1.Study on the role and mechanism of SPP1+ macrophages in the formation of chronic renal allograft fibrosis
Zexin YANG ; Zeping GUI ; Junqi ZHANG ; Gang ZHANG ; Hao CHEN ; Li SUN ; Shuang FEI ; Min GU ; Zijie WANG
Organ Transplantation 2026;17(3):413-421
Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)+ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1+ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1+ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1+ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1+ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1+ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.
2.Carbon ion radiotherapy planning: a study of prescription dose conversion between microdosimetric kinetic model and local effect model
Zijie ZUO ; Zhiqiang LIU ; Qinghua ZHANG ; Xu HAN ; Tianqi DU ; Hongtao LUO ; Shilong SUN ; Yu ZHANG ; Qiuning ZHANG ; Xiaohu WANG
Chinese Journal of Radiation Oncology 2025;34(2):151-159
Objective:In carbon ion treatment planning of water phantom, establish a conversion factor calculation system and conversion factor curves for organs at risk (OAR) for microdosimetric kinetic models (MKM) and local effect models (LEM), and validate them in clinical patient planning.Methods:Using a uniform spherical water phantom as the research object, relative biological effectiveness-weighted doses (RWD) for the LEM were re-calculated based on the physical dose of RayStation-MKM. The median dose within the planning target volume (PTV) of LEM and MKM was regarded as the conversion factor. The impacts of single-fraction target prescription dose, spread-out Bragg peak (SOBP) width and depth, shape, and irradiation mode on the conversion factor were assessed, and a conversion factor calculation system was established. Additionally, the accuracy of the conversion factor calculation system was validated using both water phantoms and clinical patient cases. The conversion factor curves for OAR were computed based on clinical patient treatment plans.Results:The primary influencing factors for the conversion factors were the single-fraction prescription dose, target SOBP width and depth. The conversion factors were increased with the increase of SOBP width and target depth, whereas decreased with the increase of the single-fraction prescription dose. Under single-field irradiation, a conversion factor calculation system was established based on above 3 parameters. For the plans of 9 patients, the average difference between the calculated results and the conversion factor calculation system was 0.340% ± 0.203%, and the average difference in the conversion curves for OAR was 2.650% ± 2.399%.Conclusion:A dose conversion factor calculation system and conversion factor curves for OAR for carbon ion radiotherapy are established for MKM and LEM, and their accuracy meets the requirements for use in clinical patient treatment plans.
3.Carbon ion radiotherapy planning: a study of prescription dose conversion between microdosimetric kinetic model and local effect model
Zijie ZUO ; Zhiqiang LIU ; Qinghua ZHANG ; Xu HAN ; Tianqi DU ; Hongtao LUO ; Shilong SUN ; Yu ZHANG ; Qiuning ZHANG ; Xiaohu WANG
Chinese Journal of Radiation Oncology 2025;34(2):151-159
Objective:In carbon ion treatment planning of water phantom, establish a conversion factor calculation system and conversion factor curves for organs at risk (OAR) for microdosimetric kinetic models (MKM) and local effect models (LEM), and validate them in clinical patient planning.Methods:Using a uniform spherical water phantom as the research object, relative biological effectiveness-weighted doses (RWD) for the LEM were re-calculated based on the physical dose of RayStation-MKM. The median dose within the planning target volume (PTV) of LEM and MKM was regarded as the conversion factor. The impacts of single-fraction target prescription dose, spread-out Bragg peak (SOBP) width and depth, shape, and irradiation mode on the conversion factor were assessed, and a conversion factor calculation system was established. Additionally, the accuracy of the conversion factor calculation system was validated using both water phantoms and clinical patient cases. The conversion factor curves for OAR were computed based on clinical patient treatment plans.Results:The primary influencing factors for the conversion factors were the single-fraction prescription dose, target SOBP width and depth. The conversion factors were increased with the increase of SOBP width and target depth, whereas decreased with the increase of the single-fraction prescription dose. Under single-field irradiation, a conversion factor calculation system was established based on above 3 parameters. For the plans of 9 patients, the average difference between the calculated results and the conversion factor calculation system was 0.340% ± 0.203%, and the average difference in the conversion curves for OAR was 2.650% ± 2.399%.Conclusion:A dose conversion factor calculation system and conversion factor curves for OAR for carbon ion radiotherapy are established for MKM and LEM, and their accuracy meets the requirements for use in clinical patient treatment plans.
4.Establishment and application of medical performance evaluation index system for clinicians competing for senior professional titles in cancer hospitals
Xin ZHANG ; Zijie SHAO ; Zongyan YING ; Juda CHEN ; Wei WEI ; Zhuowei LIU ; Ying SUN ; Feng ZHOU
Modern Hospital 2024;24(11):1738-1741
Following the reform of the professional title system for"Breaking Four One-sided Evaluation Criteria"—focu-sing on more than just papers,titles,academic qualifications,and awards-establishing a scientific,systematic,and comprehen-sive medical performance evaluation index system has become essential for developing medical talent teams and conducting profes-sional title assessments fundamentally.This study establishes a medical performance evaluation index system tailored for clinicians in various departments of a cancer hospital who are competing for senior professional titles.This system comprises six primary in-dicators and 18 secondary indicators,with results presented in a ranked format of medical performance.Additionally,we have al-so analyzed the corr-elation between clinicians'medical performance rankings and their professional title evaluation outcomes through practical application.The results indicate that clinicians with higher performance rankings have significantly higher suc-cess rates in evaluations(P<0.05).This index system underscores clinical practice,enhances classification-based evaluations,and supports advanced information management and precision in hospital administration,thereby providing a solid foundation for strengthening the hospital's core competitiveness.
5.Development and Challenges of Additive Manufactured Customized Implant
Changning SUN ; Zijie MENG ; Ling WANG ; Jiankang HE ; Qin LIAN ; Lin GAO ; Xiao LI ; Mao MAO ; Hui ZHU ; Dichen LI
Chinese Journal of Medical Instrumentation 2024;48(3):237-244
Additive manufacturing(3D printing)technology aligns with the direction of precision and customization in future medicine,presenting a significant opportunity for innovative development in high-end medical devices.Currently,research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants.Primary areas including metallic orthopaedic implants,polyether-ether-ketone(PEEK)bone implants,and biodegradable implants have been developed for clinical and industrial application.Recent research achievements in these areas are reviewed,with a discussion on the additive manufacturing technologies and applications for customized implants.Challenges faced by different types of implants are analyzed from technological,application,and regulatory perspectives.Furthermore,prospects and suggestions for future development are outlined.
6.Evaluation of left ventricular structural and functional abnormalities and vascular calcification in kidney transplant recipients and the effect of bone metabolism on them
Li SUN ; Zhijian HAN ; Xiaobing JU ; Jun TAO ; Hao CHEN ; Zhengkai HUANG ; Zijie WANG ; Shuang FEI ; Min GU ; Ruoyun TAN
Chinese Journal of Organ Transplantation 2023;44(4):214-222
Objective:To evaluate left ventricular structural and functional abnormalities and vascular calcification in kidney transplant (KT) recipients, explore their influencing factors and examine the effects of mineral and bone disorders.Methods:From January 2017 to December 2019, retrospective analysis was performed for 292 KT recipients. Biochemical markers of bone metabolism, bone mineral density (BMD), left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), left ventricular diastolic function, coronary artery calcification (CAC) score and thoracic aortic calcification (TAC) score were assessed. Linear regression and binary Logistic regression analyses were employed for evaluating the influencing factors of cardiovascular parameters and the influence of abnormal mineral and bone metabolism.Results:Postoperative abnormalities in mineral and bone disorders were manifested mostly as hypercalcemia (8.9%, 26/292), hypophosphatemia (27.1%, 79/292), low 25-hydroxyvitamin D (25(OH)vitD) (67.0%, 196/292), hyperparathyroidismhigh parathyroid hormone (PTH) (50.6%, 148/292), elevated bone turnover markers and bone loss rate of 25%-30%. The prevalence of LVH, LVEF<50%, left ventricular diastolic dysfunction, high CAC score and high TAC score were 39.9%(116/292), 0%, 13.1%(38/292), 17.3%(50/292) and 39.9%(116/292) respectively. The results of multivariate analysis indicated that LVH was correlated positively with hypertension and serum calcium (Ca) (95% CI: 1.242-28.080, P=0.026; 95% CI: 1.714-277.584, P=0.018); LVEF was correlated positively with lumbar vertebrae BMD (95% CI: 0.000 1-0.005 5, P=0.041); Left ventricular diastolic dysfunction was correlated positively with age, diabetes and parathyroid hyperplasia/nodules (95% CI: 1.050-1.176, P<0.001; 95% CI: 2.118-43.813, P=0.003 and 95% CI: 1.419-9.103, P=0.007); High CAC score was correlated positively with recipient age and dialysis time (95% CI: 1.036-1.160, P=0.001; 95% CI: 1.009-1.041, P=0.002); High TAC score was correlated positively with age (95% CI: 1.095-1.215, P<0.001). Correlation analysis indicated that TAC was correlated positively with serum Ca ( r=0.233, P=0.003), bone-specific alkaline phosphatase (BALP)( r=0.325, P<0.001) and type Ⅰ collagen cross-linked N-terminal peptide (NTX)( r=0.204, P=0.011) and negatively with femoral neck BMD ( r=0.194, P=0.017). Conclusions:There is a high prevalence of left ventricular structural and functional abnormalities and vascular calcification. It is closely correlated with mineral and bone disorders.
7.Retrospective study of a novel anti-rheumatic drugs to reduce the panel reactive antibody of kidney transplant recipients
Hao CHEN ; Min GU ; Zhengkai HUANG ; Dengyuan FENG ; Li SUN ; Zijie WANG ; Shuang FEI ; Jun TAO ; Ruoyun TAN ; Xiaobing JU ; Zhijian HAN
Chinese Journal of Organ Transplantation 2020;41(3):163-168
Objective:To observe the efficacy and safety of Iguratimod in reducing the level of panel reactive antibodies in renal transplant recipients.Methods:The clinical data of 35 patients with PRA-positive renal transplant recipients were retrospectively analyzed. All recipients were treated with Iguratimod for PRA-positive. The changes in PRA levels before and after treatment and the adverse events were observed.Results:Of the 35 recipients, 4 of them were discontinued due to pulmonary infection, and 2 patients were discontinued during the observation period. 3 patients were lost to follow-up. A total of 26 recipients were included. When Iguratimod was taken to 9 months, the PRA was reviewed. 71.5 % of the 207 sites showed a downward trend, 69.9 % of the 107 class I sites and 75.9 % of the 41 class II site showed a downward trend, and there was no difference in renal function before and after treatment. There were no significant changes in blood routine, liver function, blood lipids, and blood glucose. There were no other adverse events.Conclusions:Iguratimod can effectively reduce the level of PRA in renal transplant recipients with less adverse events.
8.Prognosis of chronic active antibody-mediated rejection in kidney transplantation
Li SUN ; Zhijian HAN ; Xiaobing JU ; Jun TAO ; Hao CHEN ; Zhengkai HUANG ; Zijie WANG ; Shuang FEI ; Min GU ; Ruoyun TAN
Chinese Journal of Organ Transplantation 2020;41(3):169-173
Objective:To evaluate the values of bone mineral density(BMD)of renal transplant recipients and analyze the influencing factors so as to provide rationales for preventing and treating osteoporosis after renal transplantation.Methods:A retrospective study was conducted for clinical data of 254 renal transplant recipients hospitalized from January 2017 to May 2019. The values of BMD of right femoral neck and lumbar vertebrae were detected by dual-energy X-ray absorptiometry(DEXA)and their relationships with other clinical parameters analyzed.Results:The average age was(40.5±9.8)years. Males accounted for 66.1 %, and menopausal women 5.9 %. The prevalence of osteopenia/osteoporosis of right femoral neck bone mass and lumbar vertebrae was 20.1 %, 2.8 % and 26.1 %, 3.6 % respectively. Chi-square test showed that recipients with lower BMD of femoral neck and lumbar spine were elders, menopausal women and those with longer postoperative time( P<0.05). Multivariate linear regression analysis indicated that BMD of right femoral neck was positively correlated with BMI and negatively correlated with acute rejection( P<0.05). The BMD of lumbar vertebrae was positively correlated with BMI and negatively correlated with PTH level ( P<0.05). Conclusions:There is a high prevalence of bone loss in kidney transplant recipients. Regular monitoring of BMD, active control of hyperparathyroidism, maintaining an excellent nutritional status, tapering of glucocorticoid dose and using immunosuppressants with less effect on bone metabolism may prevent osteoporosis.
9.Quadruple low-dose immunosuppressant maintenance therapy protocol in renal transplanted recipients within three months after renal transplantation
Shuang FEI ; Zijie WANG ; Hao CHEN ; Li SUN ; Jun TAO ; Zhijian HAN ; Ruoyun TAN ; Min GU ; Xiaobing JU
Chinese Journal of Organ Transplantation 2020;41(3):174-179
Objective:To observe the efficacy and safety of quadruple low-dose immunosuppressant maintenance therapy of sirolimus(SRL), calcineurin inhibitors(CNIs), mycophenolate mofetil(MMF)and glucocorticoid in recipients switched within three months after renal transplantation.Methods:This retrospective study recruited 61 recipients on quadruple immunosuppressive therapy within three months after renal transplantation from 2013 to 2018. The changes of serum creatinine(SCr), blood urea nitrogen(BUN), hemoglobin(HGB), white blood cell(WBC), platelet(PLT), liver function, fasting blood-glucose(FBG), serum lipid, electrolyte and urine protein before and after using this protocol were recorded.Results:No significant difference existed between before and after protocol switching in WBC or serum sodium. But after protocol switching, significant differences could be observed in SCr, BUN, serum calcium, serum potassium, aspartate transaminase(AST), PLT, alanine transaminase(ALT), HGB, FBG, triglycerides(TG)and cholesterol(TC, P<0.05). Urine protein negative rate was 44.26 % before switching. However, it was 81.97 % after protocol switching. After switching during a 1-year follow-up period, the incidence of pulmonary infection rate was 24.59 %, the incidence of BKV infection rate 4.92 %, the incidence of transplant renal artery stenosis 3.28 % and the incidence of acute rejection 6.56 %. Conclusions:Quadruple low-dose immunosuppression maintenance therapy of SRL, CNIs, MMF and glucocorticoid switched within 3 months after renal transplantation may be an effective and safe protocol of improving renal allograft function and enhancing recipient prognosis.
10.Detection of proximal serrated polyps:a single-center retrospective analysis
Qingyun LI ; Peng XIAO ; Tingsheng LING ; Yangyang SUN ; Lijun LUO ; Rong LIANG ; Zijie DENG ; Waikay SETO
Chinese Journal of Digestive Endoscopy 2019;36(2):86-90
Objective To investigate the prevalence and endoscopic detection rate of proximal serrated polyps and to screen the risk factors. Methods The data of 9010 colonoscopies performed by 22 endoscopists between September 2016 and September 2017 were reviewed. The adenoma detection rate (ADR) and proximal serrated polyp detection rate (PSDR) were calculated, and the correlation between ADR and PSDR was estimated by Pearson correlation coefficients. Multivariate logistic regression was used to analyze PSDR among endoscopists. Results For all subjects, the mean ADR was 30. 07% ( ranged from 20. 00% to 40. 78%) and mean PSDR was 4. 70% ( ranged from 1. 52% to 9. 28%) . PSDR of males was 1. 38 times of that of females ( OR=1. 38, 95%CI:1. 13-1. 69, P<0. 01) . For 3560 cases ( 39. 51%) of 50 years and older subjects, the mean ADR was 45. 01% ( 28. 99%-57. 78%) and mean PSDR was 6. 08%(2. 07%-10. 56%). PSDR was moderately correlated with ADR (r=0. 48, P=0. 02). PSDR of males was 1. 36 times of that of females (OR=1. 36, 95%CI: 1. 04-1. 80, P=0. 03). Endoscopist was a significant risk factor for detection of proximal serrated polyps ( P<0. 01) . Compared with endoscopist with the highest PSDR, odds ratio of other endoscopists ranged from 0. 16 (95%CI:0. 06-0. 40, P<0. 01) to 0. 83 (95%CI:0. 53-1. 32, P=0. 44) . Conclusion Proximal serrated polyps are more common in males, who are over 50 years old. The PSDR is highly variable and dependent on endoscopists. It is possible that a certain proportion of proximal serrated polyps are missed during colonoscopy.

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