1.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
2.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
3.Relationship between gut microbiota and onset of depression in chronic unpredictable mild stress model rats of both sexes
Kanghong ZHU ; Yumeng GAO ; Mengxue HUANG ; Liu YANG ; Zizhan GAO ; Hao CHU ; Nan DENG ; Ling HU ; Zijian WU
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1144-1152
Objective To observe the differences in gut microbiota in chronic unpredictable mild stress(CUMS)-induced depression model rats of both sexes,and to provide experimental evidence for exploring sex differences in depression onset.Methods Thirty-two healthy SD rats were divided randomly into four groups based on sex:Male control group(Control-M),Female control group(Control-F),Male model group(Model-M),and Female model group(Model-F)(n=8 rats per group).Rats in the control groups were fed without stimulation,while rats in the model groups were stimulated using the 28 d CUMS-induced depression method.After successful modeling,fresh feces were collected from all rats for high-throughput 16S rRNA sequencing.Behavioral observations were also conducted before and after preparing the model.Results The result of sucrose-preference,open-field,and forced-swimming tests differed significantly between the control and model groups.The result of the sucrose-preference test also differed between the sexes,while there was no difference in the open-field or forced-swimming test between the sexes.The α and β diversity of the gut microbiota genera showed an upward trend in the CUMS group compared with the control group.The ratio of Firmicutes/Bacteroidetes and the richness of the Roseburia and Lachnospiraceae_NK4A136_group were decreased in male rats but showed an increasing trend in female rats.Conclusions The ratio of Firmicutes/Bacteroidetes in the gut microbiota may be a key factor affecting the difference in the onset of depression between males and females,while the Roseburia and Lachnospiraceae_NK4A136_group be potential factors in correcting the gut microbiota and improving the symptoms of depression.
4.A case of epstein-barr virus positive nasopharyngeal large cell neuroendocrine carcinoma and literature review
Journal of Chinese Physician 2025;27(2):257-260
Objective:To share the diagnosis and treatment of a case of epstein-barr virus positive nasopharyngeal large cell neuroendocrine carcinoma.Methods:The clinical data of a patient with epstein-barr virus positive nasopharyngeal large cell neuroendocrine carcinoma admitted to the Third Xiangya Hospital of Central South University in October 2020 were retrospectively analyzed, and the literature was reviewed to analyze the characteristics of the case, distinguish it from similar cases, and summarize the diagnosis experience.Results:The patient, a 53 year old male, was diagnosed with large cell neuroendocrine carcinoma after imaging examination revealed a mass of the nasopharynx. The patient underwent endoscopic excisional biopsy of the mass, and microscopic examination, immunohistochemistry, and in-situ hybridization for EBV were performed.Conclusions:Large cell neuroendocrine carcinoma expresses markers of pancytokeratins (CK), synaptophysin (Syn), chromogranin A (CgA), and nerve cell adhesion molecule (CD56). When morphologically considered as large cell neuroendocrine carcinoma, ancillary findings including immune markers and in-situ hybridization for EBV support the diagnosis of EBV-positive large cell NEC, and the treatment regimen is mainly-followed by radiotherapy and chemotherapy.
5.The effect of Qing-Xin-Jie-Yu Granule on arteriovenous bypass thrombosis formation and ADP-induced platelet aggregation in rats
Chenchen HE ; Jianghan QI ; Chenyi WEI ; Qiaoyan CAI ; Zhuye GAO ; Ling ZHANG ; Jianfeng CHU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):184-189
Objective To observe the effect of Qing-Xin-Jie-Yu granule(QXJYG)on the formation of thrombosis in the rat model of arteriovenous bypass thrombosis and the adenosine diphosphate(ADP)-induced platelet aggregation.Methods Thirty-six male SD rats were randomly divided into normal control group,model group,clopidogrel positive control group,QXJYG low-dose,medium-dose and high-dose groups,with 6 rats in each group.The dose of clopidogrel positive control group was 6.74 mg/(kg?d),the dosages of QXJYG in low,medium and high groups were 0.99,1.98,3.96 g/(kg?d),respectively,normal control group and model group were given equal volume of distilled water,and continuous prophylactic intragastric administration for 14 days,once a day.One hour after the final administration,the rats were anesthetized,and the arteriovenous bypass thrombosis model was established by using a polyethylene tube as the arteriovenous bypass bridge(except control group).The thrombus was extracted after 15 min and its weight was weighed by 1/10,000th precision electronic balance.The levels of thromboxane B2(TXB2)and 6-keto-prostaglandin F1α(6-keto-PGF1α)in plasma were determined by ELISA kits.The rate of platelet aggregation induced by ADP in each group was measured using a microplate reader by turbidimetric method.Results Compared with the control group,the weight of arteriovenous bypass thrombus was significantly higher,the level of TXB2 in plasma was significantly higher,while the level of 6-keto-PGF1α was significantly lower,and platelet aggregation was significantly higher after ADP induction in the model group(P<0.05).Compared with the model group,the weight of arteriovenous bypass thrombosis in clopidogrel positive control group and QXJYG dose groups was significantly decreased(P<0.05);the inhibition rate of thrombosis formation was 53.80%,23.96%,33.63%,and 32.59%,respectively.The content of TXB2 in plasma was significantly decreased,the content of 6-keto-PGF1α was significantly increased;additionally,the platelet aggregation rate induced by ADP was reduced in clopidogrel positive control group and QXJYG group.Meanwhile,there was a dose-dependence between different doses in QXJYY group(P<0.05),and the inhibition rate of platelet aggregation was 86.90%,26.17%,38.87%,54.48%,respectively.Conclusion QXJYG can prevent thrombosis formation in the rat model of arteriovenous bypass thrombosis and inhibit platelet aggregation induced by ADP.
6.Construction and evaluation of a cell model simulating the change of testicular microenvironment mediated by hypoxic and high-pressure conditions in varicocele mice
Shu-lin LIANG ; Li-guo GENG ; Ling HAN ; Chu-nan RONG ; Zhan QIN ; Juan DU ; Chao-ba HE ; Shao-ying YUAN
National Journal of Andrology 2025;31(6):483-491
Objective:Varicocele(VC)induces male infertility by mediating changes in the testicular microenvironment,in which testicular hypoxia and high-pressure are important pathological conditions.This study aims to compare the mouse spermatogenesis(GC-2spd)cells and Sertoli(TM4)cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling,and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model.Methods:On the basis of cell hypoxia induced by CoCl2,the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution.After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model,the cells were divided into normal group,hypoxia model group and composite model group.And the levels of OS,programmed cell death,inflammatory factors,and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods.Results:The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L,respectively,and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg(P<0.05).Compared with the normal group,the SOD levels of GC-2 and TM4 cells decreased(all P<0.05),CAT level decreased(all P<0.05),and MDA level increased(all P<0.01),and the OS level of GC-2 and TM4 cells was more obvious than that of the hy-poxia model group(all P<0.05).Compared with the normal group,apoptosis occurred in GC-2 and TM4 cells after composite model-ing(all P<0.05).Compared with the normal group,the mRNA expressions of IL-1β,IL-18,TNF-α and COX-2 in GC-2 and TM4 cells significantly increased(P<0.01)and higher than those in hypoxia model group(P<0.05)and induced pyroptosis(P<0.01).The expression level of GSDMD increased(P<0.05).Conclusion:The cell model with hypoxia and high pressure com-bined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone,but also further cause in-flammatory response damage and pyroptosis,which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC.This cell model can be used for studying the pathogenesis of VC-associated male infertility,evalu-ating drug efficacy,and exploring pharmacological mechanisms.
7.Clinical Analysis of Torque Teno Virus Infection after Hematopoi-etic Stem Cell Transplantation in Children
Ye-Ping SHENG ; Ling-Jun KONG ; Pei-Pei CHU ; Ya-Lin XIA ; Chen-Tao SHEN ; Jie-Fan SUN
Journal of Experimental Hematology 2025;33(6):1784-1789
Objective:To investigate the incidence,clinical characteristics,and complications of Torque teno virus(TTV)in children after hematopoietic stem cell transplantation(HSCT).Methods:A total of 40 children with hematological diseases who underwent HSCT were selected,and metagenomic next-generation sequencing(mNGS)technology was used to detect the gene sequences of pathogenic microorganisms in the blood.Combined with clinical data,the characteristics of TTV infection were analyzed.Results:Among the 40 pediatric patients post-HSCT,the TTV positive rate was 42.5%(17/40).There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex,age,white blood cell count(WBC),red blood cell count(RBC),hemoglobin,platelet count,neutrophil count,lymphocyte count,and high-sensitivity C-reactive protein(all P>0.05).The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells(BMSC)as the transplant source(P<0.05).However,there were no significant differences in the TTV infection rate among patients with different disease types,different HLA matching statuses,or different engraftment times of neutrophils and platelets(all P>0.05).Among 17 children infected with TTV,13(76.5%)had co-infections with other viruses,mainly including cytomegalovirus(58.8%,10/17),human polyomavirus(41.2%,7/17),and Epstein-Barr virus(17.6%,3/17).In children with TTV infection,the most common complications were sepsis(82.4%),graft-versus-host disease(GVHD)(70.6%),pulmonary infection(41.2%),and hemorrhagic cystitis(17.6%).The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group(P<0.05).Conclusion:TTV infection is common in children undergoing HSCT,and it is prone to be complicated with cytomegalovirus infection and GVHD,which has an important influence on the clinical outcomes.
8.Efficacy and Safety of Polatuzumab Vedotin Combined with Chemotherapy in the Treatment of Relapsed and Refractory Diffuse Large B-Cell Lymphoma
Ke-Ting JIN ; Jin-Dan XIA ; Chu-Yun QIAN ; Qian ZHANG ; Qian JIANG ; Song-Di CHEN ; Wei-Ze ZHANG ; Lu-Ling MAO ; Yi ZHAO
Journal of Experimental Hematology 2025;33(6):1617-1622
Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.
9.Assessment of Genotoxicity of Tissue Engineered Materials Based on Improved in vivo Hepatocyte Unscheduled DNA Synthesis(UDS)Assay
Luan-luan WANG ; Li HOU ; Xiang-yu CHU ; Zi-yi YANG ; Ling-xiao SUN ; Xiao-fei WANG ; Qiu-jin QU ; Jing XU ; Zeng-xiang LIU ; Xiao-xia SUN
Progress in Modern Biomedicine 2025;25(17):2740-2748
Objective:An in vivo mammalian hepatocyte Unscheduled DNA Synthesis(UDS)test was used to evaluate the genotoxicity of Cross-linked Sodium Hyaluronate Gel and Bone Repair Materials,providing experimental evidence for establishing a UDS testing method for medical devices and materials.Methods:0.9%sodium chloride injection and cottonseed oil were used as the solvent for test materials and negative control,respectively.N-dimethylnitrosamine(NDMA)was used as the positive control for the early sampling times,and 2-acetylaminofluorene(2-AAF)was used as the positive control for the late sampling times.SD rats were administered a single dose for toxic exposure,and liver tissues were collected at 4 h and 16 h,respectively.Hepatocytes were isolated using collagenase perfusion.After labeling with 5-ethynyl-2'-deoxyuridine(EdU),and the net average fluorescence intensity(NAFI)of cell nuclei and nucleoplasm was measured by fluorescence microscope.Data from 50 cells were used to analyze the DNA repair level.Results:Compared with the negative control groups,the positive control groups(NDMA and 2-AAF)showed highly statistically significant differences in NAFI(P<0.01),indicating successful induction of DNA damage.There was no statistically significant differences between the cross-linked sodium hyaluronate gel groups,bone repair material groups and the negative control group(P>0.05),suggesting that these materials did not significantly induce DNA damage under the experimental conditions.Conclusion:This study first applied EdU labeling technology to the in vivo hepatic UDS assay,achieving non-radioactive labeling through click chemistry reactions.Under the conditions of this study,cross-linked sodium hyaluronate gel and bone repair materials did not exhibit genotoxicity.In the follow-up,the sample range can be expanded and the observation period can be prolonged to further improve the genotoxicity evaluation system of medical devices.
10.The effect of Qing-Xin-Jie-Yu Granule on arteriovenous bypass thrombosis formation and ADP-induced platelet aggregation in rats
Chenchen HE ; Jianghan QI ; Chenyi WEI ; Qiaoyan CAI ; Zhuye GAO ; Ling ZHANG ; Jianfeng CHU
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):184-189
Objective To observe the effect of Qing-Xin-Jie-Yu granule(QXJYG)on the formation of thrombosis in the rat model of arteriovenous bypass thrombosis and the adenosine diphosphate(ADP)-induced platelet aggregation.Methods Thirty-six male SD rats were randomly divided into normal control group,model group,clopidogrel positive control group,QXJYG low-dose,medium-dose and high-dose groups,with 6 rats in each group.The dose of clopidogrel positive control group was 6.74 mg/(kg?d),the dosages of QXJYG in low,medium and high groups were 0.99,1.98,3.96 g/(kg?d),respectively,normal control group and model group were given equal volume of distilled water,and continuous prophylactic intragastric administration for 14 days,once a day.One hour after the final administration,the rats were anesthetized,and the arteriovenous bypass thrombosis model was established by using a polyethylene tube as the arteriovenous bypass bridge(except control group).The thrombus was extracted after 15 min and its weight was weighed by 1/10,000th precision electronic balance.The levels of thromboxane B2(TXB2)and 6-keto-prostaglandin F1α(6-keto-PGF1α)in plasma were determined by ELISA kits.The rate of platelet aggregation induced by ADP in each group was measured using a microplate reader by turbidimetric method.Results Compared with the control group,the weight of arteriovenous bypass thrombus was significantly higher,the level of TXB2 in plasma was significantly higher,while the level of 6-keto-PGF1α was significantly lower,and platelet aggregation was significantly higher after ADP induction in the model group(P<0.05).Compared with the model group,the weight of arteriovenous bypass thrombosis in clopidogrel positive control group and QXJYG dose groups was significantly decreased(P<0.05);the inhibition rate of thrombosis formation was 53.80%,23.96%,33.63%,and 32.59%,respectively.The content of TXB2 in plasma was significantly decreased,the content of 6-keto-PGF1α was significantly increased;additionally,the platelet aggregation rate induced by ADP was reduced in clopidogrel positive control group and QXJYG group.Meanwhile,there was a dose-dependence between different doses in QXJYY group(P<0.05),and the inhibition rate of platelet aggregation was 86.90%,26.17%,38.87%,54.48%,respectively.Conclusion QXJYG can prevent thrombosis formation in the rat model of arteriovenous bypass thrombosis and inhibit platelet aggregation induced by ADP.

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