The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Objective:To study and establish the quality standard of Polyoxyl 15 hydroxystearate(HS15),a phar-maceutical excipient,and systematically evaluate its functionality-related characteristics and safety.HS15 was applied to the preparation of docetaxel(DTX)injection to further investigate the safety and pharmacokinetic char-acteristics of the injection in vitro and in vivo.Methods:Based on the general USP-NF2024,EP11.0 and the fourth general rules of the Chinese Pharmacopoeia 2020 edition,the quality standards of HS15 were studied.Combined with the functional properties of surfactants,the critical micelle concentration of HS15 was investigated,and its safety was investigated by hemolysis test and vascular irritation test in vitro.HS15 was further applied to the preparation of DTX injection,and the safety and efficacy of the preparation were comprehensively evaluated by in vitro cytotoxicity test and in vivo pharmacokinetic study.Results:According to the experimental results and the pharmacopoeia of various countries,the quality standard of HS15 was preliminarily formulated.When the concen-tration of HS15 was 1 mg·mL-1,the hemolysis rate was about0.2%,the vascular irritation was small,and the DTX injection was safe in vitro and in vivo.The pharmacokinetic behavior was in line with expectations.Conclusion:This study successfully established the quality standard of HS15,and its functional correlation index research and safety evaluation strategy can provide reference for the quality control of similar excipients.The appli-cation of HS15 in the preparation of DTX injection provides a theoretical and experimental basis for its application in the development of insoluble antitumor drug injection.

Objective:To establish a method for evaluating the material attributes and skeletal performance of 2208 hydroxypropyl methylcellulose(HPMC),to clarify the influence of different material attributes on the skeletal per-formance of HPMC,to compare the differences between the products of different manufacturers,and to analyze the factors affecting the process.Methods:In this study,the material attributes such as powder chemical properties,viscosity,gelation temperature,thermodynamic properties,weight-average molecular weight,methoxy and hydroxypropoxy contents of different manufacturers were firstly investigated.Then,the water absorption,swelling,and dissolution properties of HPMC blank skeleton tablets were determined using the weighing method.Finally,Principal Component Analysis(PCA)and Orthogonal Partial Least-Squares Discrimination Analysis(OPLS-DA)were used to systematically evaluate the material attributes and skeleton performance of HPMC.The systematic evaluation of each material attribute and skeleton performance of HPMC was carried out to elucidate the intrinsic relationship between each material attribute and skeleton performance of HPMC.Results:The results showed that there were obvious differences in the material attributes of HPMC from different manufacturers,such as the proper-ties of powder,viscosity,and weight-average molecular weight,and that there were differences in the corrosion performance,water absorption,and swelling performance of the skeleton tablets prepared from different manufactur-ers,with the most obvious differences between K4Mand K100M.The results of the PCA and OPLS-DA analyses indicated that these 19 variables showed some correlation with each other.Both mathematical models showed better differentiation and classification effects on HPMC samples,and the OPLS-DA model had better classification effects than the PCA model.Conclusion:Based on the PCA and OPLS-DA models,this study conducted systematical research on HPMC,clarified the degree of influence of different material attributes on the skeletal performance of HPMC,and suggested the addition of HPMC particle size and size distribution,and weight-average molecular weight as the quality standards,which provide a basis for the quality control of the related excipients,the screening of formulation prescriptions,and the improvement of performance.

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition, the Chinese Pharmacopoeia 2025 Edition has been completed. Among them, 52 new pharmaceutical excipients monographs have been added, an increase of 15.5% compared with the 2020 Edition, and the total number has reached 387. This article focuses on the general framework and the main characteristics of the standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025 Edition, which can contribute to accurately understand and utilize the standards in Chinese Pharmacopoeia.

Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.

BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition,the Chinese Pharmacopoeia 2025 Edition has been completed.Among them,52 new pharmaceutical excip-ients monographs have been added,an increase of 15.5%compared with the 2020 Edition,and the total number has reached 387.This article focuses on the general framework and the main characteristics of the standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025 Edition,which can contribute to accurately under-stand and utilize the standards in Chinese Pharmacopoeia.

Cationic carriers have demonstrated broad application prospects in drug delivery due to their excellent drug-loading capacity and delivery performance. However, their high-density positive surface charge often leads to systemic toxicity and nonspecific uptake, posing significant barriers to clinical translation. In recent years, the emergence of charge shielding and stimuli-responsive strategies has provided effective avenues for modulating biocompatibility and targeting specificity. This review systematically summarizes the applications of chemical modification, natural polymer coating, and biomimetic membrane strategies in charge shielding. Furthermore, it explores the roles of endogenous stimuli such as pH, enzymes, and reactive oxygen species, as well as exogenous triggers like light and ultrasound, in achieving precise activation and controlled release. With the integration of multi-functional modules and the development of intelligent delivery platforms, cationic carriers are progressively advancing from laboratory research toward clinical translation. This review also discusses the translational potential and critical technical bottlenecks of related delivery systems, aiming to provide a theoretical framework and some reference for the design of next-generation smart delivery systems.

Objective:To study the functional characteristics of protective,barrier,and controlled release of film forming pharmaceutical excipients in formulations,establish a method for measuring the properties of film forming pharmaceutical excipients,and evaluate their performance.Methods:By preparing free films of different film forming pharmaceutical excipients and referring to national standards and literature research systems,a testing sys-tem covering key indicators such as tensile strength and elongation,water vapor permeability,flexibility,and solu-bility was constructed.Results:Through comparative testing of multiple brands of excipients,all detection methods showed good discriminability and reproducibility,indicating the applicability and stability of the methods.Conclusion:Evaluating the properties of film forming pharmaceutical excipients through a successfully constructed method not only reveals the structure-activity relationship between material structure and functional characteristics,but also provides technical support for the construction of functional index databases for pharmaceutical excipients.This research result can be used to guide the development of new film forming pharmaceutical excipients and pro-vide experimental basis for industry standard setting,meeting the needs of drug research and quality supervision.