Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

OBJECTIVE To systematically analyze the trends in the volume and value of out-licensing deals by Chinese biopharmaceutical companies over the past two decades， and to quantitatively identify factors associated with deal value， thereby providing an evidence base for policymakers and corporate managers. METHODS Based on the PharnexCloud database， information on out-licensing deals disclosed by Chinese biopharmaceutical companies between January 1， 2005 and December 31， 2025 was collected， and executed deals with disclosed specific financial terms were included for analysis. Descriptive statistical analyses of deal value， product characteristics and deal characteristics were performed using Stata SE 18.0； with the natural logarithm of deal value as the dependent variable， stepwise multiple regression models were constructed to examine the associations of product and deal characteristics with deal value. RESULTS A total of 210 out-licensing deals were included， with a cumulative deal value of approximately 214.151 billion dollars and a mean deal value of 1.020 billion dollars . The trading market expanded rapidly from 2020 onward， with the annual deal value reaching a record 95.687 billion dollars in 2025. Multiple regression analysis showed that the deal value of products at the drug discovery stage was significantly lower than that at the preclinical stage [regression coefficient （ β ） ＝－1.995， 95% confidence interval （CI）： －3.256 to －0.734， P ＜0.05 ] ； the deal value of oncology products was significantly higher than that of other therapeutic areas （ β ＝0.828， 95%CI： 0.224 to 1.431， P ＜0.05）； global licensing （ β ＝1.690， 95%CI： 1.107 to 2.273， P ＜0.05） and co-development arrangements （ β ＝0.849， 95%CI： 0.084 to 1.615， P ＜0.05） were significantly associated with higher deal value. CONCLUSIONS Out-licensing deals by Chinese biopharmaceutical companies have achieved significant growth in both volume and value over the past two decades. Oncology products， global licensing， and co-development arrangements are significantly and positively associated with higher deal value.

Renal lymphatic vessel density is clinically relevant in kidney disease but is still assessed by slow, subjective visual estimation. We evaluated a weakly supervised, attention-based multiple-instance learning framework for automated detection and quantification of renal lymphatic vessel density on D2-40-stained whole-slide images (WSIs). Methods: Two independent internal datasets from Tongji Hospital were collected, including 198 cases of chronic kidney disease (CKD) and 50 cases of hypertensive nephropathy (HTN). All biopsies were immunohistochemically stained for D2-40 and digitized as WSIs. Pathologists provided only slide-level labels (D2-40 high vs. D2-40 low). Tissue regions were automatically segmented, tiled into patches, and encoded using a pretrained convolutional neural network. Patch embeddings were then analyzed with a clustering-constrained attention multiple-instance learning (CLAM) model. Unlike conventional multiple-instance learning (MIL) methods that only weight instances, CLAM jointly performs attention-based instance selection and instance-level clustering to distinguish positive from negative evidence within each slide, yielding more discriminative slide-level features and interpretable attention maps. Performance was compared with a classic MIL model trained on the same features. Results: CLAM achieved area under the receiver operating characteristic curves of 0.942 and 0.858 on the CKD and HTN datasets, respectively, outperforming classic MIL (0.866 and 0.801). Attention maps highlighted lymphatic-rich regions consistent with renal pathologists’ assessments. Conclusions: This clustering-constrained, attention-based weakly supervised framework enables fully automated, reproducible quantification of renal lymphatic vessel density from WSIs, providing renal pathologists with rapid visual and numerical support for diagnosis and risk stratification in CKD and HTN.

ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats， which were randomized into a sham operation group （10 rats） and a modeling group （40 rats）. An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups （n=9 each）： The model group， the low-dose （7.87 g·kg^-1） Luoshi Neiyi prescription group， the high-dose （15.74 g·kg^-1） Luoshi Neiyi prescription group， and the dienogest （0.20 mg·kg^-1） group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin （HE） staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory factors including interleukin-1β （IL-1β） and prostaglandin E₂ （PGE₂） in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor A （VEGFA） in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated nuclear factor-κB （p-NF-κB）/NF-κB， MMP-9， and VEGFA in the eutopic endometrial tissue. In the cell experiments， the cell-counting kit-8 （CCK-8） assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum， and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum， resatorvid （TAK-242， a TLR4 inhibitor）， and lipopolysaccharides （LPS， a TLR4 agonist） were conducted， and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group， the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score （P<0.01）. Furthermore， HE staining revealed the model group exhibited a thickened eutopic epithelium， stromal cell disarrangement， and evident infiltration of inflammatory cells. In addition， the model group showed elevated serum levels of IL-1β and PGE₂ （P<0.05， P<0.01）， increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.01）， and up-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. Compared with the model group， all treatment groups exhibited a reduction in the ectopic lesion volume （P<0.01）. Furthermore， the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group （P<0.05， P<0.01）. The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE₂ levels， and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE₂ levels in EMs rats （P<0.05， P<0.01）. The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01） and down-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. The cell experiments showed that 5%， 10%， and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group， 5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA （P<0.01）. Compared with the control group， the LPS group showed increased expression of the above proteins （P<0.01）. Compared with the LPS group， the LPS+5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins （P<0.05， P<0.01）. ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive， invasive， and angiogenic biological processes in the ectopic endometrial tissue， thereby exerting its therapeutic effect on EMs.

Objective To observe clinical efficacy of Danggui Yinzi prescription combined with focused ultrasound in treatment of vulvar lichen sclerosus(VLS)with blood deficiency and dryness.Methods A total of 60 patients with blood deficiency and dryness VLS hospitalized in Gansu Provincial Hospital of Traditional Chinese Medicine from September 2023 to September 2024 were selected as study subjects,they were divided into control group(n=30)and treatment group(n=30)by random number table method.Control group was treated with focused ultrasound,and treatment group was treated with oral Danggui Yinzi prescription on the basis of control group.After 1 month of treatment,symptom scores(skin lesion area,color,etc.)and clinical efficacy of two groups were compared.Results After treatment,symptom scores of two groups were lower than those before treatment,and symptom scores of treatment group were lower than those of control group.Total effective rate of treatment group was higher than that of control group(P＜0.05).Conclusion Danggui Yinzi prescription combined with focused ultrasound is effective in treatment of VLS with blood deficiency and dryness,which can significantly reduce or eliminate itching symptoms and promote skin healing.

Objective To analyze the medication rules of traditional Chinese medicine compound patents for the prevention and treatment of urinary tract infection(UTI)through data mining technology.Methods The patents of traditional Chinese medicine compounds for the prevention and treatment of UTI in patent announcement module of China National Intellectual Property Administration website as data sources.The statistical analysis platforms of Excel 2021,IBM SPSS Modeler 18.0 and IBM SPSS Statistics 27.0 were used for frequency of use,medicinal properties,association rule analysis,and systematic clustering analysis and finally visualized by Cytoscape 3.7.2,RStudio.Results Through screening,a total of 179 compound patents met the inclusion criteria,involving 466 kinds of Chinese materia medica,and the top 5 high-frequency drugs were Pugongying,Huangbai,Gancao,Jinyinhua,Bianxu.The medicinal properties are mainly cold and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are liver,lung and kidney meridians.Common couplet medicines included Qumai-Bianxu,Gancao-Bianxu and the three herb drug combinations included Cheqianzi-Qumai-Bianxu,Gancao-Qumai-Bianxu.A total of 5 high-frequency combinations of traditional Chinese medicine were obtained by cluster analysis.Conclusion This study preliminarily reveals the compatibility and medication rules of traditional Chinese medicine in the treatment of UTI,which provides data support for the optimization of clinical syndrome differentiation and treatment system and the development of new prescriptions.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (ALAL) .Methods:A retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024. Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy, 8 received VAA+P regimen, and 5 received V+IA regimen. Patients with FLT3 mutation were treated with FLT3 inhibitor, and Ph + patients received an additional tyrosine kinase inhibitor. Overall survival (OS), disease-free survival (DFS), and adverse events were analyzed. Results:According to the World Health Organization 5th edition of the classification of hematolymphoid tumors, the immunophenotypes were T/myeloid mixed-phenotype acute leukemia (MPAL) ( n=4), B/myeloid MPAL ( n=7), and ALAL- not otherwise specified ( n=2). Of the seven patients with B/myeloid MPAL, four were Ph + and belonged to the group with specific gene abnormalities of ALAL. Three patients had FLT3 mutation (one with FLT3-TKD mutation and two with FLT3-ITD mutation). Prior to the second course of consolidation therapy, the efficacy of venetoclax induction therapy was evaluated, and a complete response rate of 100% was achieved in 13 patients. In the subsequent consolidation therapy phase, one patient discontinued treatment and was lost to follow-up; nine patients underwent allogeneic hematopoietic stem cell transplantation, four of whom died due to posttransplant complications and five achieved DFS. Of the three patients (≥70 years old) who received consolidation therapy as before, two achieved DFS and one died due to central nervous system leukemia. The median OS time was not reached in 13 patients; the 75th percentile survival time was 12.0 months, with a 12-month cumulative survival rate of 64.5%. The median DFS time was not reached in all patients; the 75th percentile DFS time was 8.2 months, with a 12-month cumulative DFS rate of 67.1%. All patients experienced grade 3 or 4 hematologic toxicity, including neutropenia and thrombocytopenia, during and after induction therapy. All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Conclusion:Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.

Objective:To explore the current implementation status and challenges of family doctor contract services (FDCS) from the perspective of contracted residents.Methods:This qualitative study used purposive sampling to select contracted residents from 11 primary healthcare institutions across five cities in China. Semi-structured interviews were conducted from March to December 2024, covering topics such as awareness of contracting, service experience, health needs, service continuity, and policy recommendations. Thematic framework analysis was applied to organize, code, and summarize the data.Results:A total of 25 contracted residents were interviewed (6 men, 19 women; 11 from central urban areas, 14 from suburban or rural towns; 8 with chronic diseases). Three main themes and ten sub-themes emerged: Theme Ⅰ: Pathways to improved service accessibility (optimized chronic disease management, more efficient referrals, and improved health education). Theme Ⅱ: Structural misalignment between supply and demand (limited specialty services despite patient needs, insufficient coverage and public awareness of home-based medical care, imbalanced human resources, and service disruption due to clinician turnover). Theme Ⅲ: Challenges in service awareness and communication mechanisms (information asymmetry and public misperception regarding FDCS, perverse incentives in administrative performance evaluation, and communication barriers in building patient-doctor trust).Conclusions:While FDCS has shown progress in chronic disease management, referral coordination, and health education, structural supply-demand gaps and communication challenges continue to hinder service quality. Improvements in resource allocation and service models are needed to support high-quality development.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.