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 explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo address the challenge of balancing efficiency and purity in isolating MSCs from rat thoracic aorta using traditional methods and to establish and validate an optimized isolation and culture system based on the dual-phase harvesting method. MethodsThoracic aortas were aseptically isolated from 3 to 4-week-old SD rats and minced. Three experimental groups were included： simple enzymatic digestion， pre-explant-enzymatic digestion sequential method， and the dual-phase harvesting method. Growth kinetic parameters， including time to initial cell migration， time to primary confluence， and cell yield， were systematically compared among the three groups. Passage‑4 cells were examined for surface marker expression （CD73， CD44， CD29， CD45， CD34， and CD11b/c） by flow cytometry. Their stemness was evaluated through osteogenic， adipogenic， and chondrogenic trilineage differentiation assays. ResultsThe time to primary confluence in the dual-phase harvesting method group （8.5 ± 1.0 ） d was significantly shorter than that of the simple enzymatic digestion group （11.2±1.2） d and the pre‑explant enzymatic digestion sequential group （12.8±1.5） d. Flow cytometric analysis revealed that the harvested cells consistently showed high expression of CD73 （87.2±1.5）%， CD44 （87.1±0.8）%， and CD29 （96.8±1.3）%， with low expression of CD45 （3.22±0.2）%， CD34 （2.46±0.5）%， and CD11b/c （2.53±2.1）%. Upon directed induction， the cells formed Alizarin Red‑positive calcium nodules， Oil Red O‑positive lipid droplets， and Alcian Blue-positive glycosaminoglycans， confirming complete trilineage differentiation potential. The cells could be stably expanded to passage 8 while maintaining a uniform elongated spindle-shaped morphology. ConclusionThe dual‑phase harvesting method established in this study is an efficient and stable optimized protocol for isolating MSCs from the rat thoracic aorta media. This approach synergistically enhances cell yield， purity， and stemness through its temporally designed two‑step process， thereby providing a high-quality in situ cell source for vascular biology research and regenerative medicine.

Objective: To evaluate the risk of donation-related adverse reactions, donation behavior, and contributions to the blood supply among donors aged 56-65 years following extension of the upper age limit for voluntary blood donation, and to provide real-world evidence for optimizing blood donation age policies in China. Methods: A multicenter retrospective cohort was established using blood donation databases from Hainan, Shenzhen, and Jiangxi. A total of 1 180 767 donors contributing 2 020 407 whole-blood and apheresis donations were included. Donations were classified by donor age at each donation into the 18-55-year and 56-65-year groups. Generalized estimating equation (GEE) models were used to compare the risks of overall, local, and systemic donation-related adverse reactions between the two age groups. Restricted cubic spline analysis was used to assess the continuous association between donor age and the risk of overall adverse reactions. Poisson GEE models were used to compare annual donation frequency, and donation participation and contributions to the blood supply among donors aged 56-65 years were evaluated. The study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (No.2025012) and registered with the Chinese Clinical Trial Registry (ChiCTR2500114960). Results: A total of 1 960 711 donations were included in the 18-55-year group and 59 696 in the 56-65-year group. The overall donation-related adverse reaction rates were 3.890‰and 0.704‰, respectively. Multivariable GEE analysis showed that, compared with donors aged 18-55 years, those aged 56-65 years had lower risks of overall adverse reactions (adjusted OR=0.294, 95%CI: 0.217-0.398, P<0.001) and systemic adverse reactions (adjusted OR=0.163, 95%CI: 0.101-0.263, P<0.001), whereas no statistically significant difference was observed in the risk of local adverse reactions (adjusted OR=1.337, 95%CI: 0.487-3.670, P=0.573). Donor age was nonlinearly associated with the risk of overall adverse reactions (P overall<0.001, P nonlinear<0.001), with the risk generally decreasing with increasing age between 18 and 65 years. The mean annual donation frequency was higher among donors aged 56-65 years than among those aged 18-55 years (1.63 vs 1.24 donations per year; adjusted IRR=1.34, 95%CI: 1.30-1.39, P<0.001). During the study period, donors aged 56-65 years contributed 2.95% of all donations; their whole-blood donations and whole-blood collection volume accounted for 2.36% and 2.37% of the corresponding totals, respectively. Conclusion: Under current health screening and standardized donor management, donors aged 56-65 years did not show an increased risk of short-term donation-related adverse reactions and demonstrated a higher annual donation frequency, together with a measurable contribution to the blood supply. These findings support appropriately extending the upper age limit for voluntary blood donation under strict health screening to broaden the donor pool and supplement the blood supply.

Objective To explore the effect of Xiongcan Yishen Formula on ferroptosis in testicular tissue of male rats with late-onset hypogonadism(LOH).Methods A total of 48 male Sprague-Dawley rats aged 6 months were randomly divided into model group,low-dose and high-dose Xiongcan Yishen Formula groups and propionate testosterone group,with 12 rats in each group.An additional 6 male Sprague-Dawley rats aged 8 weeks were set as the normal group.Except for the normal group,the rats were intraperitoneally injected with Cyclophosphamide at a dose of 20 mg/(kg·d)for 5 consecutive days to establish the LOH model,while the normal group received an equal volume of physiological saline for 5 days.The normal group and model group were given equal volumes of distilled water by gavage,while the low-dose and high-dose Xiongcan Yishen Formula groups were administered concentrated decoction at doses of 10.4 g and 41.6 g/kg/d respectively,and the propionate testosterone group received intramuscular injections of 5.21 mg/kg/d propionate testosterone,all for 28 consecutive days.ELISA was used to detect serum testosterone levels in rats,HE staining and transmission electron microscopy were used to observe the gross morphology of testicular tissue and the ultrastructure of Leydig cells,and RT-qPCR and Western blotting were used to detect the expression of ferroptosis-related genes and proteins in testicular tissue.Results The LOH model rats exhibited pathological changes such as atrophy of seminiferous tubules,structural disorder,and reduced spermatocytes in the lumen,as well as ultrastructural changes in Leydig cells including altered nuclear morphology,increased mitochondrial density,and reduced cristae.After intervention with Xiongcan Yishen Formula and propionate testosterone,the pathological changes in testis and the ultrastructure of Leydig cells were improved.Compared with the normal group,serum testosterone levels in the model group were significantly decreased(P＜0.05),the expression of ROS,ACSL4 mRNA and protein in testicular tissue was significantly increased,while the expression of FTH1,GPX4,and SLC7A11 mRNA and protein was significantly decreased(P＜0.05).Compared with the model group,ser-um testosterone levels in the low-dose and high-dose Xiongcan Yishen Formula groups and the propionate testosterone group were significantly increased(P＜0.05),and the expression of ROS,ACSL4 mRNA and protein was significantly decreased(P＜0.05);the high-dose Xiongcan Yishen Formula group showed significantly increased expression of FTH1,GPX4,and SLC7A11 mRNA and protein(P＜0.05).Conclusion Ferroptosis in testicular tissue is increased in LOH rats,and Xiongcan Yishen For-mula can elevate serum testosterone levels and improve pathological changes and ultrastructure in testicular tissue of LOH rats,possibly related to the inhibition of ferroptosis in testicular tissue of LOH rats.

Objective:To investigate the clinical effectiveness of Du Meridian moxibustion combined with brisk walking on negative symptoms, cognitive function, and social function in patients with stable schizophrenia, aiming to provide a feasible adjunctive treatment for clinical practice.Methods:A randomized controlled trial was conducted using convenience sampling to recruit 140 patients with stable schizophrenia hospitalized at the Affiliated Brain Hospital of Guangzhou Medical University from April 1, 2023, to March 31, 2024. Patients were randomly assigned to a control group, Du Meridian moxibustion group, brisk walking group, or combined group, with 35 patients in each group. The control group received standard care. On this basis, the Du Meridian moxibustion group received moxibustion on the Du Meridian, the brisk walking group participated in slow walking exercises, and the combined group received both interventions for 12 weeks. Assessments were conducted at baseline, at 6 and 12 weeks during the intervention, and at 12 weeks post-intervention using the Scale for the Assessment of Negative Symptoms, Mini-Mental State Examination, and Social Functioning Scale for Inpatient Psychiatric Patients.Results:A total of 134 patients completed the study: control group ( n = 34), Du Meridian moxibustion group ( n = 34), brisk walking group ( n = 35), and combined group ( n = 31). The combined group demonstrated significantly lower SANS scores at the 12th week of intervention (49.71 ± 4.66) and at 12 weeks post-intervention (53.45 ± 5.34) compared to the Du Meridian moxibustion group (54.91 ± 4.79) and (59.56 ± 5.84), the brisk walking group (56.69 ± 5.59) and (58.51 ± 5.42), control group (65.71 ± 4.95) and (66.21 ± 4.33), with statistically significant differences ( t values were 3.81-13.37, all P<0.05). Regarding cognitive function, the MMSE scores in the combined group at the 12th week of intervention (28.23 ± 1.28) and at 12 weeks post-intervention (27.35 ± 1.76) were higher than those in the Du Meridian moxibustion group (26.79 ± 1.85) and (25.59 ± 2.27) and the brisk walking group (25.88 ± 2.23) and (25.43 ± 1.84), control group (23.65 ± 2.17) and (22.32 ± 2.14), with statistically significant differences ( t values were - 10.28 to - 3.48, all P<0.001). For social function, the SSPI scores in the combined group at the 12th week of intervention (35.71 ± 3.63) and at 12 weeks post-intervention (32.58 ± 3.71) were also significantly higher than those in the Du Meridian moxibustion group (32.21 ± 3.91) and (28.47 ± 3.70) and the brisk walking group (31.83 ± 3.54) and (30.31 ± 3.59), control group (24.53 ± 4.12) and (24.15 ± 3.50) with statistically significant differences ( t values were - 11.56 to - 2.52, all P<0.05). Conclusions:The combination of Du Meridian moxibustion and brisk walking is an effective adjunctive intervention for patients with stable schizophrenia, as it significantly reduces negative symptoms, enhances cognitive function, and improves social functioning.

Objective:To construct a quality evaluation index system for perianal infection care in patients with hematologic neoplasms, aiming to establish a standardized approach for care.Methods:A quality evaluation index system for perianal infection management in patients with hematologic neoplasms was developed from January to June 2023 using Donabedian′s "Structure- Process- Outcome" approach, based on evidence- based literature study and expert conference discussions. An index system for evaluating the quality of perianal infection care in patients with hematologic neoplasms was established through expert consultation, and the weights for each indicator were derived using the analytic hierarchy process.Results:Two rounds of expert consultations were conducted, involving 27 experts aged 30 to 53 (38.85 ± 6.13) years, in which of them there were 1 male and 26 females. The positive coefficients of the experts in the two rounds of consultations were 100.00% (27/27) and 96.30% (26/27), respectively. The expert authority coefficients were 0.874 and 0.881, respectively, and the Kendall coordination coefficients were 0.234 and 0.219 (both P<0.05). The quality evaluation index system for perianal infection management in patients with hematologic neoplasms consisted of 3 main indicators (structural quality, process quality, outcome quality), 12 secondary indicators, and 48 tertiary indicators. Conclusions:The process of developing the quality assessment criteria for perianal infection care in patients with hematologic neoplasms is systematic and yields dependable results. The criteria cover a wide range of aspects and are specific, offering a valuable framework for assessing the quality of perianal infection care in patients with hematologic neoplasms.

Inflammatory breast cancer(IBC)is a rare but highly aggressive subtype of breast cancer characterized by rapid clinical progression and poor prognosis.Although it accounts for only 2%-4%of all breast cancer cases,it is responsible for 8%-10%of breast cancer-related mortality.The etiology of IBC is multifactorial,involving genetic,hormonal,environmental,and socioeconomic factors.Pathologically,IBC is marked by the presence of dermal lymphatic tumor emboli,and molecular subtypes are predominantly HER2-positive and triple-negative,indicating high tumor invasiveness.Diagnosis relies on characteristic clinical manifestations and histopathological confirmation,while imaging techniques such as MRI and PET/CT play important roles in evaluating disease extent and metastasis.Given that IBC is often diagnosed at a locally advanced or metastatic stage,there is currently no specific treatment protocol.Instead,management generally follows the treatment paradigm of non-IBC,emphasizing systemic therapy within a multidisciplinary framework.HER2-positive IBC benefits from chemotherapy combined with dual-targeted anti-HER2 therapy;triple-negative IBC may respond to immune checkpoint inhibitors;and CDK4/6 inhibitors show potential efficacy in hormone receptor-positive subtypes.Despite advancements,the prognosis remains poor,with a high risk of early recurrence and distant metastasis.Prognostic factors include lymph node involvement,molecular subtype,and response to neoadjuvant therapy.As research into the tumor microenvironment and molecular mechanisms deepens,targeted and individualized therapies hold promise for improving outcomes.This review summarizes the epidemiology,pathology,diagnostic criteria,treatment strategies,and prognostic factors of IBC,aiming to inform clinical practice and future research.

Venous thrombosis is one of the common and serious complications after pancreas transplantation. The organ transplantation center of Shanxi Bethune hospital innovatively improved the previous surgical method of ligating the splenic artery and splenic vein to perform end-to-end anastomosis between the splenic artery and splenic vein in the tail of the pancreas and retain the effective diameter of the splenic artery of about 2 mm to increase the blood flow of splenic vein to prevent thrombosis. The center has successfully completed 2 cases, and the operation effect is good. Postoperative monitoring of abdominal vascular CT angiography showed that the splenic vein reflux was unobstructed. This operation can effectively increase the blood flow of splenic vein and reduce the risk of thrombosis.