OBJECTIVE To analyze and identify the metabolites of pirtobrutinib （PTN） in rats， and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma， urine， and feces. RESULTS A total of 29 PTN metabolites were identified， including 17， 19 and 22 metabolites in plasma， urine and feces， respectively. The metabolic pathways of PTN mainly included oxidation， sulfation， glucuronidation， etc.， and its metabolites were mostly combination products of two or more different metabolic forms. In detail， a total of 26 metabolites were associated with phase Ⅰ metabolic reactions （14 oxidation metabolites， 9 reduction/dehydrogenation metabolites， 8 demethylation metabolites， and 5 hydrolysis metabolites）. Meanwhile， a total of 20 products were involved in phase Ⅱ metabolites （14 sulfation metabolites and 8 glucuronic acid binding metabolites）. CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples， with the primary metabolic pathways being oxidation， sulfation， glucuronidation， and others.

OBJECITVE: To investigate the effectiveness of three-dimensional (3D) printing-assisted vascularized fibular graft for repairing metatarsal defects. METHODS: Between November 2021 and February 2024, 11 patients with varying degrees of metatarsal defects caused by trauma were treated. There were 10 males and 1 female, aged 22-67 years, with a mean age of 51.2 years. The defect locations were as follows: the first metatarsal in 4 cases, the fifth metatarsal in 2 cases, the first and the second metatarsals in 1 case, the first to third metatarsals in 1 case, the third and the fourth metatarsals in 1 case, the third to fifth metatarsals in 1 case, and the first to fifth metatarsals in 1 case. The preoperative American Orthopaedic Foot & Ankle Society (AOFAS) score was 67.0 (48.5, 72.5). Based on 3D-printed bilateral feet models and mirrored healthy-side foot arch angles for preoperative planning and design, the vascularized fibular graft was performed to repair the metatarsal defects. At last follow-up, the medial and lateral longitudinal arches of bilateral feet were measured on weight-bearing X-ray films, and functional assessment was conducted using the AOFAS score. RESULTS: All operations were successfully completed, with an operation time ranging from 180 to 465 minutes (mean, 246.8 minutes). All incisions healed by first intention, with no occurrence of osteomyelitis. All patients were followed up 6-22 months (mean, 10 months). X-ray film reviews showed bone graft healing in all cases, with a healing time of 3-6 months (mean, 5 months). All patients underwent internal fixator removal at 6-12 months after operation. At last follow-up, no significant difference was observed in the medial and lateral longitudinal arches between the healthy and affected feet ( P>0.05). The AOFAS score of the affected foot was 78.0 (73.5, 84.0), showing a significant improvement compared to the preoperative score ( P<0.05). The effectiveness was rated as excellent in 1 case, good in 7 cases, fair in 2 cases, and poor in 1 case. Linear scarring remained at the donor site, with no functional impairment in adjacent joint movement. CONCLUSION 3D printing-assisted vascularized fibular graft for repairing metatarsal defects can effectively restore the physiological angle of the foot arch, facilitate the recovery of weight-bearing alignment, promote good bone healing, and yield satisfactory clinical outcomes.
Humans ; Printing, Three-Dimensional ; Middle Aged ; Male ; Fibula/blood supply* ; Female ; Metatarsal Bones/injuries* ; Adult ; Bone Transplantation/methods* ; Aged ; Plastic Surgery Procedures/methods* ; Young Adult ; Treatment Outcome

Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

Objective To summarise a clinical experience of nursing care for 3 children who were treated with ECMO for sepsis and complicated with fulminant myocarditis.Methods Clinical data in nursing cares for 3 children treated with ECMO for sepsis and complicated with fulminant myocarditis were collected and analysed,with the spotted difficulties in nursing care and proposed coping strategies.Results The 3 children survived and were transferred out of the(pediatric intensive care unit,PICU)with stable vital signs and haemodynamics after emergency treatment with ECMO and continuous renal replacement therapy(CRRT).Conclusion Children with sepsis leading to myocardial depression and subsequent heart failure require close observation of the changes and consequently specialised cares after having initiated an ECMO in emergency treatment.This includes ensuring proper fixation of the cannulas,managing anticoagulation,monitoring the speed,flow rate and pressure of ECMO,management of body temperature,skin care,sedation and pain,as well as prevention of complications.These nursing care measures would improve the survival rate after the treatment of ECMO.

Objective:To analyze the differential expressions of proteins in aqueous humor in patients with exfoliation syndrome (XFS).Methods:A total of 20 patients were enrolled in the Department of Ophthalmology, People's Hospital of Hotan District from June 2020 to January 2021, including 10 patients with age-related cataract and 10 XFS patients combined with cataract, which were classified as cataract group and XFS group, respectively.A total of 50 to 100 μl aqueous humor was obtained in the middle of the anterior chamber through the intraoperative phacoemulsification channel.The proteins extracted from aqueous humor were analyzed by label-free quantitative proteomics technology.The cataract group was set as the control group, and the differentially expressed proteins (DEPs) in XFS group were screened according to P<0.05 and fold change >1.5.Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were used to explore the function and regulatory signaling pathways of DEPs in the XFS group.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-21).Written informed consent was obtained from each subject. Results:In comparison with the cataract group, 25 DEPs were identified in the XFS group, primarily involved in cell adhesion, receptor, hydrolase, and molecular transport.Specifically, there were 14 down-regulated proteins including complement factor H-related protein 1 (CFHR1), endoplasmic reticulum chaperone BiP (HSPA5), biglycan (BGN), FRAS1-related extracellular matrix protein 2 (FREM2), hemoglobin subunit delta (HBD), hemoglobin subunit gamma-1 (HBG1), lysosomal thioesterase PPT2 (PPT2) etc., and 11 up-regulated proteins including latent-transforming growth factor beta-binding protein 2 (LTBP2), very low-density lipoprotein receptor (VLDLR), laminin subunit alpha-2 (LAMA2), coagulation factor Ⅸ (F9).Among them, FREM2 was the most significantly differentially expressed protein in XFS group with consistent expression levels across individual samples.GO analysis revealed that these DEPs mainly localized to the extracellular matrix of collagen, bound globin-hemoglobin complex, plasma lipoprotein particles and lysosomes.Molecular functions and biological processes showed that HBD and HBG1 were involved in cellular detoxification, PPT2 in hydrolase activity, and BGN and LTBP2 in glycosaminoglycan binding.KEGG signaling pathway analysis indicated that CFHR1 and F9 were associated with complement and coagulation cascade pathways, and FREM2 and LAMA2 were linked to the extracellular matrix interaction pathway.Conclusions:Disease progression of XFS may be associated with changes in extracellular matrix proteins, disruption of the blood-aqueous humor barrier, and potential inflammatory responses.The significant down-regulation of FREM2 protein may be a potential biomarker for XFS.

Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.
Pharmaceutical Preparations ; Peptides/chemistry* ; Amino Acid Sequence ; Nanostructures/chemistry* ; Drug Delivery Systems

Objective:As a newly emerging thing, the construction and operation management of research wards are still being explored. According to the previous practice, this study summarized and shared the key points of a demonstration research ward in Beijing, and provided a reference for the development of domestic research wards.Methods:Focusing on improving the efficiency and quality of clinical research, this article summarizes and shares the experience of research ward construction. In addition, this study explores how to maintain the high-quality sustainable development of research wards from the aspects of improving core competence, system construction, and talent training.Results:Professional teams, innovative operation modes, as well as intelligence and informatization could improve the quality of clinical research. Besides, the improvement of core competence, talent training, and policy support ensure sustainable development of research wards.Conclusions:As clinical research platforms, the development paths of research wards need to be clarified further. The standardized construction and sustainable development of research wards can effectively improve clinical research capability and promote the transformation of scientific achievements.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.