1.Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease
Tianzhong PAN ; Peng DING ; Aijie HUANG ; Baolin TANG ; Kaidi SONG ; Guangyu SUN ; Yue WU ; Shiying YANG ; Xingchi CHEN ; Dongyao WANG ; Xiaoyu ZHU
Chinese Medical Journal 2024;137(10):1207-1217
Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.
2.Effect of light pattern on dopamine transporter in the guinea pig retina
Jingjing WANG ; Kai LI ; Kaidi XIANG ; Jun CHEN ; Linlin DU ; Jinliuxing YANG ; Sichen LIU ; Ling WANG ; Xiangui HE
Chinese Journal of Experimental Ophthalmology 2024;42(4):309-314
Objective:To study the distribution and changes of dopamine transporter (DAT) in guinea pig eyes under different light patterns.Methods:Thirty-six 3-week-old white ordinary-grade guinea pigs were randomly selected and divided into groups of 10 000 lx, 5 000 lx, and 500 lx, with 12 guinea pigs in each group exposed to strong light, medium strong light, and normal light, respectively.Each group was randomly divided into 3 subgroups, with 4 guinea pigs in each subgroup.The 3 subgroups of 500 lx group received light exposure for 5, 20, and 40 minutes, respectively.The 3 subgroups of 5 000 lx group received light exposure for 2, 4, and 40 minutes, respectively.The 3 subgroups of 10 000 lx group received light exposure for 2, 5, and 20 minutes, respectively.After light treatment, each group of guinea pigs was injected with 99mTc-TRODAT-1 for SPECT DAT imaging, and image data were collected by Micro-SPECT.The region of interest (ROI) of guinea pig retinas was analyzed using Micro-CT software.The counts of ROI were expressed as Sum, which reflected the relative distribution or density of DAT.The DAT density between experimental and control eyes of guinea pigs after light exposure, the differences in DAT density between guinea pig eyes under different light intensities, the differences in DAT density between guinea pig eyes after different light durations, and the cumulative and interactive effects of light intensity and light duration on DAT aggregation in guinea pigs were compared.Another 3 guinea pigs were selected, and after light exposure, the 3 guinea pigs' eyes underwent continuous image acquisition for 6 hours at 20-minute intervals, and 18 images per guinea pig were acquired to analyze the trend of DAT density in guinea pig eyes over time.This study was approved by the Ethics Committee of Shanghai General Hospital (No.2020SQ196). Results:The DAT density (Sum value) of experimental eyes at 500, 5 000, and 10 000 lx were 5 598.97±3 159.38, 8 636.78±2 503.16, and 7 407.39±2 053.41, respectively, significantly higher than 4 388.89±2 902.90, 5 981.92±3 057.44, and 5 091.32±2 039.36 of control eyes ( t=5.31, 4.69, 11.80; all at P<0.001). At 500 lx, there was a statistically significant difference in DAT density between the experimental and control eyes of guinea pigs at different light exposure durations ( F=14.01, P<0.01), while no significant difference was found at other light intensities at different light exposure durations (both at P>0.05). When the light exposure time was 5 minutes, the difference in DAT density between the experimental and control eyes of guinea pigs was significantly greater in the 10 000 lx group than in the 500 lx group ( t=-13.22, P<0.001). There was no statistically significant difference between different groups at other light exposure durations (all at P>0.05). No cumulative or interactive effects of light intensity and light duration were found on the differences in DAT density (all at P>0.05). Continuous scanning after illumination showed that DAT density in guinea pig retinas first increased to a peak over time and then gradually returned to normal values. Conclusions:Light, even under moderate or normal light levels, can cause an increase in the secretion of DAT in the retina and stimulate the production of DAT.Light intensity and duration have no cumulative or interactive effects on the distribution and density of retinal DAT.
3.Targeting ferroptosis and ferritinophagy:new targets for cardiovascular diseases
LUAN YI ; YANG YANG ; LUAN YING ; LIU HUI ; XING HAN ; PEI JINYAN ; LIU HENGDAO ; QIN BO ; REN KAIDI
Journal of Zhejiang University. Science. B 2024;25(1):1-22
Cardiovascular diseases(CVDs)are a leading factor driving mortality worldwide.Iron,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for decades.Iron-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and CVDs.Furthermore,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to CVDs.This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in CVDs.Furthermore,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs.Collectively,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.
4.Effect of endovascular treatment on thrombosis of autogenous arteriovenous fistula
Wen LI ; Fanli WANG ; Yanli YANG ; Fengqin REN ; Fulei MENG ; Kaidi ZHANG ; Haiyan ZHAO ; Lihong ZHANG ; Lin RUAN
Chinese Journal of Nephrology 2024;40(2):118-123
Objective:To investigate the effectiveness and safety of ultrasound-guided endovascular therapy for autogenous arteriovenous fistula (AVF) thrombosis.Methods:It was a single-center retrospective cohort study. Data of patients undergoing ultrasound-guided intravascular therapy due to AVF thrombosis in the First Hospital of Hebei Medical University from August 2018 to June 2021 were analyzed. According to different surgical procedures, the patients were divided into two groups. Patients treated with percutaneous transluminal angioplasty (PTA) + drilling thrombectomy were in group A, and patients treated with PTA only were in group B. After 1 year of follow-up, the surgical technique success rate, primary patency rate, secondary patency rate and complications were compared between the two groups.Results:A total of 152 patients were enrolled, including 74 in group A and 78 in group B. There were no significant differences in gender, age, proportion of patients with diabetes and hypertension, and thrombosis time of AVF between the two groups (all P>0.05). Compared with group B, the diameter and length of thrombus in group A were larger [13.0(9.0, 16.0) mm vs. 6.0(5.0, 6.5) mm, Z=-9.362, P<0.001; 12(8, 15) cm vs. 3(3, 4) cm, Z=-10.061, P<0.001], and the establishment time of AVF was longer [5(2, 7) years vs. 2(1, 5) years, Z=-2.698, P=0.007]. Among the overall patients, the success rate of surgery was 96.7% (147/152), and the success rate of surgery was 95.9% (71/74) in group A and 97.4% (76/78) in group B respectively, with no statistical difference ( χ2=0.004, P=0.952). Kaplan-Meier survival analysis showed that, overall, the primary patency rate at 3rd, 6th and 12th month after operation was 87.1%, 71.4% and 56.6%, and the secondary patency rate was 97.1%, 96.4% and 94.1%, respectively. The primary patency rate of group A at 3rd, 6th and 12th month was 82.4%, 66.7% and 53.6%, and the secondary patency rate was 95.7%, 94.2% and 89.7%, respectively. The primary patency rate of group B at 3rd, 6th and 12th month was 91.5%, 73.2% and 59.7%, and the secondary patency rate was 98.6%, 98.6% and 98.5%, respectively. There was no significant difference in the primary and secondary patency rate between group A and group B at 3rd, 6th and 12th month (all P>0.05). The duration of operation in group A was longer than that in group B [2.0(1.9, 2.0) h vs. 2.0(1.0, 2.0) h, Z=-5.181, P<0.001], but no serious complications occurred in both groups. Conclusion:The two surgical methods are effective, safe and reliable in the treatment of AVF thrombosis, and have high clinical application value.
5.Research progress on comorbidity management for aged cardiovascular disease patients
Dongmei WU ; Bing LIU ; Longti LI ; Yongjian LIU ; Yingmei HE ; Kaidi YANG ; Jinghua TENG
Chinese Journal of Modern Nursing 2023;29(32):4341-4345
This article provides a comprehensive overview of the concepts and types of comorbidities associated with cardiovascular diseases in the aged, summarizing their impacts on patients and potential intervention measures. The aim is to offer a reference for future research related to comorbidity management in aged cardiovascular disease patients in China.
6.The value of growth differentiation factor 15 in early diagnosis of acute chest pain
Shangqing CHANG ; Yunjing SHENG ; Qinrui XING ; Kaidi YANG ; Tingli WANG ; Xiangqian GUO ; Haiyan ZHU
Chinese Journal of Emergency Medicine 2021;30(6):694-698
Objective:To explore the value of growth differentiation factor 15 (GDF15) in the early diagnosis of acute chest pain.Methods:A total of 96 patients with acute chest pain admitted to the Emergency Department of Hainan Hospital of PLA General Hospital from January to November 2020 were retrospectively collected. The sex, age, troponin T, creatine kinase, creatine kinase isoenzyme, GDF15 and B-type natriuretic peptide of patients within 30 min after admission were recorded, and the differences of each index in different groups were compared. ROC curve was drawn to evaluate the diagnostic value of GDF15 and TNT/BNP in acute coronary syndrome (ACS). The Gensini score, left ventricular ejection fraction, length of stay in hospital and the number of stents were calculated, and the correlation between these indexes and GDF15 concentration was evaluated.Results:The general trend of acute chest pain was more male than female (72.92% vs. 27.08%) , the oldest group was the UA group (64.67 ± 13.87) years old , the youngest group was cardiac arrest group (47.29 ± 9.99) years old . There were higher rates of hypertension in the STEMI group, NSTEMI group and UA group, and none of the groups showed significant advantage in diabetes. The GDF15 concentration was higher in ACS related chest pain group [(2.360 ± 1.710) ng/mL vs. (1.380 ± 1.040) ng/mL, P<0.01]. The area under the Receiver Operating Characteristic Curve (AUC) of GDF15 combined with TNT was up to 0.863. GDF15 concentration was negatively correlated with ejection fraction, positively correlated with Gensini score, positively correlated with the number of stents implanted, and positively correlated with the length of hospital stay. Conclusions:GDF15 is valuable in the diagnosis and prognosis of acute chest pain. The combination of GDF15 and TNT can improve the diagnostic rate of ACS.
7.Pharmacodynamic study of magnesium isoglycyrrhizinate in HBV transgenic mouse model
Hongjiang XU ; Wei SHI ; Wei SONG ; Ying ZHANG ; Kaidi ZHAO ; Yinsheng ZHANG ; Ling YANG ; Jinan WANG
Journal of China Pharmaceutical University 2019;50(4):475-480
This study aims to discuss the therapeutic effect of magnesium isoglycyrrhizinate on hepatitis B virus(HBV)transgenic mouse and its effect on cellular immunity and liver inflammation. The changes of serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)activity, the difference of serum hepatitis B surface antigen(HBsAg), liver tissue HBsAg mRNA, and the pathological morphological changes of liver tissue were detected to investigate the hepatic inflammatory lesions and the efficacy of magnesium isoglycyrrhizinate in HBV transgenic mouse. Peripheral blood lymphocytes were classified by flow cytometry, and serum cytokines were detected by cytometric bead array(CBA)to explore the mechanism of magnesium isoglycyrrhizinate to reduce hepatic inflammatory lesions in HBV transgenic mouse. After grouping HBV transgenic mouse with serum transaminase activity and 35 days of continuous administration, serum transaminases level in magnesium isoglycyrrhizinate [15 mg/(kg ·d)] group was significantly lower than that in control group(P< 0. 05), serum HBsAg protein and liver tissue HBsAg mRNA increased with time, but there was no significant difference between the two groups. The main pathological changes of liver were liver cell swelling, necrosis and focal inflammatory cell infiltration, and the pathological changes of liver in magnesium isoglycyrrhizinate group were lighter than those in control group. The number of CD8+ cells in the blood of magnesium isoglycyrrhizinate group was significantly less than that in the control group(P< 0. 05)and the CD4+/CD8+ cell ratio was significantly higher than that in the control group(P< 0. 05). The content of inflammatory cytokines in serum of magnesium isoglycyrrhizinate group decreased significantly(P< 0. 05). Magnesium isoglycyrrhizinate can regulate the immune function of HBV transgenic mouse, decrease the infiltration of inflammatory cells in hepatic tissue and hepatocyte injury, but do not affect the expression of hepatocyte HBsAg.
8.Value of polypeptide-based nanomagnetic circulating tumor cells detection for the differential diagnosis of pulmonary nodules
LI Kaidi ; LIANG Naixin ; LIU Hongsheng ; LI Li ; HUANG Cheng ; QIN Yingzhi ; HAN Zhijun ; BING Zhongxing ; LIU Lei ; XU Yuan ; XU Huihui ; YANG Yanlian ; PENG Jiaxi ; HUO Li ; LI Fang ; HU Zhiyuan ; LI Shanqing
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(7):560-566
Objective To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results CTC count of the malignant group was significantly higher than that of the benign group (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/ml vs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.
9.Progress in researches on exosomes in non-small cell lung cancer
Kaidi LI ; Wenzhe LI ; Ling ZHU ; Yanlian YANG ; Naixin LIANG ; Shanqing LI
Basic & Clinical Medicine 2017;37(4):561-566
Exosomes are vesicle-like structures generated and secreted actively by all kinds of cells.They contain proteins, nucleic acids and also lipids from the original cells, functioning in interactions between cells by shuttling cellular cargoes, and regulation of immune response in the microenvironment.Besides, they play important roles in the oncogenesis and progression of lung neoplasms.Considerable studies have demonstrated great potentials of exosomal proteins and microRNAs as biomarkers for diagnosis, prognosis prediction and treatment of lung cancers, including immunotherapy and targeted delivering of anti-tumor drugs based on exosomes.
10.Evaluation of clinical efficacy of single-unit unrelated umbilical cord blood transplantation based on umbilical cord blood provided by China's public cord blood bank
Jianjun LI ; Huilan LIU ; Xiaoyu ZHU ; Baolin TAO ; Kaidi SONG ; Changcheng ZHENG ; Liangquan GENG ; Juan TONG ; Lei ZHANG ; Xuhan ZHANG ; Wei WEI ; Wei LU ; Feng ZHOU ; Jieying WU ; Qiang CHEN ; Yasheng YU ; Zhongfa JIANG ; Junye YANG ; Zimin SUN
Chinese Journal of Organ Transplantation 2017;38(2):84-89
Objective To study the curative efficacy and safety of single-unit umbilical cord blood transplantation (sUCBT) for malignant hematologic diseases,which is provided by China's public cord blood bank.Methods We retrospectively analyzed 409 cases of malignant hematologic diseases who accepted myeloablative single-unit unrelated donor UCBT without ATG at our center between May 2008 and December 2016.A comparative analysis was made on the total nuclear cells (TNC) of the umbilical cord blood before freezing and after thawing,the cells of CD34+,the recovery rate of cells and the clinical effect of UCBT.Result 409 units of umbilical cord blood used in UCBT respectively came from eight China's public cord blood banks.The average TNC of 409 units of umbilical cord blood before freezing and after the tubular recovery were respectively 18.5 × 108 and 16.34 × 108 (p =0.000).The average recovery rate of the tubular recovery was 88.5%,and there was significant difference among cord blood banks (P =0.000).The average TNC of umbilical cord blood before freezing and transfusion were respectively 18.5 × 108 and 15.86 × 108 (p =0.000).The average recovery rate of umbilical cord blood transfusion was 85.9%,with the difference being significant among cord blood banks (P =0.000).The average number of CD34+ cells before freezing and after the tubular recovery was 11.18 × 106and 8.68 × 106 (p =0.000).The average recovery rate of CD34+ cells after the tubular recovery was 80.75 %,with the difference being significant among the cord blood banks (P =0.000).At 42nd day after UCBT,the cumulative incidence of neutrophil engraftment was 95.4%,and the median time of the engraftment was 17 days (11-38 days).The cumulative incidence of platelet engraftment at 120th day was 84.6%,and the median time of the engraftment was 36 days (14-93 days).The cumulative incidence of erythrocyte engraftment at 60th day was 92%,and the median time of engraftment was 22 days (9d-60 days).After the umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of engraftment.The P values for cumulative incidence of neutrophil,platelet and erythrocyte engraftment were respectively 0.004,0.01 and 0.000 2,with the differences being statistically significant.At 100th day after UCBT,the cumulative incidence of Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees of acute graft-versus-host disease (aGVHD) was respectively 28.63% and 15.7%.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of aGVHD.There was no significant difference between Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees (P =0.809 and 0.68 respectively).At 3rd year after UCBT,the cumulative incidence of relapse was 15.89%.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the cumulative incidence of relapse (P =0.898).At 3rd year after UCBT,the overall survival (OS) rate and disease free survival (DFS) rate were respectively 66.7% and 59%.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in OS and DFS.There was no significant difference in OS and DFS (P =0.566 and 0.703 respectively).At 3rd year after sUCBT,the rate of graft-versus-host diseases/relapse-free survival (GRFS) was 54.3%.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the rate of GRFS (P =0.449).Conclusion The umbilical cord blood provided by China's public cord blood bank was used in UCBT.It has a high safety and good efficacy in treating malignant hematologic diseases.But it needs to set up the standardized and normalized quality-control system of umbilical cord blood for China's public cord blood bank.

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