples (3.54%). There was statistically significant difference in the positive rates between the two time periods ( P<0.05). From April 2018 to March 2019, the positive rate of Mp was higher in children aged ≥5 years than in those <5 years [13.03% (46/353) vs 4.76% (58/1 219), P<0.05]; the positive rates in summer (9.54%, 35/367) and autumn (7.93%, 33/416) were higher than those in spring (3.03%, 11/363) and winter (5.87%, 25/426), with statistically significant differences ( P<0.05); co-infections with other respiratory viruses were detected in 42 out of the 104 Mp-positive cases (40.38%), primarily with human rhinovirus (35.71%, 15/42) or human coronavirus NL63 (19.05%, 8/42). From September 2020 to August 2022, Mp infections mainly occurred in children aged ≥5 years [72.73% (16/22)], and co-infections with other respiratory viruses were detected in four cases (18.18%, 4/22). The Mp-infected children were mainly diagnosed with pneumonia, and there was no significant difference in clinical symptoms between Mp-infected patients with or without viral coinfection. Conclusions:The positive rate of Mp among hospitalized children with ARTIs in Beijing from September 2020 to August 2022 is significantly lower than that observed from April 2018 to March 2019. Mp is an important cause of ARTIs in children, especially in patients aged ≥5 years. Mp infection is often accompanied by viral co-infections, with high incidence in summer and autumn.

The study was a prospective observational study. A total of 24 patients who underwent maintenance hemodialysis (MHD) at Haidian Hospital in Beijing from May 2024 to June 2024 were included as the study subjects. The safety and efficacy of a new single-needle dialysis in MHD patients were evaluated. The reasons for using single-needle dialysis included waiting for the maturity of internal fistula(7 cases, 29.17%), autogenous arteriovenous fistula thrombosis occurred (6 cases, 25.00%), puncture difficulty occurred (7 cases, 29.17%), and pain sensitivity or elderly (4 cases, 16.67%). The results showed that the average blood flow was (155.65±5.90) ml/min, total blood volume was (35.92±2.65) L during single-needle dialysis. One patient had slight puncture leakage, and the puncture success rate was 95.83%. Relevant indicators of dialysis adequacy showed that the average urea clearance (Kt/V) was 0.90±0.42, urea reduction ratio was 58.31%±7.93%, and online real-time Kt/V monitoring average value was 0.98±0.55. The results suggest that the application of the new improved single-needle dialysis mode in MHD patients is safe and effective.

Objective:To investigate the prognostic value of aldosterone synthase (CYP11B2) immunohistochemical expression in adrenal specimens for surgical outcomes of primary aldosteronism (PA).Methods:The clinical data of 99 patients who underwent total unilateral adrenalectomy from June 2022 to January 2023 at Beijing Anzhen Hospital was retrospectively analysed. The clinical data of 99 patients who underwent unilateral total adrenalectomy at Beijing Anzhen Hospital from June 2022 to January 2023 were retrospectively analyzed.There were 59 patients in the PA group, age (53.02±10.56) years, body mass index (BMI) (26.28±4.33) kg/m 2, preoperative aldosterone 29.0(15.9, 61.5)ng/dl, plasma renin 1.3(0.6, 2.8)μIU/ml, aldosterone renin ratio (ARR) 19.3(9.1, 59.2) μg/μIU, preoperative potassium (3.60±0.69) mmol/L, and systolic blood pressure (156.54±21.39) mmHg (1 mmHg=0.133 kPa).There were 40 cases in the nonfunctioning adenoma (NFA) group, age (57.23±9.39) years, BMI (27.07±3.46) kg/m 2, preoperative aldosterone 9.0(7.2, 14.1) ng/dl, plasma renin 18.0(5.2, 47.6)μIU/ml, ARR 0.6(0.2, 1.4) μg/μIU, preoperative potassium (4.17±0.41) mmol/L, and systolic blood pressure (157.97±26.87) mmHg. The differences between the two groups were statistically significant for potassium ( P<0.01), aldosterone ( P=0.012), renin ( P<0.01), and ARR ( P<0.01).Surgical outcomes were assessed using the Consensus on the Outcome of Surgery for Primary Aldosteronism (PASO) (complete/partial/no success for clinical and biochemical outcomes). CYP11B2 expression was evaluated by immunohistochemistry using the 2022 World Health Organization's histopathology of primary aldosteronism (HISTALDO) criteria. The correlation between the expression of CYP11B2 and surgical outcomes was assessed. Results:The mean follow-up of 99 patients was (11.73±4.92) months. Of these, 36 out of 59 PA patients had positive CYP11B2 expression in their adrenal specimens, while 23 were negative; all 40 NFA patients were negative for CYP11B2. Among the 36 CYP11B2-positive PA patients, there were 19 cases of aldosterone-producing adenomas, 3 aldosterone-producing nodules, 4 aldosterone-producing micronodules, 8 multiple aldosterone-producing micronodules, and 2 aldosterone-producing diffuse hyperplasia. 36 cases of CYP11B2-positive PA patients had complete clinical success in 15 cases, partial success in 20 cases, and no success in 1 case, and complete biochemical success in 24 cases, partial success in 11 cases, and no success in 1 case; 23 CYP11B2-negative PA patients had complete clinical success in 4 cases, partial success in 15 cases, and no success in 4 cases, and complete biochemical success in 6 cases, partial success in 15 cases, and no success in 2 cases. Adrenal specimens from CYP11B2-positive PA patients had significantly better clinical ( P=0.038) and biochemical ( P=0.008) success rates than CYP11B2-negative PA patients. Patients with aldosterone-producing adenomas had complete clinical success in 8 cases, partial success in 11 cases, and no success in 0 cases, and biochemical success was completely achieved in 16 cases, partially achieved in 2 cases, and not successful in 1 case. They also had significantly higher clinical ( P=0.028) and biochemical ( P<0.01) success rates compared to CYP11B2-negative PA patients. Conclusions:Patients with PA who had immunohistochemical staining for CYP11B2 positivity and high expression in adrenal specimens had a better postoperative clinical and biochemical prognosis. Patients with aldosterone-producing adenomas had the greatest postoperative outcome of all pathological subtypes of PA.

Objective To evaluate the accuracy of using HIrisPlex-S system for eye color,hair color,and skin color prediction in forensic DNA phenotyping(FDP).Methods A total of 49 unrelated individuals were enrolled.First,based on the collected facial photographs and questionnaire responses,the actual phenotypic traits,including eye color,hair color,and skin color,of the participants were manually assessed and categorized.Subsequently,peripheral blood samples were collected from the participants,and DNA was extracted.Genotyping of the HIrisPlex-S system was performed using the SNaPshot method combined with capillary electrophoresis.Single nucleotide polymorphism(SNP)sites were analyzed using the online HIrisPlex-S prediction platform(https://HIrisPlex.erasmusmc.nl/)to predict the aforementioned phenotypic traits.Two different methods were used to interpret the prediction results.In Method 1,the phenotypic trait with the highest probability value were directly selected as the predicted phenotype.In Method 2,the prediction guidelines proposed by Manfred Kayser's team was applied.The sensitivity and specificity of the predictions were calculated by comparing the prediction results with the manually interpreted actual phenotypic data,and the differences between the two interpretation methods in these performance metrics were compared.Additionally,two real case samples were included for phenotypic inference analysis to validate the system's effectiveness in practical applications.Results Among the participants,approximately 55%had"brown"eyes,while"intermediate"eye color was less common;approximately 45%had"black"hair;and approximately 39%had"pale"skin.After optimizing the concentration of single base extension(SBE)primers,the peak balance of most SNP loci in the HIrisPlex-S system improved,though inter-laboratory reproducibility remained suboptimal.In eye color prediction,the sensitivity of Method 1(0.875 0,0.000 0,and 1.000 0)was slightly higher than that of Method 2(0.812 5,0.000 0,and 0.925 9),while the specificity of Method 1(0.848 5,1.000 0,and 0.818 2)was slightly lower than that of Method 2(0.909 1,1.000 0,and 0.909 1).For hair color prediction,the two methods showed identical sensitivity(0.772 7,0.615 4,and 0.857 1),but Method 2 showed slightly better specificity(1.000 0,0.944 4,and 0.714 2)than Method 1(1.000 0,0.916 7,and 0.742 9).In skin color prediction,both the sensitivity(0.000 0,0.789 5,1.000 0,0.333 3,and 0.875 0)and specificity(1.000 0,0.966 7,0.833 3,0.976 7,and 0.878 0)of Method 2 were slightly higher than those of Method 1(sensitivity:0.000 0,0.578 9,0.923 1,0.166 7,and 0.750 0;specificity:1.000 0,0.966 7,0.694 4,0.953 5,and 0.878 0).However,overall,there was no statistically significant difference in sensitivity or specificity between the two methods(P>0.05).Additionally,the phenotypic predictions for the two real case samples were consistent with genetic ancestry analysis.Conclusion The HIrisPlex-S system can be used to predict the eye and hair colors in population samples,but its accuracy in skin color prediction needs further improvement.

ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.