1.Estimation of genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using benchmark dose
Junli LIU ; Yu DING ; Xueqing CHENG ; Zhengli YANG ; Kelei QIAN ; Jing XU ; Yiyun FAN ; Dongsheng YU ; Zhiqing ZHENG ; Jun YANG ; Ning WANG ; Xinyu HONG
Journal of Environmental and Occupational Medicine 2024;41(4):425-430
Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg−1 ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg−1; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg−1) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg−1 and 21.90 mg·kg−1, and those of male mice were calculated to be 58.62 mg·kg−1 and 54.31 mg·kg−1, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg−1 and 11.99 mg·kg−1 for female mice, and 16.28 mg·kg−1 and 10.47 mg·kg−1 for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg−1 and 19.92 mg·kg−1 for female mice, and 24.74 mg·kg−1 and 14.08 mg·kg−1 for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg−1, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.
2.Preparation and in vivo Distribution of Essential Oil from Alpinia zerumbet Fructus Encapsulated Nanoemulsions
Jinzhuan XU ; Lili ZHANG ; Zhengli ZHOU ; Shan XU ; Xiang ZHOU ; Lei HUANG ; Zipeng GONG ; Yi CHEN ; Xiangchun SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):126-133
ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus(EOFAZ) and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin(VBCP-BSA) was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier, vitamin B12(VB12) as absorption enhancer, and medium chain triglycerides mixed with EOFAZ as oil phase, the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size, particle size distribution, surface Zeta potential, EOFAZ content and appearance and morphology of the nanoemulsions were characterized, and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier, the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB12. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge, and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%, which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ, promote oral absorption and enhance liver distribution, which can provide experimental basis for the development of oral EOFAZ liver protection preparations.
3.Effects of inhalation of polyhexamethylene guanidine disinfectant aerosol on immune organs and immune cells in mice
Zhengli YANG ; Naimin SHAO ; Yu DING ; Jing XU ; Junli LIU ; Xi LIU ; Kelei QIAN ; Xinyu HONG
Journal of Environmental and Occupational Medicine 2024;41(8):855-860
Background The respiratory toxicity of inhaled polyhexamethylene guanidine (PHMG) has been extensively studied since the humidifier disinfectant incident. However, the impacts of inhalation of PHMG on the immune system are not comprehensively studied yet. Objective To explore the effects of inhalation of PHMG disinfectant aerosol on major immune organs and immune cells in mice. Methods Thirty male C57BL/6J mice (6-8 weeks old) were randomly divided into three groups: control, low-dose (0.1 mg·m−3 PHMG), and high-dose (1.0 mg·m−3 PHMG), with ten mice in each group. The mice were administered by oral-nasal inhalation of PHMG aerosol for 4 h per day, 5 d per week for 4 weeks consecutively. After designed treatment, venous blood was collected from the inner canthus of the eyes of mice and peripheral hematological indicators were measured with a blood analyzer. Then the mice were sacrificed by cervical dislocation and the lung, thymus, spleen, and femur were isolated. Lung, thymus, and spleen were weighed and organ coefficients were calculated, and single cell suspensions of thymus, spleen, and bone marrow were prepared to analyze lymphocytes phenotypes and proportions by flow cytometry. Results The body weight of mice in the high-dose group was lower than that of mice in the control group (P<0.01) from the 7th day of inhalation, and decreased by 15.74% compared with that of mice in the control group at the end of inhalation (P<0.01). The lung coefficients of both the low-dose and high-dose groups were higher than that of the control group (P<0.01), the thymus coefficient of mice in the high-dose group was lower than that of the control group (P<0.05), but the spleen coefficient did not change significantly (P>0.05). Leukocyte count [(1.49±0.22)×109·L−1], lymphocyte count [(0.96±0.36)×109·L−1] and its proportion [(63.13±14.96)%] in the peripheral blood of mice in the high-dose group were lower than those in the control group [(2.69±0.25)×109·L−1, (2.33±0.28)×109·L−1, and (86.23±3.40)%, respectively] (P<0.01), whereas red blood cell count [(12.32±0.46)×1012·L−1], hemoglobin count [(175.25±4.65) g·L−1], and hematocrit [(53.55±0.70)%] in the peripheral blood of mice in the high-dose group were higher than those in the control group [(11.11±0.37)×1012·L−1, (160.67±4.04) g·L−1, and (45.10±9.75)%, respectively] (P<0.05). Compared with the control group, the proportion of CD4+ CD8+ double-positive T cells decreased (P<0.05), the proportions of CD4+ T cells and CD8+ T cells increased (P<0.05), and the amounts of CD8+, CD4+ CD8+, CD4+, and CD4- CD8- cells decreased (P<0.05) in the thymus of mice of the high-dose group, the proportion of CD4+ T cells in the spleen of the high-dose group increased (P<0.05), the proportions and amounts of T cells, CD4+ T cells, and CD8+ T cells in the bone marrow of the high-dose group increased (P<0.05). Conclusion Inhalation of PHMG may cause thymic atrophy, disrupt T-lymphocyte development, and lead to an imbalance in the number of immune cells in the bone marrow, peripheral blood, and spleen, suggesting that inhalation of PHMG induces immune dysfunction.
4.Severe cardiotoxic characteristics associated with allogeneic hematopoietic stem cell transplantation preconditioning in patients with aplastic anemia
Xue MING ; Yuanyuan ZHANG ; Tingting HAN ; Jingzhi WANG ; Xiaodong MO ; Fengrong WANG ; Chenhua YAN ; Yu WANG ; Yuhong CHEN ; Zhengli XU ; Feifei TANG ; Ting ZHAO ; Kaiyan LIU ; Xiaohui ZHANG ; Xiaojun HUANG ; Lanping XU
Chinese Journal of Internal Medicine 2024;63(11):1096-1103
Objective:To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA).Methods:This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People′s Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method.Results:In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n=26). Most patients ( n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions:Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.
5.The establishment of quality indicator system of interventional nursing based on Donabedian quality structure model
Zhengli HUANG ; Xiaoyan WANG ; Youhua XUE ; Xuemei WANG ; Yang XU
Journal of Interventional Radiology 2024;33(7):785-789
Objective To establish a quality indicator system of interventional nursing.Methods Taking Donabedian quality structure model as the theoretical basis and through literature analysis,expert meeting and summarizing the clinical problems,the first draft about interventional nursing care quality indicators was composed,which included 3 first-level indicators,12 second-level indicators and 55 third-level indicators.A total of 27 experts on interventional nursing and nursing administration were selected from 25 grade-3A level hospitals in 13 provinces and cities of China.The Delphi method was used to conduct two rounds of expert correspondence consultation,and the quality indicator system of interventional nursing was established.Results Finally,a quality indicator system of interventional nursing,which included 3 first-level indicators,7 second-level indicators and 29 third-level indicators,was formulated.In both the two rounds of expert letter inquiry,the positive coefficient and authority coefficient were 100%and 0.95 respectively.The coefficient of variation of each index in the first and the second round of expert letter inquiry was 0-0.25 and 0-0.21 respectively.In the first round of expert letter inquiry,the Kendall harmony coefficients of the first-level,second-level and third-level indexes were 0.672,0.271 and 0.341 respectively,while in the second round of expert letter inquiry,the Kendall harmony coefficients of the first-level,second-level and third-level indexes were 0.462,0.475 and 0.330 respectively,the differences were statistically significant(all P<0.01).Conclusion The quality indicator system of interventional nursing established in this study carries a relatively high reliability and scientific nature,and it can provide reference for evaluating and monitoring the safety and quality control in interventional nursing.
6.The impact of donor human leukocyte antigen-Bw4 allele on natural killer cell reconstitution and transplant-related mortality in haploidentical transplantation
Ming ZHAO ; Zhengli XU ; Xingxing YU ; Yiyang DING ; Yingjun CHANG ; Xiaohui ZHANG ; Kaiyan LIU ; Xiaojun HUANG ; Xiangyu ZHAO
Chinese Journal of Hematology 2024;45(5):453-461
Objective:To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion.Methods:This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning.Results:Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion:In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.
7.To construct Chinese hematology community
Chinese Journal of Hematology 2024;45(6):521-524
The development of hematology in China has gradually begun since the 1950s. After several generations of hard work, it has grown into a young but vibrant discipline. The development of Chinese hematology has experienced rapid rise and steady growth, but there is still a gap with the international level of hematology development. Only by constructing a Chinese community of hematology and forming a joint force to promote the development of hematology can we better realize the Chinese Dream in the field of hematology.
8.Rituximab based treatment in pediatric Epsstain Bar Virus associated lymphocyte proliferative diseases after aplastic anemia with haplo-identical transplantation:a prospective single centre study
Feng ZHANG ; Guanhua HU ; Pan SUO ; Zhengli XU ; Lu BAI ; Huifang WANG ; Shanyamei HUANG ; Lanping XU ; Yingjun CHANG ; Xiaohui ZHANG ; Xiaojun HUANG ; Yifei CHENG
Chinese Journal of Hematology 2024;45(7):678-682
Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.
9.Prognostic analysis of 8 patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation
Yun HE ; Zhengli XU ; Rui MA ; Jing LIU ; Yuanyuan ZHANG ; Meng LYU ; Xiaodong MO ; Chenhua YAN ; Yuqian SUN ; Xinyu ZHANG ; Yu WANG ; Xiaohui ZHANG ; Xiaojun HUANG ; Lanping XU
Chinese Journal of Hematology 2024;45(9):816-820
Objective:To evaluate the safety of patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A retrospective analysis of the clinical characteristics and prognosis of eight patients with hepatic adenoma who underwent allo-HSCT in the Hematology Department of Peking University People’s Hospital from January 2010 to March 2024 was conducted.Results:Of the eight patients who underwent allo-HSCT with hepatic adenoma, one patient was considered MDS-h transfusion-dependent and seven had aplastic anemia. The median age of the patients was 23 years (13-48 years). The median time from the diagnosis of AA or MDS to transplantation was 14 years (6-24 years), whereas the median time from taking androgens to diagnosing hepatic adenoma was 9 years (5-13 years). Six cases underwent haplo-HSCT, one case underwent matched unrelated donor HSCT, and one case underwent matched related donor HSCT. All patients achieved neutrophil engraftment at a median time of 11.5 days (11-20 days) and PLT engraftment within 60 days at a median of 19 days (10-37 days) after haplo-HSCT. Moreover, seven patients developed CMV anemia after transplantation, three patients had hemorrhagic cystitis, and two patients developed acute GVHD. During and after transplantation, eight patients did not show severe liver function damage or rupture of hepatic adenoma. In relation to imaging size, four patients showed varying degrees of reduction in hepatic adenoma size after transplantation, whereas four patients did not show significant changes in hepatic adenoma size after transplantation. The median follow-up time was 540.5 (30-2 989) days. Of the eight patients, six survived and two died. Furthermore, no direct correlation was observed between death and hepatic adenoma.Conclusion:Patients with hepatic adenomas undergoing allo-HSCT are not contraindications for transplantation, which will not increase transplant-related mortality.
10.Bridging chimeric antigen receptor T-cell before transplantation improves prognosis of relapsed/refractory B-cell acute lymphoblastic leukemia.
Xiangyu ZHAO ; Haotian WU ; Yifei CHENG ; Zhengli XU ; Yuhong CHEN ; Yingjun CHANG ; Yu WANG ; Xiaohui ZHANG ; Lanping XU ; Xiaojun HUANG
Chinese Medical Journal 2023;136(16):2011-2013

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