1.Effect of Stattic on the survival of mouse heart allograft by regulating memory CD4+T cell-mediated acute rejection
Shiliang LI ; Yi FENG ; Ming FANG ; Yan ZHOU
Organ Transplantation 2025;16(1):74-82
Objective To investigate the effect and mechanism of the signal transducer and activator of transcription 3 (STAT3) inhibitor Stattic on the rejection of mouse heart allograft. Methods BALB/c mice (donors) were used to transplant skin onto C57BL/6 mice (recipients). Four weeks later, memory CD4+ T cells (CD4+Tm) were isolated from the recipient mice's spleens. Mixed lymphocyte reaction experiment was conducted with C57BL/6 mouse splenocytes and CD4+Tm, and the EdU method was used to detect the effect of Stattic on CD4+Tm cell proliferation. A C57BL/6 mouse heart transplant (HTx) model was constructed, and the experiment was divided into four groups: Non-HTx group, HTx group, Tm/HTx group, and Tm/HTx+Stattic group. The survival of heart allografts in mice was observed daily. Hematoxylin-eosin staining was used to observe the histopathology of the heart allografts. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-10, and transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) in the heart allografts. Enzyme-linked immunosorbent assay was used to detect the levels of IFN-γ, IL-2, IL-10, and TGF-β1 in the serum. Flow cytometry was used to detect the levels of CD4+Tm (CD4+CD44+CD62L+) in splenic lymphocytes. And Western blotting was used to detect the expression levels of STAT3 and p-STAT3 proteins in the heart allografts. Results When the concentration of Stattic exceeded 2.5 μmol/L, it could inhibit the proliferation of CD4+Tm cells. Compared with the HTx group, the Tm/HTx group showed shorter survival time of heart grafts, more severe histopathological damage, increased serum IFN-γ and IL-2 levels, decreased IL-10 and TGF-β1 levels, increased relative expression of IFN-γ and IL-2 mRNA, decreased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, increased proportion of CD4+Tm in splenic lymphocytes, and increased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Compared with the Tm/HTx group, the Tm/HTx+Stattic group showed longer survival time of heart grafts, less severe histopathological damage, decreased serum IFN-γ and IL-2 levels, increased IL-10 and TGF-β1 levels, decreased relative expression of IFN-γ and IL-2 mRNA, increased relative expression of IL-10 and TGF-β1 mRNA in the heart allografts, decreased proportion of CD4+Tm in splenic lymphocytes, and decreased p-STAT3/STAT3 ratio in the heart allografts (all P<0.05). Conclusions Stattic may prolong the survival time of mouse heart allografts, and its mechanism may be related to the inhibition of CD4+Tm- mediated acute rejection.
2.Analysis of characteristics of adverse drug reactions in a hospital from 2021 to 2023
Yan WANG ; Ming FANG ; Hongwei SONG ; Chao ZHONG ; Feng XU ; Ting ZHOU
Journal of Pharmaceutical Practice and Service 2025;43(4):200-204
Objective To analyze the characteristics of adverse drug reactions (ADR) reported in Sixth People’s Hospital South Campus, Shanghai Jiaotong University from 2021 to 2023, to provide reference for promoting rational clinical drug use. Methods ADR data reported in our hospital were collected retrospectively, including patients’ basic information, drugs causing adverse reactions, types of adverse reactions and outcomes. Descriptive analysis methods were used to summarize and analyze the data. Results A total of 979 cases of ADR were reported in our hospital from 2021 to 2023. The highest proportion of patients with ADR occurred in the age range of 31 to 50, and more male patients (63.5%). The top five drugs involved with adverse reactions were antibiotics (48.8%), Chinese medicine injections(19.2%), vitamins(7.5%), Chinese traditional medicine(7.2%), equine tetanus immunoglobulin(6.3%). Among antibiotics, cefuroxime, ceftazidime and cefotiam were the majority. The organs/systems involved in all ADR were mainly skin and accessories damage (55.4%). The clinical manifestations were rash, itching, and maculopapular rash. Conclusion From 2021 to 2023, the most common drugs causing adverse drug reactions in our hospital were mainly antibacterial drugs, and the rational clinical use of antibacterial drugs still needs to be concerned.
3.Temporal trend in mortality due to congenital heart disease in China from 2008 to 2021.
Youping TIAN ; Xiaojing HU ; Qing GU ; Miao YANG ; Pin JIA ; Xiaojing MA ; Xiaoling GE ; Quming ZHAO ; Fang LIU ; Ming YE ; Weili YAN ; Guoying HUANG
Chinese Medical Journal 2025;138(6):693-701
BACKGROUND:
Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China.
METHODS:
We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model.
RESULTS:
From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%).
CONCLUSIONS
CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans
;
Heart Defects, Congenital/mortality*
;
Male
;
Female
;
China/epidemiology*
;
Infant
;
Child, Preschool
;
Adult
;
Child
;
Adolescent
;
Infant, Newborn
;
Middle Aged
;
Young Adult
;
Aged
;
Rural Population
4.Review of chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex and prediction of its Q-markers.
Meng-Fan PENG ; Bao-Song LIU ; Pei-Pei YAN ; Cai-Xia LI ; Xiao-Fang ZHANG ; Yi ZHENG ; Ya-Gang SONG ; Tong LIU ; Lei YANG ; Ming-San MIAO
China Journal of Chinese Materia Medica 2025;50(4):946-958
Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Quality Control
;
Humans
;
Animals
5.Genetic diversity analysis and DNA fingerprinting of Artemisia argyi germplasm resources based on EST-SSR molecular markers.
Yu-Yang MA ; Chang-Jie CHEN ; Ming-Xing WANG ; Yan FANG ; Yu-Huan MIAO ; Da-Hui LIU
China Journal of Chinese Materia Medica 2025;50(9):2356-2364
This study investigates the genetic diversity and evolutionary relationships of different Artemisia argyi germplasm resources to provide a basis for germplasm identification, variety selection, and resource protection. A total of 192 germplasm resources of A. argyi were studied, and EST-based simple sequence repeat(EST-SSR) primers were designed based on transcriptomic data of A. argyi. Polymerase chain reaction(PCR) amplification was performed on these resources, followed by fluorescence capillary electrophoresis to detect genetic diversity and construct DNA fingerprints. From 197 pairs of primers designed, 28 pairs with polymorphic and clear bands were selected. A total of 278 alleles were detected, with an average of 9.900 0 alleles per primer pair and an average effective number of alleles of 1.407 2. The Shannon's diversity index(I) for the A. argyi germplasm resources ranged from 0.148 1 to 0.418 0, with an average of 0.255 7. The polymorphism information content(PIC) ranged from 0.454 5 to 0.878 0, with an average of 0.766 9, showing high polymorphism. Cluster analysis divided the A. argyi germplasm resources into three major groups: Group Ⅰ contained 136 germplasm samples, Group Ⅱ contained 45, and Group Ⅲ contained 11. Principal component analysis also divided the resources into three groups, which was generally consistent with the clustering results. Mantel test results showed that the genetic variation in A. argyi populations was to some extent influenced by geographic distance, but the effect was minimal. Structure analysis showed that 190 germplasm materials had Q≥ 0.6, indicating that these germplasm materials had a relatively homogeneous genetic origin. Furthermore, 8 core primer pairs were selected from the 28 designed primers, which could distinguish various germplasm types. Using these 8 core primers, DNA fingerprints for the 192 A. argyi germplasm resources were successfully constructed. EST-SSR molecular markers can be used to study the genetic diversity and phylogenetic relationships of A. argyi, providing theoretical support for the identification and molecular-assisted breeding of A. argyi germplasm resources.
Artemisia/classification*
;
Microsatellite Repeats
;
Genetic Variation
;
Expressed Sequence Tags
;
DNA Fingerprinting
;
Phylogeny
;
Polymorphism, Genetic
;
DNA, Plant/genetics*
;
Genetic Markers
6.Molecular targeted therapy for progressive low-grade gliomas in children.
Yan-Ling SUN ; Miao LI ; Jing-Jing LIU ; Wen-Chao GAO ; Yue-Fang WU ; Lu-Lu WAN ; Si-Qi REN ; Shu-Xu DU ; Wan-Shui WU ; Li-Ming SUN
Chinese Journal of Contemporary Pediatrics 2025;27(6):682-689
OBJECTIVES:
To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG).
METHODS:
A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed.
RESULTS:
Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group.
CONCLUSIONS
Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans
;
Glioma/genetics*
;
Male
;
Female
;
Child
;
Child, Preschool
;
Retrospective Studies
;
Brain Neoplasms/genetics*
;
Molecular Targeted Therapy/adverse effects*
;
Adolescent
;
Infant
;
Proto-Oncogene Proteins B-raf/genetics*
;
Pyrimidinones/therapeutic use*
;
Mutation
7.Clinical Features, Prognostic Analysis and Predictive Model Construction of Central Nervous System Invasion in Peripheral T-Cell Lymphoma.
Ya-Ting MA ; Yan-Fang CHEN ; Zhi-Yuan ZHOU ; Lei ZHANG ; Xin LI ; Xin-Hua WANG ; Xiao-Rui FU ; Zhen-Chang SUN ; Yu CHANG ; Fei-Fei NAN ; Ling LI ; Ming-Zhi ZHANG
Journal of Experimental Hematology 2025;33(3):760-768
OBJECTIVE:
To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion.
METHODS:
Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively.
RESULTS:
The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984).
CONCLUSION
The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans
;
Lymphoma, T-Cell, Peripheral/pathology*
;
Prognosis
;
Retrospective Studies
;
Central Nervous System Neoplasms/pathology*
;
Neoplasm Invasiveness
;
Male
;
Female
;
Central Nervous System/pathology*
;
Middle Aged
;
Adult
8.Analysis of Risk Factors for Mortality of Children with Severe Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation.
Yan CHEN ; Hao XIONG ; Zhi CHEN ; Na SONG ; Li YANG ; Fang TAO ; Li YANG ; Zhuo WANG ; Yu DU ; Ming SUN
Journal of Experimental Hematology 2025;33(3):886-891
OBJECTIVE:
To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA).
METHODS:
The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death.
RESULTS:
Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×109/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality.
CONCLUSION
Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×109/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans
;
Anemia, Aplastic/therapy*
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Risk Factors
;
Retrospective Studies
;
Child
;
Transplantation, Homologous
;
Male
;
Female
;
Graft vs Host Disease
;
Child, Preschool
;
Proportional Hazards Models
;
Adolescent
;
Infant
9.Divergent activation patterns of BRS3 revealed by two Chinese herb-derived agonists.
Jie LI ; Changyao LI ; Qingtong ZHOU ; Wei HAN ; Mingzhu FANG ; Youwei XU ; Yiting MAI ; Yao ZHANG ; Jiahua CUI ; H Eric XU ; Yan ZHANG ; Wanchao YIN ; Ming-Wei WANG
Acta Pharmaceutica Sinica B 2025;15(10):5231-5243
Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-Gq complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.
10.IsoVISoR: Towards 3D Mesoscale Brain Mapping of Large Mammals at Isotropic Sub-micron Resolution.
Chao-Yu YANG ; Yan SHEN ; Xiaoyang QI ; Lufeng DING ; Yanyang XIAO ; Qingyuan ZHU ; Hao WANG ; Cheng XU ; Pak-Ming LAU ; Pengcheng ZHOU ; Fang XU ; Guo-Qiang BI
Neuroscience Bulletin 2025;41(2):344-348

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