Yttrium-90 selective internal radiation therapy (⁹⁰Y-SIRT) is a treatment technique that delivers radioactive microspheres precisely to the arterial vascular bed of neoplasms, utilizing beta radiation to administer a high local dose of radiation to the neoplasm tissues. This technology has demonstrated significant efficacy in patients with unresectable pirmary liver cancers and liver metastases. This article systematically reviews the development history and clinical application status of ⁹⁰Y-SIRT in the treatment of liver cancer, and looks forward to future development directions.

Natural product-based drug combinations (NPDCs) present distinctive advantages in treating complex diseases. While high-throughput screening (HTS) and conventional computational methods have partially accelerated synergistic drug combination discovery, their applications remain constrained by experimental data fragmentation, high costs, and extensive combinatorial space. Recent developments in artificial intelligence (AI), encompassing traditional machine learning and deep learning algorithms, have been extensively applied in NPDC identification. Through the integration of multi-source heterogeneous data and autonomous feature extraction, prediction accuracy has markedly improved, offering a robust technical approach for novel NPDC discovery. This review comprehensively examines recent advances in AI-driven NPDC prediction, presents relevant data resources and algorithmic frameworks, and evaluates current limitations and future prospects. AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
Artificial Intelligence ; Biological Products/chemistry* ; Humans ; Drug Combinations ; Drug Discovery/methods* ; Machine Learning ; Algorithms

As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term "immunosuppression" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.
Ferroptosis/immunology* ; Humans ; Immune Tolerance/immunology* ; Animals ; Immunosuppression Therapy ; Iron/metabolism* ; Neoplasms/immunology*

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Hemoglobin, the principal protein in red blood cells, is crucial for oxygen transport in the bloodstream. The quantification of hemoglobin concentration is indispensable in medical diagnostics and health management, which encompass the diagnosis of anemia and the screening of various blood disorders. Immunological methods, based on antigen-antibody interactions, are distinguished by their high sensitivity and accuracy. Consequently, it is necessary to develop hemoglobin-specific antibodies characterized by high specificity and affinity to enhance detection accuracy. In this study, we immunized a Bactrian camel (Camelus bactrianus) with human hemoglobin and subsequently constructed a nanobody library. Utilizing a solid-phase screening method, we selected nanobodies and evaluated the binding activity of the screened nanobodies to hemoglobin. Initially, human hemoglobin was used to immunize a Bactrian camel. Following four immunization sessions, blood was withdrawn from the jugular vein, and a nanobody library with a capacity of 2.85×10⁸ colony forming units (CFU) was generated. Subsequently, ten hemoglobin-specific nanobody sequences were identified through three rounds of adsorption-elution-enrichment assays, and these nanobodies were subjected to eukaryotic expression. Finally, enzyme-linked immunosorbent assay and biolayer interferometry were employed to evaluate the stability, binding activity, and specificity of these nanobodies. The results demonstrated that the nanobodies maintained robust binding activity within the temperature range of 20-40 ℃ and exhibited the highest binding activity at pH 7.0. Furthermore, the nanobodies were capable of tolerating a 10% methanol solution. Notably, among the nanobodies tested, VHH-12 displayed the highest binding activity to hemoglobin, with a half maximal effective concentration (EC₅₀) of 10.63 nmol/L and a equilibrium dissociation constant (K_D) of 2.94×10^-7 mol/L. VHH-12 exhibited no cross-reactivity with a panel of eight proteins, such as ovalbumin and bovine serum albumin, while demonstrating partial cross-reactivity with hemoglobin derived from porcine, goat, rabbit, and bovine sources. In this study, a hemoglobin-specific high-affinity nanobody was successfully isolated, demonstrating potential applications in disease diagnosis and health monitoring.
Animals ; Camelus/immunology* ; Single-Domain Antibodies/immunology* ; Hemoglobins/immunology* ; Humans ; Peptide Library

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective:To find out how newly recruited nurses feel about the use of scenario simulation teaching in communication skill training, and to provide references and lessons for improving and perfecting the training of newly recruited nurses.Methods:Purposive sampling method was used to select 10 nurses who were newly recruited to a tertiary grade A hospital in Shanghai in July 2023 for semi-structured interviews. Colaizzi's 7-step analysis method was used to collate and analyze the data and develop themes.Results:Three themes were extracted from the feelings of newly recruited nurses about scenario simulation teaching, which were the improvement of learning ability, the cultivation of clinical comprehensive ability, and the improvement of communication and teamwork ability.Conclusions:Scenario simulation teaching can improve the clinical communication ability of newly recruited nurses and enhance their learning ability and comprehensive clinical ability. This study designed a scenario simulation teaching program oriented and targeted to highlight communication ability, which further proved its positive significance. However, attention needs to be paid to the construction of clinical teaching team, evaluation system, and feedback mechanism for targeted improvement to enhance the teaching effect.

Objective:To investigate the correlations between serum 25-hydroxy vitamin D, interleukin-23 (IL-23), coagulation function indicators, and the severity of rheumatoid arthritis (RA) and treatment effect.Methods:A total of 56 patients with RA who received treatment at Xianyang Central Hospital between February 2019 and January 2023 were included in the RA group, and an additional 56 healthy participants who concurrently underwent physical examination in the same hospital were included in the control group. Serum levels of 25(OH)D, IL-23, and coagulation function indicators were measured in both groups. The severity of RA was evaluated using the Disease Activity Score in 28 Joints (DAS28). The treatment outcomes were assessed based on post-treatment DAS28 scores. Significant differences in serum 25(OH)D, IL-23, and coagulation function indicators were compared among patients with different degrees of disease severity and treatment outcomes. Furthermore, a thorough analysis was conducted to identify risk factors associated with treatment failure in RA patients.Results:The serum 25(OH)D level in the RA group was significantly lower than that in the control group [(21.63 ± 2.29) μg/L vs. (33.06 ± 3.82) μg/L, t = 19.21, P < 0.05]. Prothrombin time (PT), activated partial thromboplastin time (APTT), IL-23, and fibrinogen (FIB) were significantly higher in the RA group [(46.68 ± 5.01) ng/L, (36.85 ± 3.79) seconds, (16.81 ± 1.73) seconds, (5.46 ± 0.58) g/L] compared with the control group ( t = -36.88, -6.19, -11.20, -11.93, all P < 0.05). The serum 25(OH)D levels decreased significantly, with the highest levels observed in the stable group [(30.91 ± 3.12) μg/L], followed by the low activity group [(24.14 ± 2.56) μg/L], the medium activity group [(18.69 ± 1.93) μg/L], and the lowest levels in the high activity group [(15.62 ± 1.63) μg/L, F = 107.90, P < 0.05]. PT, APTT, IL-23 and FIB levels decreased significantly, with the longest periods or highest levels observed in the high activity group [(58.08 ± 6.03) ng/L, (39.92 ± 4.08) seconds, (18.83 ± 2.01) seconds, (6.19 ± 0.63) g/L, F = 72.18, P < 0.05], followed by the medium activity group [(51.25 ± 5.27) ng/L, (37.74 ± 3.91) seconds, (17.15 ± 1.82) seconds, (5.74 ± 0.59) g/L, F = 4.98, P < 0.05], the low activity group [(41.82 ± 4.63) ng/L, (35.41 ± 3.75) seconds, (16.24 ± 1.71) seconds, (5.07 ± 0.54) g/L, F = 14.26, P < 0.05], and the lowest periods or lowest levels in the stable group [(30.67 ± 3.17) ng/L, (33.19 ± 3.42) seconds, (14.29 ± 1.51) seconds, (4.56 ± 0.51) g/L, F = 20.48, P < 0.05]. Serum 25(OH)D level was significantly lower in the treatment failure group than that in the effective treatment group [(18.90 ± 1.97) μg/L vs. (22.63 ± 2.34) μg/L, t = 5.49, P < 0.05]. PT, APTT, IL-23, and FIB in the treatment failure group were significantly higher than those in the effective treatment group [(55.21 ± 5.71) g/L, (40.62 ± 4.17) seconds, (18.56 ± 1.93) seconds, (6.33 ± 0.69) g/L, t = -7.62, -4.48, -4.46, -6.24, all P < 0.05]. IL-23, FIB, PT, and APTT were identified as independent risk factors for treatment failure in RA patients ( OR > 1, P < 0.05), whereas 25(OH)D emerged as a protective factor against treatment failure ( OR < 1, P < 0.05). Conclusion:Significant differences in serum 25(OH)D, IL-23, and coagulation function indicators were observed between RA patients and healthy individuals. These indicators were also closely associated with the severity and treatment outcomes of RA. Therefore, they can be used to assess the disease status and treatment outcomes of RA patients.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objectives:To evaluate the tricuspid valve(TV)geometric remodeling in patients with idiopathic pulmonary arterial hypertension(IPAH)by three-dimensional transthoracic echocardiography. Methods:Two-dimensional and three-dimensional transthoracic echocardiography were performed in 30 IPAH patients and 15 healthy controls,and the geometry parameters of TV were obtained by four-dimensional auto tricuspid valve quantitative(4D Auto-TVQ)in the right ventricular-focused apical view.Pulmonary arterial hypertension was determined by right heart catheterization within 48 hours of echocardiography. Results:The 4-chamber diameter,tricuspid annular(TA)perimeter,TA area,maximal tenting height,coaptation point height and tenting volume were larger in IPAH patients than those in healthy controls(all P＜0.05),2-chamber diameter was similar between two groups.In IPAH group,maximal tenting height and coaptation point height were moderately correlated with right ventricular end-diastolic volume(r=0.710,r=0.515,both P＜0.05),while TA perimeter,4-chamber diameter and TA area were moderately correlated with right atrial end-systolic volume(r=0.712,r=0.558,r=0.545,all P＜0.05). Conclusions:IPAH patients have larger maximal tenting height,coaptation point height and tenting volume,TA enlargement is mainly visible in 4-chamber diameter.TV tenting height is associated with right ventricular volume,but TA size is associated with right atrial volume in IPAH patients.