BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Objective:To investigate the age-specific distribution characteristics of plantar pressure parameters in healthy children aged 3-12 years.Methods:This cross-sectional study retrieved data from the hospital information system in January 2025 for 272 children aged 3-12 years who underwent physical examinations and voluntarily completed plantar pressure analysis at Beijing Children′s Hospital, Capital Medical University, from July 2022 to December 2024. Demographic and clinical data, including anthropometric measurements (height and weight), flatfoot diagnosis and plantar pressure parameters (maximum pressure, time to maximum force, and contact time percentage in bilateral forefoot, midfoot, and hindfoot) were recorded. Participants were categorized into 3 age groups (3-6 years, 7-9 years, and 10-12 years) and were grouped by gender as well. Intergroup comparisons used one-way ANOVA or least-significant difference test or χ2 tests. Spearman′s rank correlation assessed the relationship between flatfoot prevalence and age. Results:Among 272 children (143 boys, 129 girls), age groups comprised 3-6 years (118 children, 64 boys and 54 girls), 7-9 years (96 children, 49 boys and 47 girls), and 10-12 years (58 children, 30 boys and 28 girls). Flatfoot prevalence was higher in boys than in that of girls (41.3% (59/143) vs. 28.7% (37/129), χ2=4.70, P=0.030), and negatively correlated with age ( r=-0.21, P<0.001). There all had statistically differences in the maximum pressure values of the bilateral forefoot and hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). The maximum pressure values of bilateral midfoot in the group of aged 10-12 years were all higher than those of the other two groups (all P<0.001). There had no statistically differences in the time maximum force value of the bilateral forefoot among the 3 age groups (all P>0.05). The time maximum force values of bilateral midfoot in the group of aged 3-6 years were all lower than those of the other two groups (all P<0.05). There all had statistically differences in the time maximum force value of the bilateral hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). There all had statistically differences in the contact time percentage values of the bilateral forefoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). There had no statistically differences in the contact time percentage values of the bilateral midfoot among the 3 age groups (all P>0.05). There all had statistically differences in the contact time percentage values of the bilateral hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all lower than those of the other two groups (all P<0.05). Conclusion:Plantar pressure parameters exhibit distinct age-related patterns, reflecting the development of gait patterns and foot arch formation, which will be useful for monitoring physical growth and sports rehabilitation.

Objective To analyze the application value of 3D Slicer software in endoscopic transsphenoidal surgery for pituitary adenoma resection.Methods A retrospective analysis was made on the clinical data of 36 patients with pituitary adenomas treated with 3D Slicer-assisted endoscopic transsphenoidal surgery(3D Slicer group)in the Department of Neurosurgery,The Second Affiliated Hospital of Xi'an Jiaotong University,from January 2024 to December 2024.Preoperatively,multimodal images were fused and reconstructed using 3D Slicer software to systematically evaluate bony anatomical structures such as sphenoid sinus ostia,intrasphenoidal septa,and sellar floor structures,design the size of pedicled nasoseptal flaps,and clarify the positional relationships between pituitary adenomas and surrounding vital structures including the internal carotid artery,pituitary gland,and optic chiasm,so as to provide real-time guidance for intraoperative procedures.Meanwhile,45 patients with pituitary adenomas treated with neuronavigation-assisted endoscopic transsphenoidal surgery from January 2023 to December 2023 were included as the control group(neuronavigation group).The surgical outcomes and postoperative complications were compared between the two groups.Results Compared with the neuronavigation group,the 3D Slicer group demonstrated higher identification rates of the optic nerve groove and carotid artery impression(94.4％vs.77.8％),shorter operative time[(2.9±0.6)h vs.(3.5±0.9)h],less intraoperative bleeding[(159.7±70.5)mL vs.(237.8±96.0)mL],and a lower incidence of postoperative olfactory dysfunction(8.3％vs.26.7％),with statistically significant differences(P＜0.05).However,there were no statistically significant differences between the two groups in the identification rate of the sphenoid sinus ostium(100.0％vs.97.8％),gross total resection rate(75.0％vs.64.4％),and the incidence of other postoperative complications,including cerebrospinal fluid leakage(0.0％vs.6.7％),intracranial infection(2.8％vs.11.1％),transient diabetes insipidus(30.6％vs.22.2％),and hypopituitarism(38.9％vs.37.8％,P＞0.05).Conclusion 3D Slicer software helps improve the mastery of anatomical basics in endoscopic transsphenoidal approach among junior and primary physicians,enhancing the clinical efficacy and safety of pituitary adenoma resection,and thus is worthy of clinical promotion.

Objective To analyze the application value of 3D Slicer software in endoscopic transsphenoidal surgery for pituitary adenoma resection.Methods A retrospective analysis was made on the clinical data of 36 patients with pituitary adenomas treated with 3D Slicer-assisted endoscopic transsphenoidal surgery(3D Slicer group)in the Department of Neurosurgery,The Second Affiliated Hospital of Xi'an Jiaotong University,from January 2024 to December 2024.Preoperatively,multimodal images were fused and reconstructed using 3D Slicer software to systematically evaluate bony anatomical structures such as sphenoid sinus ostia,intrasphenoidal septa,and sellar floor structures,design the size of pedicled nasoseptal flaps,and clarify the positional relationships between pituitary adenomas and surrounding vital structures including the internal carotid artery,pituitary gland,and optic chiasm,so as to provide real-time guidance for intraoperative procedures.Meanwhile,45 patients with pituitary adenomas treated with neuronavigation-assisted endoscopic transsphenoidal surgery from January 2023 to December 2023 were included as the control group(neuronavigation group).The surgical outcomes and postoperative complications were compared between the two groups.Results Compared with the neuronavigation group,the 3D Slicer group demonstrated higher identification rates of the optic nerve groove and carotid artery impression(94.4％vs.77.8％),shorter operative time[(2.9±0.6)h vs.(3.5±0.9)h],less intraoperative bleeding[(159.7±70.5)mL vs.(237.8±96.0)mL],and a lower incidence of postoperative olfactory dysfunction(8.3％vs.26.7％),with statistically significant differences(P＜0.05).However,there were no statistically significant differences between the two groups in the identification rate of the sphenoid sinus ostium(100.0％vs.97.8％),gross total resection rate(75.0％vs.64.4％),and the incidence of other postoperative complications,including cerebrospinal fluid leakage(0.0％vs.6.7％),intracranial infection(2.8％vs.11.1％),transient diabetes insipidus(30.6％vs.22.2％),and hypopituitarism(38.9％vs.37.8％,P＞0.05).Conclusion 3D Slicer software helps improve the mastery of anatomical basics in endoscopic transsphenoidal approach among junior and primary physicians,enhancing the clinical efficacy and safety of pituitary adenoma resection,and thus is worthy of clinical promotion.

Objective:To investigate the age-specific distribution characteristics of plantar pressure parameters in healthy children aged 3-12 years.Methods:This cross-sectional study retrieved data from the hospital information system in January 2025 for 272 children aged 3-12 years who underwent physical examinations and voluntarily completed plantar pressure analysis at Beijing Children′s Hospital, Capital Medical University, from July 2022 to December 2024. Demographic and clinical data, including anthropometric measurements (height and weight), flatfoot diagnosis and plantar pressure parameters (maximum pressure, time to maximum force, and contact time percentage in bilateral forefoot, midfoot, and hindfoot) were recorded. Participants were categorized into 3 age groups (3-6 years, 7-9 years, and 10-12 years) and were grouped by gender as well. Intergroup comparisons used one-way ANOVA or least-significant difference test or χ2 tests. Spearman′s rank correlation assessed the relationship between flatfoot prevalence and age. Results:Among 272 children (143 boys, 129 girls), age groups comprised 3-6 years (118 children, 64 boys and 54 girls), 7-9 years (96 children, 49 boys and 47 girls), and 10-12 years (58 children, 30 boys and 28 girls). Flatfoot prevalence was higher in boys than in that of girls (41.3% (59/143) vs. 28.7% (37/129), χ2=4.70, P=0.030), and negatively correlated with age ( r=-0.21, P<0.001). There all had statistically differences in the maximum pressure values of the bilateral forefoot and hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). The maximum pressure values of bilateral midfoot in the group of aged 10-12 years were all higher than those of the other two groups (all P<0.001). There had no statistically differences in the time maximum force value of the bilateral forefoot among the 3 age groups (all P>0.05). The time maximum force values of bilateral midfoot in the group of aged 3-6 years were all lower than those of the other two groups (all P<0.05). There all had statistically differences in the time maximum force value of the bilateral hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). There all had statistically differences in the contact time percentage values of the bilateral forefoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all the lowest, and those of the group of aged 10-12 years were all the highest (all P<0.05). There had no statistically differences in the contact time percentage values of the bilateral midfoot among the 3 age groups (all P>0.05). There all had statistically differences in the contact time percentage values of the bilateral hindfoot among the 3 age groups (all P<0.001), and after pairwise comparison, those of the group of aged 3-6 years were all lower than those of the other two groups (all P<0.05). Conclusion:Plantar pressure parameters exhibit distinct age-related patterns, reflecting the development of gait patterns and foot arch formation, which will be useful for monitoring physical growth and sports rehabilitation.

This study aims to investigate the protective effect of resveratrol against liver injury in hindlimb unloading rats. Thirty 2-month-old male SD rats were randomly divided into normal group (Control), hindlimb unloading model group (Model), and hindlimb unloading+resveratrol administration group (Model+Res). The Model + Res group was injected intraperitoneally with 30 mg/kg of resveratrol, and the Control and Model groups were injected intraperitoneally with an equal volume of 0.9% NaCl. Liver tissues were collected after 28 days and analyzed for oxidative stress, inflammatory factors, energy metabolism indices, Na ⁺-K ⁺-ATPase and Ca ²⁺-Mg ²⁺-ATPase activity, and morphological changes were observed by hematoxylin-eosin staining. The protein expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blotting. Compared with the Control group, hepatocytes in the Model group showed swelling, abnormal morphology, nuclear consolidation, and cell membrane disruption. Oxidative stress, inflammatory factor levels, hepatic glycogen accumulation, and energy metabolism were increased in the liver tissues of the Model group, while resveratrol treatment significantly reversed these changes. The results of Western blotting showed that resveratrol significantly reduced the expression of Bax and increased the expression levels of Bcl-2, and the proteins of p-PI3K/PI3K and p-AKT/AKT expression levels. It is suggested that 28 days of hindlimb unloading treatment could lead to liver tissue injury in rats, which is manifested as oxidative stress, inflammatory response, energy metabolism disorder and increased apoptosis level, and resveratrol has a certain mitigating effect on this.
Animals ; Resveratrol ; Male ; Liver/pathology* ; Rats, Sprague-Dawley ; Rats ; Hindlimb Suspension ; Oxidative Stress/drug effects* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Stilbenes/pharmacology* ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis/drug effects*

The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs. MERT's excellent specificity, ultrahigh ligand density, and potential synergistic recognition ability enable it to target the different key regions of ADCs to overcome the deficiencies of traditional technologies. The binding capacity of MERT for antibodies is ten to hundred times higher than that of the mono-epitope or Fc-specific affinity technologies. Since MERT can efficiently capture target ADCs from serum, a novel bioanalytical platform based on MERT and RPLC‒QTOF-MS has been developed to monitor the dynamic changes of ADCs in serum, including the fast changes of drug-to-antibody ratio from 3.67 to 0.22, the loss of payloads (maytansinol), and the unexpected hydrolysis of the succinimide ring of the linker, which will contribute to clarify the fate of ADCs and provide a theoretical basis for future design. In summary, the MERT-based versatile platform will open a new avenue for in-depth studies of ADCs in biological fluids.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective:To evaluate the cervical elasticity in pregnant women with singleton pregnancies exhibiting symptoms of threatened preterm labor using E-cervix elastography, and provide a basis for assessing the risk of preterm birth.Methods:This prospective cohort study included pregnant women with singleton pregnancies between 20 +0 and 32 +6 weeks of gestation and no history of preterm birth who developed symptoms of threatened preterm labor and attended the obstetrics outpatient clinic of the Hunan Provincial Maternal and Child Health Care Hospital from May 2022 to May 2023. Several cervical elastography data, including cervical length (CL), hardness ratio (HR), internal ostium (IOS), and external ostium (EOS), were obtained using E-cervix technology, and the differences in these data were compared between women with different pregnancy outcomes (preterm or full-term birth) or different CLs. Statistical analysis was performed using covariance analysis (adjusted for gestational age), Chi-square test or corrected Chi-square test, and Pearson correlation analysis. Results:A total of 120 pregnant women were included, with 39 (32.5%) in the preterm group and 81 (67.5%) in the full-term group. There were 41 women (34.2%) with CL≤25 mm and 79 (65.8%) with CL>25 mm. Among the 41 women with CL≤25 mm, 26 had preterm birth and 15 delivered at term. Compared with the full-term group, the preterm group had a lower cervical HR [(35.75±8.94)% vs. (61.30±10.69)%, F=156.88], but higher IOS and EOS (0.47±0.13 vs. 0.31±0.09, F=54.99; 0.45±0.11 vs. 0.34±0.08, F=34.57) (all P<0.001). The patients with CL≤25 mm had a lower cervical HR [(43.17±14.32)% vs. (58.09±13.94)%, F=26.03], but higher IOS and EOS (0.46±0.14 vs. 0.32±0.08, F=38.71; 0.44±0.12 vs.0.34±0.08, F=21.36) as compared with those with CL>25 mm, with all differences being statistically significant (all P<0.001). Among the women with CL≤25 mm, preterm birth cases had lower cervical HR but higher IOS and EOS than those delivered at term (all P<0.001). In both CL≤25 mm and CL>25 mm groups, the preterm birth rate was higher in patients with HR<50% than in those with HR≥50% [95.5% (21/22) vs. 5/19, χ2=21.01, P<0.001; 61.9% (13/21) vs. 0.0% (0/58), corrected χ2=38.59, P<0.001]. Besides, an increased preterm birth rate was also observed in patients with HR<40% as compared with those with HR≥40% regardless of the CL [CL≤25 mm: 18/18 vs. 34.8% (8/23), χ2=18.51, P<0.001; CL>25 mm: 11/14 vs. 3.1% (2/65), corrected χ2=42.42, P<0.001]. Pearson correlation analysis showed that there was a significant positive correlation between CL and HR ( r=0.51, P<0.001). Conclusion:E-cervix elastography can quantify the hardness of cervical tissue, and identify truly "soft" cervices that are associated with high risk of preterm birth, showing great potential as a more efficient new technology for predicting preterm birth.

Dynamic tracking analysis of monoclonal antibodies(mAbs)biotransformation in vivo is crucial,as certain modifications could inactivate the protein and reduce drug efficacy.However,a particular chal-lenge(i.e.immune recognition deficiencies)in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen.To address this limitation,a multi-epitope affinity technology utilizing the metal organic framework(MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region(CDR)mimotope peptide(HH24)and non-CDR mimotope aptamer(CH1S-6T)onto the surface of MOF@Au nanocomposite.Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited signifi-cantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope af-finity technology.Moreover,the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry(LC-QTOF-MS).Therefore,multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb.Particularly,the novel bioanalytical platform can be suc-cessfully used for the tracking analysis of trastuzumab modifications in different biological fluids.Compared to the spiked phosphate buffer(PB)model,faster modification trends were monitored in the spiked serum and patients'sera due to the catalytic effect of plasma proteins and relevant proteases.Differences in peptide modification levels of trastuzumab in patients'sera were also monitored.In summary,the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb,contributing to improved understanding and paving the way for future research and clinical applications.