1.Expert consensus on the prevention and treatment of radiochemotherapy-induced oral mucositis.
Juan XIA ; Xiaoan TAO ; Qinchao HU ; Wei LUO ; Xiuzhen TONG ; Gang ZHOU ; Hongmei ZHOU ; Hong HUA ; Guoyao TANG ; Tong WU ; Qianming CHEN ; Yuan FAN ; Xiaobing GUAN ; Hongwei LIU ; Chaosu HU ; Yongmei ZHOU ; Xuemin SHEN ; Lan WU ; Xin ZENG ; Qing LIU ; Renchuan TAO ; Yuan HE ; Yang CAI ; Wenmei WANG ; Ying ZHANG ; Yingfang WU ; Minhai NIE ; Xin JIN ; Xiufeng WEI ; Yongzhan NIE ; Changqing YUAN ; Bin CHENG
International Journal of Oral Science 2025;17(1):54-54
Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans
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Chemoradiotherapy/adverse effects*
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Consensus
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Risk Factors
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Stomatitis/etiology*
2.Therapeutic efficacy of intravenous immunoglobulin in ulcerative colitis
Qian LONG ; Zongkui WANG ; Changqing LI ; Rong ZHANG
Chinese Journal of Blood Transfusion 2025;38(4):522-530
[Objective] To explore the therapeutic effects of intravenous immunoglobulin (IVIG) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). [Methods] C57BL/6 mice were randomly assigned to the control group, the DSS group (model) and the DSS+IVIG group (treatment). The DSS group and the DSS+IVIG group received 3% DSS in drinking water to establish the acute UC mouse model. During the experiment, the DSS+IVIG group received IVIG (1 g/kg/2d) via tail vein injection, while the DSS group received equivalent saline via tail vein injection at the same dose and frequency. The symptoms of the mice were observed, body weight changes were recorded, and the disease activity index (DAI) was calculated daily. At the end of the experiment, hematoxylin-eosin (HE) staining was used to observe the pathological changes and inflammatory cell infiltration of colon tissue; Periodic acid-Schiff (PAS) staining was used to quantify the number of goblet cells; Luminex was used to detect the levels of inflammatory-related cytokines (such as TNF-α, IL-6 and MMPs) in colon; western blot and qRT-PCR were respectively used to detect the protein expression and mRNA levels of tight junction proteins (ZO-1, Occludin, Claudin-3). [Results] DSS induced weight loss, diarrhea, bloody stool, increased DAI score, and shortened colon length in mice. Compared with DSS group, after the administration of IVIG, the DAI score was significantly reduced (P<0.001), colon length was increased (P<0.001), infiltration of inflammatory cells and pathological damage were alleviated in colonic mucosa (P<0.001), the number of goblet cells were increased (P<0.05), and the levels of inflammatory-related cytokines TNF-α, IL-6, IL-6R, MMP2, MMP3 and Chitinase3like1 were decreased (all P<0.05). Western blot and qRT - PCR results showed that IVIG significantly up-regulated the protein expression of ZO-1, Occludin and claudin-3 (all P<0.05) and the mRNA levels of ZO-1 and Occludin (all P<0.05). [Conclusion] IVIG has protective effects on colitis by inhibiting the pathological release of inflammatory-related cytokines such as TNF-α, IL-6 and MMPs and restoring the integrity of intestinal barrier.
3.Basic connotation, times requirement, and cultivating path of “benevolent doctors” in the new era
Jiguang ZONG ; Ying WANG ; Mingjuan YUAN ; Cong LI ; Changqing ZOU
Chinese Medical Ethics 2025;38(3):328-335
Promoting the construction of a “Healthy China” is essential to building a great modern socialist country. Health workers in every era have their historical missions and they are the “benevolent doctors” of their own era. Therefore, clarifying the basic connotation and times requirements of “benevolent doctors” has become the first question to be answered in cultivating “benevolent doctors”. The basic connotation of “benevolent doctor” should reflect not only the comprehensive development of moral, intellectual, physical, aesthetic, and labor education in fostering virtue and nurturing talents, but also embody the people-centered development philosophy, promote social equity and justice, and reflect the strategic needs of building a “Healthy China.” Specifically in the practice of medical education, emphasizing both medical science spirit and medical humanities spirit has become an important path to cultivate “benevolent doctors” in the new era.
4.Analysis of Differences in Secondary Metabolites Between Dendrobium nobile Bionic Wild Cultivated on Epiphytic Stones and Trees Based on Widely Targeted Metabolomics
Yifan SHI ; Changqing ZHOU ; Jiaojiao WANG ; Lin CHEN ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):218-224
ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees, so as to elucidate the scientific connotation of "only those that grow on stones has superior quality", and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry(UPLC-QTRAP-MS/MS)-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis(PCA), hierarchical cluster analysis(HCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection(VIP) value≥1 and log2fold change(FC)≥1 or ≤-1, and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes, dominated by flavonoids(292), phenolic acids(284), and alkaloids(189). Through OPLS-DA screening, 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile, epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids, phenolic acids, alkaloids, lignans and coumarins, while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids, and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis, flavonoid biosynthesis, tyrosine metabolism, and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids, flavonoids, and alkaloids in D. nobile, indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis, and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.
5.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
6.Anti-atherosclerosis Effect and Mechanism of Siegesbeckiae Herba Water Decoction via Regulation of NF-κB Signaling Pathway
Tengyue WANG ; Mingyue ZHAO ; Xiaonan YUE ; Yuan CHEN ; Changqing LU ; Huan WANG ; Kaifang FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):106-114
ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction (SWD) at different doses on atherosclerosis (AS) in a mouse model induced by a high-fat diet and analyze its potential mechanism of action. MethodsThirty-six male ApoE-/- mice were randomly divided into six groups: blank control group, model group, low-dose, medium-dose, and high-dose SWD groups, and positive control group. Firstly, the AS mouse model was created by feeding mice a high-fat diet. After successful modeling, the low-, medium-, and high-dose SWD groups were intragastrically administered with SWD at 0.65, 1.3, 2.6 g·kg-1, respectively. The positive control group was intragastrically administered with 30 mg·kg-1 of atorvastatin calcium aqueous solution, while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage, all administered for 12 weeks. During the administration period, the general condition of the mice was observed and recorded daily. Before sampling, color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in aortic tissue in mice, and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum lipid indices and the levels of interleukins (IL-1β, IL-4, IL-6, and IL-10) and tumor necrosis factor-α (TNF-α) in mice. Protein expression levels of IKKα, IKKβ, and NF-κB p65 in mouse aortic tissue were detected by Western blot. ResultsCompared with the blank control group, the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo, suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation, fibrous connective tissue proliferation, and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue (P<0.01). ELISA results indicated significantly elevated levels of IL-1β, IL-6, TNF-α, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) in mouse serum (P<0.01), as well as significantly decreased levels of IL-4, IL-10, and high-density lipoprotein (HDL) (P<0.01). Western blot results showed that the expression of IKKα, IKKβ, and NF-κB p65 in mouse aortic tissue increased significantly (P<0.01). Compared with those in the model group, mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group, the aortic vascular wall echoes were weakened, and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD (P<0.05). In the medium-dose SWD group, serum levels of IL-1β, IL-6, TNF-α, TC, TG, and LDL were significantly decreased (P<0.05, P<0.01), while those of IL-4 and IL-10 were significantly increased (P<0.01). In the high-dose SWD group, levels of IL-1β, IL-6, TNF-α, TC, TG, and LDL were significantly decreased (P<0.01), while IL-4, IL-10, and HDL were significantly increased (P<0.01). The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group (P<0.05), and IKKα, IKKβ, and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups (P<0.05, P<0.01). ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway, thereby reducing inflammation, plaque area, and lipid content in the body.
7.C6TSEDRVAJZ, a combination of small-molecule compounds, induces differentiation of human placental fibroblasts into epithelioid cells in vitro.
Zhenjia DAI ; Qunwei GAO ; Mengjiao YING ; Ao WANG ; Juan HONG ; Chunjing WANG ; Yu GUO ; Changqing LIU ; Gaofeng LIU
Journal of Southern Medical University 2025;45(2):322-330
OBJECTIVES:
To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds.
METHODS:
HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O2), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated.
RESULTS:
Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%.
CONCLUSIONS
The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans
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Fibroblasts/drug effects*
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Pregnancy
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Female
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Cell Differentiation/drug effects*
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Pyrimidines/pharmacology*
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Placenta/cytology*
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Cells, Cultured
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Pyridines/pharmacology*
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Pyrazoles/pharmacology*
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Epithelial Cells/cytology*
8.Protective effects of butyrate on sepsis-related myocardial dysfunction through ferroptosis inhibition
Shiwei WANG ; Lu LI ; Liangfeng GAO ; Changqing ZHU ; Jianfei XIONG
Chongqing Medicine 2025;54(4):818-823
Objective To investigate the protective effects of butyrate on sepsis-related myocardial dys-function.Methods Thirty healthy 8-week-old male Sprague-Dawley rats were randomly divided into three groups:sham operation group(SH,n=10),sepsis group(CL,n=10),and butyrate group(BU,n=10).The CL and BU groups underwent cecal ligation and puncture(CLP)to establish sepsis models,while the SH group received the same surgical procedure without cecal ligation or puncture.Within 30 minutes post-opera-tion,the SH and CL groups received 5 mL normal saline via gavage,whereas the BU group was administered 5 mL sodium butyrate solution(500 mg/kg)in normal saline.Cardiac output(CO)and ejection fraction(EF)were compared among the three groups.Myocardial histopathological injury was assessed by HE staining,and mitochondrial ultrastructural damage was observed by electron microscopy.Serum levels of brain natriuretic peptide(BNP),cardiac troponin Ⅰ(cTnⅠ),and butyrate were compared among groups.Western blot analysis was performed to detect and compare the expression levels of long-chain acyl-CoA synthetase 4(ACSL4)and glutathione peroxidase 4(GPX4)in myocardial tissues.Results After intervention,the BNP and cTnⅠ levels in the CL group were higher than those in the SH group,while CO and EF were lower than those in the SH group(P<0.05).The BNP and cTnⅠ levels in the BU group were lower than those in the CL group,whereas CO and EF levels were higher than those in the CL group(P<0.05).HE staining of myocardial tissues re-vealed more severe inflammatory cell infiltration and myocardial cell edema in the CL group compared with the SH group,while the BU group showed reduced inflammatory cell infiltration.Mitochondrial membrane in-tegrity was impaired in the CL group manifested by unclear cristae,swelling,vacuolar degeneration and rup-ture,whereas mitochondrial damage was attenuated in the BU group.Serum butyrate levels were measured as(61.7±21.6)μg/mL,(95.3±16.6)μg/mL and(302.2±49.7)μg/mL in the CL,SH and BU groups respec-tively(P<0.05).The ACSL4 expression in the CL group was higher than that in the SH group,while GPX4 protein expression was lower than that in the SH group(P<0.05).The BU group exhibited lower ACSL4 expression and higher GPX4 protein expression compared with the CL group(P<0.05).Conclusion Buty-rate can ameliorate myocardial injury in septic rats,and its protective effect may be associated with the inhibi-tion of myocardial ferroptosis.
9.Predictive value of serum CTSB and NOX4 levels for the prognosis of sepsis related acute kidney injury patients
Naixi JI ; Yunyun CUI ; Wenhao LIU ; Shangzhen LI ; Xiankui WANG ; Changqing YAO
International Journal of Laboratory Medicine 2025;46(18):2207-2211,2218
Objective To investigate prognostic value of serum levels of cathepsin B(CTSB)and NADPH oxidase 4(NOX4)in patients with sepsis associated acute kidney injury(S-AKI).Methods A total of 306 pa-tients with sepsis treated to the hospital from June 2023 to June 2024 were selected,including 192 patients with S-AKI(S-AKI group)and 114 patients without S-AKI(non-S-AKI group).According to the prognosis of S-AKI patients,they were divided into poor prognosis group(n=127)and non-poor prognosis group(n=65).The differences of CTSB and NOX4 in different groups were compared.Pearson analysis was conducted to analyze the correlation between CTSB,NOX4 and clinical indicators.The influencing factors of poor prognosis in S-AKI patients was analyzed according to multivariate Logistic regression.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTSB and NOX4 on the poor prognosis of S-AKI pa-tients.Results Th e serum levels of CTSB,NOX4 and serum creatinine(SCr)in S-AKI group were signifi-cantly higher than those in non-S-AKI group(P<0.05),while the mean arterial pressure and oxygenation in-dex were lower than those in non-S-AKI group(P<0.05).Serum levels of CTSB and NOX4 in patients with sepsis were positively correlated with SCr(P<0.05).Compared to non-poor prognosis group,the age,SCr,CTSB and NOX4 of patients in the poor prognosis group were higher,while the mean arterial pressure and ox-ygenation index were lower(P<0.05).The increased mean arterial pressure and oxygenation index were pro-tective factors for poor prognosis in S-AKI patients(P<0.05),and the increased age,SCr,CTSB and NOX4 levels were risk factors for poor prognosis in S-AKI patients(P<0.05).ROC curve showed that the area un-der the curve(AUC)of CTSB combined with NOX4 was significantly higher than AUC of single detection of CTSB and NOX4(Z=4.066,P<0.001,Z=3.801,P<0.001).Conclusion The serum levels of CTSB and NOX4 in S-AKI patients are elevated,and can indirectly reflect kidney function.CTSB combined with NOX4 can significantly improve the prediction efficiency of poor prognosis in S-AKI patients,which has potential ap-plication value for clinical treatment and nursing.
10.Bone density and bone metabolism in plasmapheresis donors
Wan LI ; Changqing LI ; Yongjun CHEN ; Xi YANG ; Zhiwei LI ; Ya WANG
Chinese Journal of Blood Transfusion 2024;37(1):51-57
【Objective】 To investigate the level of serum bone metabolism and biochemical markers and bone density of plasmapheresis donors, and to provide scientific basis for ensuring the health and safety of plasmapheresis donors in China. 【Methods】 A total of 437 plasmapheresis donors from Linwu plasmapheresis station in Hunan Province from July 1 to September 30, 2022 were recruited to determine the levels of total serum calcium, albumin, serum 25-hydroxyvitamin D (25OHD), serum type I procollagen N-terminal propeptide (P1NP), and collagen type 1 crosslinked carboxyl-terminal peptide (β-CTX). Dual-energy X-ray method was used to measure the bone density of the anteroposterior lumbar spine (L1-L4) and bilateral femoral neck bone density of plasmapheresis donors. Plasmapheresis donors were grouped according to the type of plasma donation (first-time and repeat plasmapheresis donors) and the total number of plasma donations to assess the differences in bone density and serum bone metabolism biochemical markers between groups. The dose-response relationship between the total number of plasmapheresis donations and biochemical indexes was analyzed by limiting cubic spline, and the influencing factors of different indexes were explored by multiple linear regression. 【Results】 A total of 437 plasmapheresis donors were included in this study, including 187 first-time plasmapheresis donors and 250 repeat plasmapheresis donors. There were no significant differences in bone density and prevalence of osteoporosis between first-time donors and repeat donors (P>0.05). There was also no significant difference in bone density levels between groups of total number of plasmapheresis donations. The levels of albumin and 25OHD decreased with the increase of the total number of plasma donations, while the serum P1NP level was positively correlated with the total number of plasma donations. The results of the restriction cubic spline showed that the total number of plasmapheresis donations had a nonlinear dose-response relationship with 25OH and P1NP (P<0.05). The results of multiple linear regression showed that the frequency of plasmapheresis donation was the influencing factor of 25OHD, and the total number of plasmapheresis donation was the influencing factor of P1NP. 【Conclusion】 Plasmapheresis donation does not affect the bone health of donors and increase the risk of osteoporosis due to the use of long-term anticoagulants, but it will increase the osteogenic activity of plasmapheresis donors. It is recommended that middle-aged and elderly plasmapheresis donors supplement vitamin D appropriately.

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