1.Research Progress on the Role of Programmed Cell Death in Flap Ischemia-Reperfusion Injury
Jiwei ZHANG ; Jie ZHANG ; Xinshan WANG ; Xingzhang YAO ; Zhenxing JIANG ; Zhijun HE ; Tao LIU ; Jianliang LI ; Hui YAO ; Jie AN ; Qiuyue ZHAO ; Xiaotao WEI ; M Rayan GHAZI
Medical Journal of Peking Union Medical College Hospital 2026;17(3):851-861
Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.
2.Impact of tumor treating fields transducer arrays on concurrent radiotherapy dosimetry
Keqiang WANG ; Jie CHEN ; Jianbo JIAN ; Peng WANG ; Xinshan ZHANG ; Hongyang ZHANG ; Wenxue ZHANG
Chinese Journal of Radiation Oncology 2024;33(5):438-445
Objective:To investigate the dosimetric impact of tumor treating fields (TTF) transducer arrays on concurrent radiotherapy for patients with glioblastoma (GBM).Methods:A strategy was developed to accurately simulate the dosimetric impact of TTF arrays on radiotherapy, including the establishment of accurate auto-segmentation technique for TTF arrays, determination of the relative electron density (RED) of the transducer arrays and validation of the dose calculation accuracy in the treatment planning system (TPS) for TTF arrays. Based on this strategy, the dosimetric impact of TTF arrays on clinical treatment plans of 10 patients with GBM was evaluated. Furthermore, the dosimetric comparison between the clinical plans with different beam energies were investigated when TTF arrays were used. The methods of analysis of variance were paired t-test or Wilcoxon signed-rank test based on whether the differences followed a normal distribution. Results:The auto-segmentation technique for TTF arrays was established by designing a workflow in Mim software and achieved a Dice coefficient of 0.93 and a Jaccard index of 0.87 compared to the standard contours. The RED of TTF arrays was 3.3 which was derived from the comparison between the measured and simulated percentage depth dose (PDD) with and without TTF arrays on phantom. Measured and calculated dose distributions were compared using the 2D gamma analysis. The gamma passing rates on the coronal plane of 4 mm and 5.1 cm depth were 96.64% and 94.55% at the criteria of 3% /3 mm, indicating that the calculation accuracy of algorithm in TPS for TTF arrays could meet clinical requirements. In the clinical treatment plans of patients with GBM, the presence of TTF arrays caused a mean reduction of planning target volume (PTV) dose of approximately 1%, and an increase in scalp dose of approximately 5%, with minimal impact on other organs at risk (OAR). The 10 MV plans resulted in a higher dose of PTV by 0.3% and lower dose of scalp by approximately 3% compared to the 6 MV plans, when considering TTF arrays.Conclusions:The accurate simulation strategy for the dosimetric impact of TTF arrays on radiotherapy established in this study ensures the accuracy and precision of the calculations. In TTF therapy combined with concurrent radiotherapy for GBM, TTF arrays have slight effect on PTV dose, but significantly increase scalp dose. High-energy beam can reduce the impact of TTF arrays.
3.Plan quality comparison between coplanar and non-coplanar VMAT for the whole brain radiotherapy with hippocampus and hypothalamic-pituitary axis sparing
Keqiang WANG ; Jie CHEN ; Jianbo JIAN ; Peng WANG ; Xinshan ZHANG ; Hongyang ZHANG ; Wenxue ZHANG
Chinese Journal of Radiation Oncology 2024;33(7):634-641
Objective:To compare the plan quality between coplanar and non-coplanar volumetric modulated arc therapy (co-VMAT and nco-VMAT) techniques for the whole brain radiotherapy with hippocampus and hypothalamic-pituitary (HT-P) axis sparing.Methods:A total of 15 patients who underwent prophylactic cranial irradiation in Tianjin Medical University General Hospital from November 2021 to August 2023 were retrospectively selected. The hippocampus and HT-P axis were delineated according to Radiation Therapy Oncology Group (RTOG) 0933 and contouring guidelines for hypothalamus. Co-VMAT and nco-VMAT plans were generated for each patient with a prescription dose of 30 Gy in 10 fractions. Then, dosimetric parameters, plan robustness, plan complexity, and delivery efficiency for both plans were compared using paired t-test. Results:Both co-VMAT and nco-VMAT plans could achieve dosimetric objectives. There were no significant differences in D 2%, D 95% and conformity index (CI) of planning target volume (PTV) between the two plans. The D 98% and homogeneity index (HI) of PTV in co-VMAT showed a slight inferiority compared to that in nco-VMAT (D 98%: 26.37 Gy vs. 26.96 Gy, P=0.001; HI: 0.25 vs. 0.24, P=0.002). The D min of bilateral hippocampus in co-VMAT were 8.55 Gy (left) and 8.32 Gy (right), which were lower than 9.31 Gy (left) and 9.26 Gy (right) in nco-VMAT. In addition, the D mean of the hypothalamus and pituitary in the co-VMAT plan were lower than those in the nco-VMAT plan (hypothalamus: 11.54 Gy vs. 12.27 Gy; pituitary: 11.72 Gy vs.12.1 Gy, both P<0.001). The doses to the hippocampus and HT-P axis were highly sensitive to errors in both co-VMAT and nco-VMAT plans, while the sensitivity of dose to errors in the PTV and other organs at risk was low. The co-VMAT plan had lower complexity compared to the nco-VMAT plan, with γ passing rate at 3%/3 mm criteria of 99.06%±0.60% and 98.05%±2.89%, respectively. The average beam-on time of the co-VMAT plan was 4.8 min, approximately 2/3 of the time for nco-VMAT, while the average treatment time was 6.3 min, approximately half of the treatment time for nco-VMAT. Conclusions:Both co-VMAT and nco-VMAT can achieve hippocampus and HT-P axis sparing in the whole brain radiotherapy. In the co-VMAT plan, the D 98% of the PTV is slightly smaller, but it provides better protection for the hippocampus and HT-P axis. The doses to the hippocampus and HT-P axis are sensitive to errors in both plans. However, the co-VMAT plan has lower complexity, higher delivery efficiency, and is more suitable for clinical treatment.
4.Correlation Between Deep Brain White Matter Ischemia and MR Diffusion Tensor Imaging of Mild Cognitive Impairment
Licun LEI ; Yaqiang DU ; Li HE ; Weixiu WANG ; Yanhua WU ; Xinshan GUO
Chinese Journal of Medical Imaging 2013;(10):737-740
Purpose To investigate the correlation between the brain white matter changes of MR diffusion tensor imaging (DTI) and cognitive function in the patients with mild cognitive impairment. Materials and Methods The patients (40 cases) were classified into two groups:group A (20 patients with ischemic foci in the deep white matter ) and group B (20 patients without ischemic foci in the deep white matter), and 20 normal controls was enrolled. Conventional MRI, DTI, mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) were applied, then fractional anisotropy (FA) value and apparent diffusion coefficient (ADC) value were compared among three groups. The scores of MoCA was analyzed between the patient groups. Results The decreased FA value, increased ADC value and decreased MoCA scores was demonstrate in group A, and showed significant difference compared with group B (t=-4.229,-3.251,-7.533,-2.702,-2.660;P<0.05). The increased ADC value and decreased FA value in the frontal and hippocampus region were detected in group B compared with normal controls (t=-7.790,-2.785,-4.415,-5.164;P<0.05). Conclusion The early and special structural changes can be detected using DTI compared with conventional MRI. The severe white matter lesions can be demonstrated in the patients with ischemic foci in the deep white matter, who is prone to dementia.
5.Quantity Evaluation and Its Stimulative Role in the Promotion of the Employees
Dinglu WANG ; Jianying LIU ; Li LIU ; Xinshan CHEN
Chinese Journal of Medical Education Research 2002;0(01):-
Quantity evaluation is one of inspiring means, whose essence is to put into practice the effective external stimulation for inner motivation.Its purpose is to inspire potential, to bring all people's best into full play and to raise the performance of employees. The process of quantity evaluation is also the process of developing employee's potential.Besides quantity evaluation is good for judgement and examination of the title of technical post, in favor of outstanding personnel shaping, optimization and collocation of human resources. This will make personnel management work more scientific and standardized.
6.Immunohistochemical study of endothelin in early acute myocardial ischemia in rats
Zhiyong WANG ; Zheng LI ; Xinshan CHEN ;
Chinese Journal of Forensic Medicine 1988;0(04):-
Objective Study the expression of endothelin(ET) of ischaemic myocardium in rat. Method Sixty Wistar rats were randomly divided into 5 groups: coronary artery simply-ligated group,drug-pre-treated group(Isoproterenol,Pituitrin),coronary atherosclerotic group,sham-operated group(as control group). The samples were cut at 15min,30min,45min,60min,90min,120min after coronary (left anterior descending) ligation, and stained with HE and strept avidin-biotin enzyme complex(SABC)method. Results The expression of endothelin was observed with light microscope. Ischaemic myocardium showed ET-positive staining at the early stage of acute myocardial ischaemia in different groups and more in the pre-treated group. Conclusion the SABC-ET method may provide a new marker for diagnosing early myocardial ischaemia, which will be helpful in confirming the cause of sudden coronary death(SCD).
7.EXPRESSION OF ABCG2 TRANSPORTER DURING TRACHEAL REGENERATION IN RATS
Linlin WANG ; Lanling JAI ; Xinshan JIA
Acta Anatomica Sinica 1954;0(02):-
Objective To explore the dynamic changes of tracheal stem cells during tracheal regeneration after injury induced by fluorouracil(5-FU) in rats. Methods Extracorporeal tracheal injury(Wistar rats) was induced by 5-FU.ABCG2 expression in tracheal epithelium during the process of regeneration was analyzed by indirect immunofluorescence and Western blotting. Results 1.After treatment with 5-FU for 12 hours,the tracheal epithelium shed and there were ABCG2 positive cells among residual cells in G-0.Three hours after the removal of 5-FU,the tracheal rings were covered with flattened epithelial cells. ABCG2 positive cells increased slightly.Six-nine hours after the removal of 5FU,the epithelial cells changed into cuboidal,correspondingly,the ABCG2 positive cells increased obviously;At 24 hours after the removal of 5-FU,most of the epithelial cells were cuboidal and merged into pieces,but the ABCG2 positive cells decreased obviously;Until 48 hours after the removal of 5-FU,only a few positive cells could be seen with the pseudostratified mucociliary epithelium restored similar to its original mode.There were no detectable ABCG2 positive cells in normal tracheal epithelium.2.Western blotting analysis showed that there were different ABCG2 levels at different times after the removal of 5-FU which in accordance with the change of immunofluorescene.ABCG2 was minimally detected after treatment with 5-FU for 12 hours,reaching a maximal level at 6 hours after the removal of 5-FU,and then decreased over time.Until 48 hours after the removal of 5-FU,very low ABCG2 level was detected.Conclusion The expression of ABCG2 is correlated to the number of tracheal stem cells,suggesting that ABCG2 may serve as a marker for isolating stem cells from tracheal epithelium.

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