1.Research Progress on Mechanism of Tumor-Associated Immune Thrombocytopenia
Guimin LIU ; Huimin ZHU ; Zhiyong CHENG ; Wei QIN
Cancer Research on Prevention and Treatment 2025;52(10):869-874
Thrombocytopenia is a common complication during the treatment of malignant tumors. It can lead to insufficient doses of chemotherapy drugs or delayed chemotherapy, shorten patients’ survival time, and affect prognosis. Thrombocytopenia has two types: cancer treatment-induced thrombocytopenia and tumor-associated immune thrombocytopenia. The latter is relatively rare, and its pathogenesis may be related to immune dysregulation. Current studies have shown that gene polymorphism and methylation are involved in tumor-associated immune thrombocytopenia. The pathogenesis and treatment of tumor-associated immune thrombocytopenia are discussed in this article.
2.Neuroprotective effect of hypericin on mice after acute cerebral infarction by ameliorating neuron ferroptosis and cuproptosis
Guimin JIN ; Tingting DUAN ; Yuanyuan ZHU ; Ming YU ; Yuhao XU
Chinese Journal of Neuromedicine 2025;24(2):109-118
Objective:To investigate the effect of hypericin (Hyp) on neurologic impairment, ferroptosis and cuproptosis in mice with acute cerebral infarction.Methods:Sixty 8-week old male C57BL/6 mice were randomly divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, MCAO+Hyp low-dose treatment group (L-Hyp group), and MCAO+Hyp high-dose treatment group (H-Hyp group), with 15 mice in each group. Intraluminal filament MCAO models in the later 3 groups were established. Saline was given intraperitoneally into the sham-operated group and MCAO group, and Hyp was given intraperitoneally at 0.5 mg/kg or 1 mg/kg into the L-Hyp group and H-Hyp group 24 hours after modeling. Twenty-four hours after Hyp, neurologic function was assessed using Garcia score, grip strength test, and fatigue baton test; brain tissue edema was assessed by dry-wet weight method; neuronal necrosis, survival and apoptosis were detected by HE staining, Nissl staining and TUNEL, respectively; ferroptosis and oxidative stress were assessed using iron assay kit, and reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) assay kits; cuproptosis was assessed using copper assay kit and mitochondrial oxidative phosphorylation was evaluated by mitochondrial respiratory chain complex Ⅲ and Ⅳ activity detection kits; morphological changes in neuronal mitochondria after ferroptosis and cuproptosis were observed by electron microscopy; protein expressions of ferroptosis-associated solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), cuproptosis-associated solute carrier family 31 member 1 (SLC31A1), and ferredoxin 1 (FDX1) were detected by Western blotting.Results:(1) Compared with the MCAO group, the L-Hyp group and H-Hyp group had decreased modified Garcia score and brain water content, increased grip strength and rod-turning time, decreased number of necrotic and apoptotic neurons, increased number of survived neurons, decreased Fe 2+, ROS and MDA levels, increased GSH level and mitochondrial respiratory control rate, and decreased copper content, with significant differences ( P<0.05); and the above changes in the H-Hyp group were more obvious than those in the L-Hyp group, with significant differences ( P<0.05). Compared with the MCAO group, neurons in the L-Hyp group and H-Hyp group had significantly improved status in mitochondrial shrinkage, vacuolation, reduced cristulation, increased membrane density, ruptured cell membrane, endoplasmic reticulum damage and chromatin disruption ( P<0.05); and the H-Hyp group had signficantly more obvious improvement than the L-Hyp group ( P<0.05). (2) Compared with the MCAO group (0.38±0.09, 0.28±0.05), the L-Hyp group and H-Hyp group had significantly increased protein expressions of SLC7A11 and GPX4 (0.83±0.11, 0.49±0.06; 1.27±0.08, 0.84±0.04; P<0.05); the H-Hyp group had significantly higher SLC7A11 and GPX4 expressions than the L-Hyp group ( P<0.05). Compared with the MCAO group (2.76±0.17, 0.67±0.07), the L-Hyp group and H-Hyp group had significantly decreased protein expressions of SLC31A1 and FDX1 (1.72±0.07, 0.51±0.05; 1.12±0.06, 0.34±0.05; P<0.05); the H-Hyp group had significantly lower SLC31A1 and FDX1 expressions than the L-Hyp group ( P<0.05). Conclusion:Hyp can ameliorate ferroptosis and cuproptosis by regulating the protein expressions of SLC7A11, GPX4, SLC31A1 and FDX1, to alleviate oxidative stress injury in MCAO mice, thereby promoting the recovery of neurological function.
3.Neuroprotective effect of hypericin on mice after acute cerebral infarction by ameliorating neuron ferroptosis and cuproptosis
Guimin JIN ; Tingting DUAN ; Yuanyuan ZHU ; Ming YU ; Yuhao XU
Chinese Journal of Neuromedicine 2025;24(2):109-118
Objective:To investigate the effect of hypericin (Hyp) on neurologic impairment, ferroptosis and cuproptosis in mice with acute cerebral infarction.Methods:Sixty 8-week old male C57BL/6 mice were randomly divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, MCAO+Hyp low-dose treatment group (L-Hyp group), and MCAO+Hyp high-dose treatment group (H-Hyp group), with 15 mice in each group. Intraluminal filament MCAO models in the later 3 groups were established. Saline was given intraperitoneally into the sham-operated group and MCAO group, and Hyp was given intraperitoneally at 0.5 mg/kg or 1 mg/kg into the L-Hyp group and H-Hyp group 24 hours after modeling. Twenty-four hours after Hyp, neurologic function was assessed using Garcia score, grip strength test, and fatigue baton test; brain tissue edema was assessed by dry-wet weight method; neuronal necrosis, survival and apoptosis were detected by HE staining, Nissl staining and TUNEL, respectively; ferroptosis and oxidative stress were assessed using iron assay kit, and reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione (GSH) assay kits; cuproptosis was assessed using copper assay kit and mitochondrial oxidative phosphorylation was evaluated by mitochondrial respiratory chain complex Ⅲ and Ⅳ activity detection kits; morphological changes in neuronal mitochondria after ferroptosis and cuproptosis were observed by electron microscopy; protein expressions of ferroptosis-associated solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), cuproptosis-associated solute carrier family 31 member 1 (SLC31A1), and ferredoxin 1 (FDX1) were detected by Western blotting.Results:(1) Compared with the MCAO group, the L-Hyp group and H-Hyp group had decreased modified Garcia score and brain water content, increased grip strength and rod-turning time, decreased number of necrotic and apoptotic neurons, increased number of survived neurons, decreased Fe 2+, ROS and MDA levels, increased GSH level and mitochondrial respiratory control rate, and decreased copper content, with significant differences ( P<0.05); and the above changes in the H-Hyp group were more obvious than those in the L-Hyp group, with significant differences ( P<0.05). Compared with the MCAO group, neurons in the L-Hyp group and H-Hyp group had significantly improved status in mitochondrial shrinkage, vacuolation, reduced cristulation, increased membrane density, ruptured cell membrane, endoplasmic reticulum damage and chromatin disruption ( P<0.05); and the H-Hyp group had signficantly more obvious improvement than the L-Hyp group ( P<0.05). (2) Compared with the MCAO group (0.38±0.09, 0.28±0.05), the L-Hyp group and H-Hyp group had significantly increased protein expressions of SLC7A11 and GPX4 (0.83±0.11, 0.49±0.06; 1.27±0.08, 0.84±0.04; P<0.05); the H-Hyp group had significantly higher SLC7A11 and GPX4 expressions than the L-Hyp group ( P<0.05). Compared with the MCAO group (2.76±0.17, 0.67±0.07), the L-Hyp group and H-Hyp group had significantly decreased protein expressions of SLC31A1 and FDX1 (1.72±0.07, 0.51±0.05; 1.12±0.06, 0.34±0.05; P<0.05); the H-Hyp group had significantly lower SLC31A1 and FDX1 expressions than the L-Hyp group ( P<0.05). Conclusion:Hyp can ameliorate ferroptosis and cuproptosis by regulating the protein expressions of SLC7A11, GPX4, SLC31A1 and FDX1, to alleviate oxidative stress injury in MCAO mice, thereby promoting the recovery of neurological function.
4.Clinical diagnostic value of combined detection of serum and bronchoalveolar lavage fluid galactomannan for invasive pulmonary aspergillosis in non-neutropenic children
Zhengli LI ; Chunmei ZHU ; Guimin HUANG ; Li CHANG
Chinese Journal of Microbiology and Immunology 2022;42(5):409-414
Objective:To investigate the clinical diagnostic value of combined detection of serum and bronchoalveolar lavage fluid (BALF) galactomannan (GM) for invasive pulmonary aspergillosis (IPA) in children with non-neutropenia.Methods:An analysis was made on 100 children with non-neutropenia suspected of invasive pulmonary aspergillosis in the respiratory ward of the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2019 to March 2020. All of them were tested by serum and BALF GM tests as well as sputum and BALF culture for fungi. The sensitivity, specificity and accuracy of serum and BALF GM in the diagnosis of IPA in non-neutropenic children were analyzed. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the clinical diagnostic value of serum and BALF GM tests for IPA in children with non-neutropenia.Results:The recruited 100 cases included one confirmed case, 85 clinically diagnosed cases and two suspected cases, while the 12 cases were excluded. The accuracy and 95% confidence interval (95%CI) of serum and BALF GM tests used alone and in combination in the clinical diagnosis of IPA in non-neutropenic children were 29.0% (95%CI: 20.1%-37.9%), 75.0% (95%CI: 66.5%-83.5%) and 81.0% (95%CI: 73.3%-88.7%), respectively. The AUC and 95%CI were 0.645 (95%CI: 0.513-0.778), 0.785 (95%CI: 0.644-0.926) and 0.819 (95%CI: 0.681-0.953), respectively.Conclusions:The combined detection of serum and BALF GM was better than a single indicator in the clinical diagnosis of IPA in non-neutropenic children, suggesting the combined detection was of great value in clinical diagnosis.
5.Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles
Yimin ZHU ; Yue GAO ; Donghong NAI ; Linli HU ; Lei JIN ; Ying ZHONG ; Ze WU ; Guimin HAO ; Qiongfang WU ; Yichun GUAN ; Hong JIANG ; Cuilian ZHANG ; Minli LIU ; Xiaohong WANG ; Xiaoming TENG ; Jinliang DUAN ; Liran LI ; Yue ZHANG ; Hong YE
Chinese Journal of Obstetrics and Gynecology 2022;57(7):510-518
Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.
6.Predictive value of bioelectrical impedance analysis-measured body fat to abnormal lipid profiles in children and adolescents: the optimal cut-off values of body fat
Hong CHENG ; Haibo LI ; Dongqing HOU ; Aiyu GAO ; Zhongxin ZHU ; Zhaocang YU ; Hongjian WANG ; Xiaoyuan ZHAO ; Pei XIAO ; Guimin HUANG ; Jie MI
Chinese Journal of Applied Clinical Pediatrics 2021;36(1):36-41
Objective:To assess the predictive values of bioelectrical impedance analysis(BIA)-measured body fat indices to abnormal lipid profiles, and to preliminary propose optimal cut-off values of body fat in children and adolescents.Methods:Children and adolescents, aged 6-16 years, were selected from 30 schools (8 primary schools, 21 middle schools and one 12-year education school) in Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by adopting a stratified cluster sampling method from November 2017 to January 2018.Questionnaire survey, body mass index(BMI), body fat mass index (FMI), fat mass percentage (FMP) and four lipid profiles were conducted.Results:A total of 14 309 participants, aged (11.0±3.3) years, were enrolled in the analysis, with 49.9% boys.In boys and girls, the percentile values ( P60- P95) fitted by FMI and FMP with K-median-coefficient of variation(LMS) method were taken as the cutting points, and P75 values were selected as the cut-off points of excessive body fat for their better sensitivity, specificity, predictive value and area under curve (AUC) for identification of abnormal lipid profiles.Boys with FMI above P75 accounted for 28% of the total population, and controlling boys with FMI below P75 could prevent dyslipidemia of 8%-57%.FMI in girl population occupied about 26% of the above, and controlling FMI in girl population below this cut-off point may prevent dyslipidemia from 8%-42%.FMP observed similar results to FMI.Assessed by FMI or FMP with P75 cut-off values, adiposity performed better than BMI for recognizing abnormal lipid profiles in boys (AUC: 52.4%-69.6% vs.50.2%-67.1%, P<0.05) rather than in girls ( P>0.05). In addition, when FMI or FMP beyond P90, the specificity of each abnormal lipid profiles was around 90%. Conclusions:The recommend cut-off points for body fat may be to assess children′s adiposity, and can be applied in preventive activities.
7.Immunogenicity study on recombinant fHBP of meningococcal group B
Guimin SU ; Guocun JI ; Jing LONG ; Tong GUO ; Ying JI ; Hao CHEN ; Guangyuan DU ; Qidong XIAO ; Weihua ZHU ; Lin DU
Chinese Journal of Microbiology and Immunology 2021;41(5):368-373
Objective:To evaluate the immunogenicity of recombinant factor H binding protein(fHBP) by detecting serum antibody titer and serum bactericidal antibody test (SBA).Methods:fHBP sequence was selected and synthesized, connected to plasmid pET43.1a, transformed to Escherichia coli BL21(DE3), and expressed two recombinant fHBP proteins, included two subfamilies, fHBPA and fHBPB. After purification, the recombinant fHBP proteins were immunized to rabbits and mice. The immune antiserum titer and the bactericidal titer to epidemic strains of meningococcal bacteria group B were measured by ELISA and SBA respectively. Results:The antiserum titer of fHBP immunized rabbits was greater than 2.0×10 6, and that of immunized mice was not less than 1.0×10 6. fHBP immunized rabbit serum had bactericidal titer more than 1∶128 to 41 strains A subfamily and 20 strains B subfamily in the SBA against 69 endemic strains, and there was no cross-protection between the subfamily bacteria. The bactericidal titers of mouse serum immunized fHBPA to strains A subfamily such as Nm210902 Nm211009、Nm450522 were 1∶1 024, 1∶608、1∶861, to Nm510703、Nm311304、Nm431002 were 1∶234、1∶861、1∶430 respectively, and mouse serum immunized fHBP B to strains B subfamily Nm311302、Nm311304、Nm431002 were 1∶876、1∶274、1∶1858, all of three strains were positive in bactericidal titers. Conclusions:the titer of fHBP antiserum was higher than 1.0×10 6, the bactericidal titer was no less than 1∶128 to 61 epidemic strains, and it has a 94.2% protective effect on 69 meningococcal epidemic strains group B.
8.Change in obesity status and development of cardiometabolic disorders in school-age children
Dongqing HOU ; Hongbo DONG ; Zhongxin ZHU ; Zhaocang YU ; Hongjian WANG ; Aiyu GAO ; Hong CHENG ; Xiaoyuan ZHAO ; Junting LIU ; Guimin HUANG ; Fangfang CHEN ; Jie MI
Chinese Journal of Epidemiology 2021;42(3):440-447
Objective:To analyze the influence of obesity status on the development of cardiometabolic disorders in school-age children.Methods:Information about children's body weight, body height and cardiovascular risk factors were collected in baseline survey in 2017 and follow-up survey in 2019. The school-age children were divided into four groups based on their baseline and follow-up obesity status, i.e. sustained non-obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Analysis of covariance was used to compare the difference of change in levels of cardiometabolic factors among the four groups. The multivariate logistic regression model was used to analyze the relationship between obesity status and the incidence risk of cardiometabolic disorders.Results:The present study included 11 379 school-age children (boys accounting for 49.6%). During the 2 years, the incidence of obesity was 3.2% (95% CI: 2.9%-3.5%) with the restoration ratio of obesity of 4.4% (95% CI: 4.0%-4.8%). Compared with the sustained non-obesity group, increases in SBP, DBP, TG, LDL-C and non-HDL-C were much higher in newly classified obesity group and persistent obesity group, but lower in restored obesity groups except for DBP (all P<0.05). In addition, the incidence risk of hypertension, high glucose, dyslipidemia and cardiometabolic disorders (≥2 risks) were much higher in newly classified and persistent obese children than in sustained non-obese children. No difference was found in incidence risks of most cardiovascular disorders between restored obese children and sustained non-obese children, except for hypertension and cardiometabolic risks. Conclusion:Both newly classified obesity and persistent obesity increased the incidence risks for multi cardiovascular disorders, while these risks could be reduced when non-obese status restore.
9.One case of papillary carcinoma of thyroid following successful liver transplantation
Zhaohui ZHU ; Chang SU ; Weidong ZHOU ; Zhongying MIAO ; Guimin WANG
Chinese Journal of Endocrine Surgery 2020;14(5):436-438
The incidence of papillary thyroid cancer after liver transplantation is relatively low. This article introduces the treatment and prognosis of a case of papillary thyroid cancer after liver transplantation, and discusses the occurrence and development of thyroid cancer after liver transplantation and perioperative management and the prognosis, in order to further enhance the comprehensive management of such patients, extend the survival period and improve the quality of life.
10.Experimental study of IL-8 monoclonal antibody combined with ultrasound targeted microbubble destruction on myocardial ischemia/reperfusion injury in rabbits
Yue SUN ; Lirong XU ; Guimin ZHU ; Hanning YANG ; Lihong YANG ; Yongping LU
Chinese Journal of Ultrasonography 2019;28(1):77-82
Objective To explore the application value of IL-8 monoclonal antibody microbubble combined with ultrsound targeted microbubble destruction ( UTMD) on alleviating myocardial ischemia reperfusion/injury ( MIRI) in rabbits .Methods Forty-two rabbits were randomly divided into closed chest group ( n =7) ,open chest control group ( n = 7) and ischemia-reperfusion ( I/R) group ( n = 28) .I/R group were randomly divided into 30 min reperfusion group( n =7) ,60 min reperfusion group( n =7) ,120 min reperfusion group ( n = 7 ) and 180 min reperfusion group ( n = 7 ) .All rabbits were examined by electrocardiogram , echocardiography and HE staining after MIRI . Targeted myocardial contrast echocardiography ( MCE) was performed and ELISA was used to detect IL-8 content in rabbit myocardium before and after UTMD . Results Electrocardiogram and wall motion returned to normal at 60 min after reperfusion .Targeted MCE showed that with the prolongation of reperfusion after I/R ,the video intensity of myocardium in reperfusion area increased gradually , reaching its peak at 120 min and 180 min after reperfusion .After UTMD ,the video intensity decreased ,and the change rate of video intensity in 30 min reperfusion group was higher than those in other reperfusion groups(all P<0 .05) .The content of IL-8 and its neutralization rate in the ELISA results were consistent with the video intensity and rate of change of targeted MCE .HE staining and scanning electron microscopy showed that myocardial injury was found in I/R group .With the prolongation of reperfusion time ,the degree of myocardial injury was gradually aggravated ,and the injury was alleviated after irradiation .Conclusions IL-8 monoclonal antibody combined with UTMD has the advantages of non-invasive and highly effective in alleviating MIRI .It provides a new way to treat MIRI .

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