ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

This paper has constructed a traditional Chinese medicine （TCM） specialized disease dataset platform for mixed hemorrhoids based on a multimodal large model， and the preliminary application has been validated. The platform uses StarRocks to establish a four-level data warehouse system， enabling the aggregation， cleaning， and standardization of multi-source heterogeneous data. Using DeepSeek-R1-Distill-Qwen-7B as the base model， domain fine-tuning is performed through low-rank adaptation （LoRA） technology. Combined with LLaMA-3.3 natural language processing and reasoning chain techniques， the platform enables intelligent parsing and structured extraction of unstructured TCM medical records. It accurately identifies six major categories and 28 subcategories of entities， including symptoms and syndromes， with a fine-tuned model F1 score of 93.8%. The platform has established a high-quality specialized disease dataset containing more than 50,000 medical records and has been applied in a real-world study involving 17,831 patients， preliminarily verifying the efficacy of TCM heritage surgery.

Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC WP0 potently degraded PD-L1 and induced T-cell-mediated tumor killing against HepG2 cells, highlighting the potential therapeutic applications. The development of GLTAC technology expands the scope of TPD strategies and opens new avenues for discovering novel therapeutic modalities against challenging protein targets.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective This study evaluates the research landscape,trends,and emerging hotspots in parathyroid ultrasound over the past 20 years using bibliometric methods and visualization tools,while providing insights into future research directions.Methods A comprehensive search was conducted in PubMed and Web of Science Core Collection(WOSCC)databases for parathyroid ultrasound stud-ies published between 1 January,2004 and 5 September,2024.A total of 1609 articles were included.Bibliometric analyses were per-formed using CiteSpace and VOSviewer to identify publication trends,key contributors,and research hotspots of parathyroid ultrasound.Results Annual publications in parathyroid ultrasound steadily increased,with China and the United States leading in research output.The most prolific author came from China,and the World Journal of Surgery was the leading journal in this field.Recent keywords,inclu-ding tertiary hyperparathyroidism,parathyroidectomy,and thermal ablation.Future research is expected to emphasize interdisciplinary col-laboration and the integration of emerging imaging technologies.Conclusion This study provides a comprehensive overview of research progress in parathyroid ultrasound,indicate emerging research frontiers and future trends.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Objective:To analyze the epidemiological characteristics and influencing factors of single-cigarette use and dual cigarette-cigar use in China.Methods:This study was a cross-sectional study that selected 85 638 urban and rural residents who met the inclusion criteria from the 2018 China Health Literacy Survey as research subjects. An analysis was conducted on 21 849 users of cigarettes and cigars among them. Due to the small number of individuals who exclusively used cigars (247 cases), the research subjects were divided into two categories: exclusive cigarette users and dual users of cigarettes and cigars. The groups were categorized by age (18-34 years, 35-54 years, ≥55 years), gender (male, female), education level (primary school and below, junior high school and high school, university and above) and annual household income (<20 000 yuan, 20 000-<80 000 yuan, ≥80 000 yuan) to compare the tobacco usage rate and conduct subgroup analyses for each subgroup. Multivariate logistic regression analysis was employed, incorporating general demographic characteristic information to explore the influencing factors of exclusive cigarette use and dual use of cigarettes and cigars, respectively.Results:The rate of exclusive cigarette use in our country was 24.3%, while the dual use rate of cigarettes and cigars was 0.9%. The exclusive cigarette use rate and the dual use rate of cigarettes and cigars among males were significantly higher than those among females (48.25% vs 2.48%, and 1.84% vs 0.06%) (both P<0.001). For males, the high-risk factors for exclusive cigarette use included living in urban areas ( OR: 1.37, 95% CI: 1.23-1.54), being Han ethnicity ( OR: 1.73, 95% CI: 1.51-1.98), and having an annual household income ≥20 000 yuan ( OR: 1.54, 95% CI: 1.38-1.82) while having a junior high school education or higher was a protective factor ( OR: 0.68, 95% CI: 0.52-0.90). Age≥35 years ( OR: 3.36, 95% CI: 2.62-4.32) and having a junior high school education or higher ( OR: 1.30, 95% CI: 1.02-1.67) were risk factors for dual use of cigarettes and cigars in males. Among females, living in urban areas ( OR: 1.53, 95% CI: 1.19-1.97) and being Han ethnicity ( OR: 5.96, 95% CI: 4.47-7.96) were risk factors for exclusive cigarette use, while having a university education or higher was a protective factor ( OR: 0.28, 95% CI: 0.18-0.42). However, for female dual use of cigarettes and cigars, no significant effects were observed for any demographic characteristics. Conclusions:The use rate of cigarettes alone in China is significantly higher than that of cigarette-cigar dual use, and the rates of cigarette use alone and cigarette-cigar dual use in men are significantly higher than those in women. Tobacco use is being affected by sociodemographic factors, among which place of residence, ethnicity and education level are the main influencing factors of cigarette use alone, and gender, age and education level are the main influencing factors of cigarette-cigar dual use.

Objective:To assess the value of artificial intelligence（AI）assisted system in the diagnosis of malignancy in follicular thyroid tumours，and to compare with the diagnostic results of doctors with different levels of experience.Methods:A total of 101 nodules were retrospectively collected from 86 patients with follicular thyroid tumours who underwent surgical treatment at Peking Union Medical College Hospital，Chinese Academy of Medical Sciences，Peking Union Medical College from May 2016 to January 2018.The nodules were classified into risk group（29 patients，34 nodules，including 15 follicular carcinomas and 19 follicular tumours of indeterminable malignant potential）and benign group（59 atients，67 nodules，including 15 follicular adenomas and 52 nodular goitre adenomatoid hyperplasia）. The sensitivities，specificities and accuracies of the AI system，two doctors of different seniorities（one junior A and one senior B），and guidelines of thyroid ultrasound malignancy risk stratification［including the 2015 American Thyroid Guidelines（ATA），the 2017 American College of Radiology Thyroid Imaging Reporting and Data System（ACR TI-RADS），the 2020 Chinese Society of Ultrasound，Thyroid Imaging Reporting and Data System（C-TIRADS）］（classified by a senior doctor C）for diagnosing follicular tumours in the risk group and follicular carcinomas were calculated and compared.Results:The AI system showed a sensitivity of 46.7%，specificity of 89.6% and accuracy of 81.7% for diagnosing follicular carcinoma；and a sensitivity of 32.4%，specificity of 89.6% and accuracy of 70.3% for diagnosing follicular neoplasms（risk group）. Compared with junior doctor A，the specificity of AI system in diagnosing follicular cancer and follicular neoplasms（risk group）was higher（89.6% vs. 83.6%， P=0.020；89.6% vs. 73.1%， P=0.020），and the differences of sensitivity were not significant（46.7% vs. 32.4%， P=0.181；32.4% vs. 11.8%， P=0.073）. The difference of sensitivity and specificity were not statistically significant between the AI system and senior doctor B（all P＞0.05）.The differences in area under the curve for diagnosis of follicular carcinoma and follicular tumour（risk group）were not statistically significant between the AI system compared to junior doctor A，senior doctor B，the C-TIRADS，ATA guideline，and ACR TI-RADS（all P＞0.05）. Conclusions:Ultrasound-based AI-assisted diagnostic system is similarly efficient in diagnosing follicular thyroid tumours as experienced doctors，and the AI system diagnostic specificity is superior to that of junior doctors.

Objective:To evaluate the application value of the Supply-Processing-Distribution(SPD)supply chain mode in the refined management for medical consumables in hospital on the basis of SPD supply chain mode.Methods:An integrated efficiency index system was constructed based on SPD,and the Analytic Hierarchy Process(AHP)and Entropy Method were used to determine index weights by combined weighting.Medical consumables were classified and managed according to the index weight values.A total of 63,461 types of medical consumables(included low-value medical consumables and high-value medical consumables)that was used in clinical practice at Beijing Anzhen Hospital,Capital Medical University from January to June 2021 and January to June 2023 were selected.In them,the 54,632 types of medical consumables that were used between January and June 2021 were managed by adopting conventional supply chain mode,while 56,471 types of medical consumables that were used(included 47,642 types of medical consumables that were managed by conventional supply chain made at the first stage,and 8,829 types of new medical consumables)between January and June 2023 were managed by adopting the SPD supply chain mode.The inventory amount,inventory quantity,loss rate,and return or change rate of medical consumables of the two management modes were compared.A self-designed satisfaction questionnaire was used to evaluate the satisfaction of medical staffs,who used these medical consumables,for the two kinds of management modes.Results:The inventory amount of low-value medical consumables that were managed by the SPD supply chain mode was(1,424.09±75.68)million CNY,which was lower than(2,290.79±215.93)million CNY of adopting conventional supply chain mode,with a statistically significant difference(t=8.85,P<0.05).The inventory amount of high-value medical consumables that were managed by the SPD supply chain mode was 0,which was lower than(7,692.32±360.53)million CNY of adopting conventional supply chain mode,with a statistically significant difference(Z=-2.201,P<0.05).The inventory quantities of both low-value and high-value medical consumables of adopting SPD supply chain mode were significantly lower than those of adopting conventional supply chain mode,with statistically significant differences(t=10.443,11.225,P<0.05).The average loss rates of both low-value and high-value medical consumables of adopting SPD supply chain mode were significantly lower than those of adopting conventional supply chain mode,with statistically significant differences(Z=-2.207,-2.201,P<0.05).The average return or change rates of both low-value and high-value medical consumables of adopting SPD supply chain mode were significantly lower than those of adopting conventional supply chain mode,with statistically significant differences(t=14.685,8.716,P<0.01).The satisfaction scores of medical staffs from different departments for medical consumables of adopting the SPD supply chain mode were higher than those of adopting conventional supply chain mode,with a statistically significant difference(t=7.674,P<0.05).Conclusion:The application of the SPD supply chain mode for medical consumables in hospital can reduce the inventory amount,inventory quantity,loss rate,and return or change rate of medical consumables,and improve the satisfaction of medical staffs.