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 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.

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:This current study aims to explore the approaches for constructing a professional clinical research system within the context of research ward development, with the ultimate objective of providing valuable guidance for the establishment and development of proficient clinical research teams.Methods:Through a comprehensive case analysis, integrating the practical experiences from clinical trials conducted in the research ward of a Class-A tertiary hospital in Beijing, along with an extensive review of relevant literature and policy studies, this paper examined the current state of domestic clinical research implementation teams. Subsequently, a series of strategies were devised to build and foster professional clinical research teams and to explore corrective measures for cultivating a dynamic professional clinical research talent ecosystem.Results:The development of full-time clinical research teams in China was rather slow, and there was a lack of mature clinical trial teams training blueprints. Drawing on the practical experience accumulated during the establishment of a professional clinical research team in a leading hospital in Beijing, it was crucial to attach utmost importance to the optimal allocation of human and material resources. This required the systematic training of principal investigators, coordinating researchers, and research assistants, as well as the setting up of a comprehensive support system, an advanced scientific research team, and a quality control unit. Moreover, the standardization of operational models of both domestic and foreign research institutions, along with the implementation of corresponding support and incentive mechanisms, and the strengthening of training and continuing education frameworks were equally significant.Conclusions:During the process of assembling a full-time clinical research team, it is of utmost significance to cultivate professional principal investigators, coordinating researchers, and research assistants. Complemented by the establishment of a comprehensive support team, a scientific research team, and a quality control team, along with corresponding support and incentive mechanisms, this is crucial for constructing a professional clinical research execution team and a sustainable talent ecosystem in the research ward. Eventually, this will drive the efficient and high-quality progress of China's pharmaceutical industry.

Objective:This current study aims to explore the approaches for constructing a professional clinical research system within the context of research ward development, with the ultimate objective of providing valuable guidance for the establishment and development of proficient clinical research teams.Methods:Through a comprehensive case analysis, integrating the practical experiences from clinical trials conducted in the research ward of a Class-A tertiary hospital in Beijing, along with an extensive review of relevant literature and policy studies, this paper examined the current state of domestic clinical research implementation teams. Subsequently, a series of strategies were devised to build and foster professional clinical research teams and to explore corrective measures for cultivating a dynamic professional clinical research talent ecosystem.Results:The development of full-time clinical research teams in China was rather slow, and there was a lack of mature clinical trial teams training blueprints. Drawing on the practical experience accumulated during the establishment of a professional clinical research team in a leading hospital in Beijing, it was crucial to attach utmost importance to the optimal allocation of human and material resources. This required the systematic training of principal investigators, coordinating researchers, and research assistants, as well as the setting up of a comprehensive support system, an advanced scientific research team, and a quality control unit. Moreover, the standardization of operational models of both domestic and foreign research institutions, along with the implementation of corresponding support and incentive mechanisms, and the strengthening of training and continuing education frameworks were equally significant.Conclusions:During the process of assembling a full-time clinical research team, it is of utmost significance to cultivate professional principal investigators, coordinating researchers, and research assistants. Complemented by the establishment of a comprehensive support team, a scientific research team, and a quality control team, along with corresponding support and incentive mechanisms, this is crucial for constructing a professional clinical research execution team and a sustainable talent ecosystem in the research ward. Eventually, this will drive the efficient and high-quality progress of China's pharmaceutical industry.

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.

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 investigate the effects of celastrol (CSR) on dendritic cell (DC) and T follicular helper cell (Tfh) subsets in the mouse of ulcerative colitis (UC) .Methods:Forty-eight male BALB/c mice were randomly divided into healthy control group, model group, and CSR intervention group, with 16 mice in each group. The healthy control group was fed with normal purified water, while the mice in model group and CSR intervention group were fed with 3% DSS solution to induce UC model. Since the induction, the mice in CSR intervention group were gavaged with 1mg/kg of CSR, and the mice in UC group were gavaged with equal volume of saline once a day. The weight and stool characteristics of the mice were recorded, and disease activity index (DAI) were evaluated. After the 8-day intervention, the length of the mouse colon was measured, the histopathological changes were observed, and the histopathological score was evaluated. Flow cytometry was used to detect the percentage of DC, conventional DC (CD8α + cDC1, CD103 + cDC1, cDC2), plasmacytoid DC (pDC), and Tfh subsets in colon lamina propria, mesenteric lymph nodes and spleen. Cytometric bead array kit was used to detect the expression levels of DC and Tfh related cytokines [interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 21 (IL-21) ] in colon tissue. The influence of CSR on naive CD4 +T cell proliferation and Tfh differentiation were validated in vitro experiments. Results:The modelling success rate was 100% and all mice survived. Compared with model group, mice in CSR intervention group had heavier weight, lower DAI, and ameliorated colonic length shortening, with all differences being statistically significant (all P < 0.05). The intestinal mucosal structure of mice in model group was disordered, with a large number of inflammatory cell infiltration; the intestinal mucosal barrier of mice in CSR intervention group approached normal structure, with fewer inflammatory cells, and the histopathological scores were significantly decreased ( P<0.05). In the colon lamina propria, compared with model group, the percentages of DC, CD8α + cDC1 and Tfh decreased, while the percentage of CD103 + cDC1 increased in CSR intervention group, and these differences were all statistically significant (all P<0.05). In mesenteric lymph nodes, the percentage of CD8α + cDC1 decreased, while the percentages of DC, CD103 + cDC1, cDC2 and Tfh increased in CSR intervention group compared with model group, and these differences were all statistically significance (all P<0.05). In the spleen, compared with model group, the percentage of pDC was significantly reduced in CSR intervention group ( P<0.05) .The expression levels of IL-6, TNF-α and IL-21 in colon tissues of CSR intervention group were lower, while IL-10 was higher than those of model group, and these differences were statistically significant (all P<0.05). In vitro experiments, CSR could inhibit naive CD4 + T cell proliferation and Tfh differentiation, with statistically significant differences (all P < 0.05) . Conclusion:CSR can alleviate intestinal damage in UC mice, potentially by modulating the local immune microenvironment through regulating DC and Tfh subsets.

Objective:To investigate the effects of celastrol (CSR) on dendritic cell (DC) and T follicular helper cell (Tfh) subsets in the mouse of ulcerative colitis (UC) .Methods:Forty-eight male BALB/c mice were randomly divided into healthy control group, model group, and CSR intervention group, with 16 mice in each group. The healthy control group was fed with normal purified water, while the mice in model group and CSR intervention group were fed with 3% DSS solution to induce UC model. Since the induction, the mice in CSR intervention group were gavaged with 1mg/kg of CSR, and the mice in UC group were gavaged with equal volume of saline once a day. The weight and stool characteristics of the mice were recorded, and disease activity index (DAI) were evaluated. After the 8-day intervention, the length of the mouse colon was measured, the histopathological changes were observed, and the histopathological score was evaluated. Flow cytometry was used to detect the percentage of DC, conventional DC (CD8α + cDC1, CD103 + cDC1, cDC2), plasmacytoid DC (pDC), and Tfh subsets in colon lamina propria, mesenteric lymph nodes and spleen. Cytometric bead array kit was used to detect the expression levels of DC and Tfh related cytokines [interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 21 (IL-21) ] in colon tissue. The influence of CSR on naive CD4 +T cell proliferation and Tfh differentiation were validated in vitro experiments. Results:The modelling success rate was 100% and all mice survived. Compared with model group, mice in CSR intervention group had heavier weight, lower DAI, and ameliorated colonic length shortening, with all differences being statistically significant (all P < 0.05). The intestinal mucosal structure of mice in model group was disordered, with a large number of inflammatory cell infiltration; the intestinal mucosal barrier of mice in CSR intervention group approached normal structure, with fewer inflammatory cells, and the histopathological scores were significantly decreased ( P<0.05). In the colon lamina propria, compared with model group, the percentages of DC, CD8α + cDC1 and Tfh decreased, while the percentage of CD103 + cDC1 increased in CSR intervention group, and these differences were all statistically significant (all P<0.05). In mesenteric lymph nodes, the percentage of CD8α + cDC1 decreased, while the percentages of DC, CD103 + cDC1, cDC2 and Tfh increased in CSR intervention group compared with model group, and these differences were all statistically significance (all P<0.05). In the spleen, compared with model group, the percentage of pDC was significantly reduced in CSR intervention group ( P<0.05) .The expression levels of IL-6, TNF-α and IL-21 in colon tissues of CSR intervention group were lower, while IL-10 was higher than those of model group, and these differences were statistically significant (all P<0.05). In vitro experiments, CSR could inhibit naive CD4 + T cell proliferation and Tfh differentiation, with statistically significant differences (all P < 0.05) . Conclusion:CSR can alleviate intestinal damage in UC mice, potentially by modulating the local immune microenvironment through regulating DC and Tfh subsets.

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.