OBJECTIVE To explore the influencing factors for immune-related endocrine toxicity in the treatment of malignant solid tumors with sintilimab， aiming to provide a reference for rational drug use. METHODS Case data were collected from patients with malignant solid tumors， who were treated with sintilimab at the First Affiliated Hospital of Jinzhou Medical University from January 1， 2020 to December 31， 2024， using the electronic medical record system. The patients were divided into an endocrine immune-related adverse events （irAEs） group and a non-endocrine irAEs group based on whether they developed immune-related endocrine toxicity after sintilimab administration. The statistical significance of predictive variables was examined through univariate and multivariate Logistic regression methods. RESULTS A total of 224 patients were enrolled， including 138 cases （61.6%） in the non-endocrine irAEs group and 86 cases （38.4%） in the endocrine irAEs group. After univariate and multivariate Logistic regression analysis， a treatment period of 1-12 cycles was identified as an independent influencing factor for immune-related endocrine toxicity [OR＝7.175， 95%CI （1.239， 41.563）， P ＜0.05 ] ， immune-related hyperglycemia [OR＝6.600， 95%CI （1.053， 41.359）， P ＜0.05 ] ， and immune-related subclinical hypothyroidism [OR＝20.200， 95%CI （3.224， 126.558）， P ＜0.05 ] . The combination with paclitaxel-based drugs was identified as an independent influencing factor for immune-related subclinical hyperthyroidism [OR＝6.410， 95%CI （1.790， 22.955）， P ＜0.05 ] . CONCLUSIONS Among patients treated with sintilimab， the treatment cycle is a risk factor for immune-related endocrine toxicity， immune-related hyperglycemia and immune-related subclinical hypothyroidism. The combination of paclitaxel-based drugs is a risk factor for immune-related subclinical hyperthyroidism. It is recommended that when applying sintilimab in clinical practice， especially during the first few treatment cycles， the relevant endocrine indicators should be dynamically monitored in a standardized manner. In addition， special attention should be paid to patients treated with the combination of paclitaxel-based drugs to be vigilant against the occurrence of endocrine adverse events.

OBJECTIVE Identify the incentive and constraint factors of artificial intelligence （AI） application in the pharmaceutical field， and promote the application of AI in the field of pharmacy. METHODS Based on the technology acceptance model （TAM）， technology-organization-environment （TOE） framework， and diffusion of innovation theory （DOI）， a TAM-TOE-DOI integrated framework was constructed through a four-stage research process of “theoretical review → dimension mapping → mechanism integration → proposition development”. Combining the analytical pathways of the above three theories in AI application in pharmacy with the integration mechanisms and core propositions of the TAM-TOE-DOI， literature review and deductive reasoning were employed to systematically identify the incentive and constraint factors of AI application in pharmacy from three levels：micro （TAM）， meso （TOE）， and macro （DOI）， and to propose optimization strategies. RESULTS & CONCLUSIONS At the micro level， the efficiency transformation and quality improvement brought by AI technology were the main incentive factors for perceived usefulness， while technological complexity and algorithmic opacity were the main constraint factors for perceived ease of use. At the meso level， the completeness of technological infrastructure， the strength of top management support and innovation climate， as well as external institutional pressure and competitive driving forces were the core incentive factors， whereas scarcity of organizational resources and talent shortage were the main constraint factors. At the macro level， relative advantage and observability were typical incentive factors， while technological complexity was a typical constraint factor. China’s health administration， medical insurance authorities， and other relevant departments should coordinate efforts at the macro， meso， and micro levels to advance AI application in pharmacy： optimizing human-computer interaction and implementing tiered training programs at the micro level； reinforcing organizational support systems and capacity building at the meso level； dismantling data barriers and building social trust at the macro level. Differentiated implementation pathways should be developed for medical institutions at different tiers.

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.

Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective:To explore the cognitive characteristics, influencing factors, and treatment needs regarding biologic agents among patients with psoriasis.Methods:A cross-sectional study was conducted. Patients with psoriasis attending the Department of Dermatology, Xijing Hospital, Air Force Medical University were selected from October to December 2022, and from June to December 2023. A self-designed electronic questionnaire was used for investigation, covering demographic characteristics, psoriasis history (disease types, disease duration, previous treatments, etc.), biologics knowledge (sources of awareness, core cognitive dimensions), and treatment needs.Results:The valid questionnaire response rate reached 93.2% (439/471). The ages of enrolled patients were 35.95 ± 12.57 years, and the disease duration was 7.90 ± 3.26 years. Psoriasis vulgaris was the predominant type (363 cases, 82.69%). The overall awareness rate of biologics slightly increased from 68.62% (105/153) in 2022 to 72.38% (207/286) in 2023 ( P > 0.05). Primary information sources included new media (WeChat/internet) platforms (168 cases, 53.84%) and peer-to-peer sharing (115 cases, 36.86%), while physician counseling merely accounted for 9.29% (29 cases) ( P < 0.001). Insufficient knowledge of biologics was manifested primarily as poor awareness of comorbidities (47.60%, 209/439) and treatment monitoring protocols (22.32%, 98/439). Core concerns regarding biologic therapy included safety (73.34%, 322/439), economic burden (65.14%, 286/439), and long-term efficacy (63.55%, 279/439) ; 60.13% (264/439) of the patients expected rapid improvement of skin symptoms. As for treatment modalities, 90.20% (396/439) of the patients preferred regimens with extended dosing intervals. Conclusions:The patients with psoriasis demonstrated an imbalance in their cognitive structure regarding biologic agents. Their treatment needs exhibited multidimensional characteristics, emphasizing not only rapid clearance of skin lesions but also greater importance of treatment safety and cost-effectiveness.

Objective To analyze ancient prescriptions for knee osteoarthritis(KOA),and explore their application patterns,for providing clinical reference value.Methods Prescriptions were collected from ancient documents,and a database was created by using Excel 2016 for frequency analysis.Association rules and hidden structures were analyzed by using SPSS Modeler 18.0 and Lantern 5.0.Results A total of 373 prescriptions and 421 herbs were collected,with 3894 times of frequency of medication.Danggui was the most frequently used herb.Herbs primarily tonified deficiencies,relieved exterior symptoms,and expelled wind-dampness,with warm properties and pungent,sweet,or bitter tastes,mainly targeting the spleen and kidney meridians.Thirteen strong association rules were identified,including Chuanxiong+Niuxi-Danggui,and Bixie-Niuxi.Hidden structure analysis revealed 10 variables,leading to 4 clusters and 4 core prescriptions.Common syndromes included wind-damp,wind-cold-damp,wind-damp-heat,and qi-blood deficiency.Conclusion The treatment of KOA in ancient literature focuses on dispelling wind and removing dampness,taking into account both positive deficiency and evil excess,flexible use of tonifying spleen and kidney,clearing dampness-heat,tonifying Qi and blood and other drugs.

OBJECTIVE To investigate the horizontal transfer mechanisms and genetic evolutionary characteristics of virulence genes in hypervirulent Klebsiella pneumoniae(HvKP)and resistance genes in carbapenem-resistant K.pneumoniae(CRKP).METHODS The donor strain was a CRKP strain harboring both VIM and KPC resist-ance genes.The positive control was a CRKP strain containing blaIMP-4.The recipient strain was Escherichia coli J53.The horizontal transfer capability of the resistance genes was verified by plasmid conjugation assay.Fifty HvKP strains were collected from the First Affiliated Hospital of Jinan University from 2017 to 2021 and conjuga-ted with the plasmids of five CRKP strains which could mediate the transmission of drug resistance genes.The conjugants were screened by selective medium containing meropenem,and polymerase chain reaction(PCR)was used to detect the resistance and virulence genes in the conjugation-successful strains.The lethality of conjugants was verified by Galleria mellonella larval assays.RESULTS The donor CRKP strain had the ability to mediate re-sistance gene transmission.Its blaKPC gene was successfully transferred to E.coli J53,but the transference of the VIM gene failed.Five CRKP strains with the ability to mediate resistance gene transmission were screened,of which one strain carried both VIM and KPC resistance genes,and the other four strains carried the IMP-4 resist-ance gene.Only one CRKP strain with the blaIMP-4 resistance gene was successfully conjugated with HvKP,carry-ing both virulence genes(aerobactin and RmpA)and the blaIMP-4 resistance gene,with positive wire drawing test result.The Galleria mellonella larvae test showed that the conjugation-successful strain caused the death of all lar-vae within 24 hours.CONCLUSIONS In the hospital environment,CRKP and HvKP can form"superbugs"with both drug resistance and high virulence through plasmid conjugation,posing a severe challenge to clinical an-ti-infection treatment.It is necessary to strengthen the prevention and control of hospital-acquired infections.

Objective:To evaluate the effect of a health management model based on the Integrated Theory of Health Behavior Change (ITHBC) on body mass index (BMI), blood lipids, quality of life, and self-management ability in elderly community-dwelling patients with chronic coronary syndrome (CCS).Methods:This randomized controlled trial enrolled elderly CCS patients attending the general outpatient clinic at Fangzhuang Community Health Service Center of Fengtai District, Beijing, between March 2023 and May 2024. Participants were randomly assigned to either an intervention group or a control group. The control group received routine care, while the intervention group received ITHBC-based health management for 12 months. Primary endpoints included BMI, blood lipid profiles (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)), quality of life (assessed across 5 domains: disease perception, physical limitation, angina stability, angina frequency, and treatment satisfaction), and patient self-management ability (assessed across 7 domains: symptom management, harmful habit management, emergency management, disease knowledge management, daily life management, treatment adherence management, and emotional cognition management).Results:A total of 140 patients were enrolled, with the age of 71.0(67.0, 75.0) years; 85 (60.71%) were male. Seventy patients were assigned to each group. At the 12-month follow-up, levels of TC, TG, and LDL-C in the intervention group were significantly lower than those in the control group (all P<0.05). No statistically significant differences were observed in BMI or HDL-C levels between the two groups (all P>0.05). Regarding quality of life, the intervention group had a significantly lower score in the disease perception domain than the control group ( P=0.007). No significant intergroup differences were found in the scores for physical limitation, angina stability, angina frequency, or treatment satisfaction (all P>0.05). For self-management ability, the symptom management score was significantly higher in the intervention group than in the control group ( P=0.030). No significant differences were observed between the groups in the remaining self-management domains (all P>0.05). Conclusions:The ITHBC-based health management model can improve blood lipid management in elderly community-dwelling CCS patients, with superior effects compared to routine care, although it doesn′t significantly improve BMI. The model also shows potential to improve patients′ quality of life and self-management ability; however, its effects in these areas are not significantly superior to those of routine care.