Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.

Dentatorubral-pallidoluysian atrophy（DRPLA） is a rare autosomal dominant neurodegenerative disease caused by CAG triplet expansion in the atrophin 1 （ATN1） gene. Up to now， the pathogenesis of DRPLA remains unclear. The main clinical features of DRPLA include myoclonus， epilepsy， ataxia， choreoathetosis， and cognitive impairment. DRPLA has great clinical heterogeneity， and the number of CAG repeats is negatively correlated with age of onset and disease severity. Some patients with late-onset DRPLA may have atypical manifestations without typical imaging changes， which brings challenges to the diagnosis of the disease. This article reviews the pathogenesis， pathological features， clinical and imaging manifestations， diagnosis， and potential treatment of DRPLA， in order to deepen the understanding of this disease.
Ataxia ; Myoclonus

The Inner Canon of Yellow Emperor （《黄帝内经》） constructs its theoretical system under the influence of the holistic， symbolic， and holographic mental models of traditional Chinese medicine （TCM）. It lays the theoretical foundation of TCM and provides a paradigm for TCM theory construction， serving as an original academic gene and theoretical source for the inheritance and innovation of modern TCM. Based on the theoretical paradigms derived from The Inner Canon of Yellow Emperor， the holistic mental model， the symbolic mental model， and the holographic mental model in shaping nature-human medicine theory， imagery-based theory， and fractal theory， this study revealed that TCM theory relies on the cognitive framework of traditional cultural mental models. On this basis， we proposed that the modern TCM mental model should return to its roots while fostering innovation， integrating tradition with modernity by combining macroscopic with microscopic perspectives， scientific with humanistic cognition， as well as evidence-based research with digital and artificial intelligence technologies. Furthermore， with a future-oriented approach， this paper discussed on the strategies for reshaping the modern TCM mental model from three dimensions of TCM diagnosis and treatment， TCM education， and TCM research， which could not only preserve the traditional clinical thinking characteristics of TCM， but also innovate modern TCM practice.

Objective To observe the value of self-made self-coagulating denture power helmet for PET/CT scanning of adult rats.Methods Eleven adult healthy male SD rats with body weight of 290-300 g were selected.Taken 1 rat's head as a reference,a self-made helmet with a thickness of 2 mm was obtained using self-coagulating denture powder to fix the rat's head.Then the other 10 rats were randomly divided into group A and group B(each n=5).The heads of rats were fixed with helmets,and 18F-FDG PET(scanning time 20 min)and CT images were acquired.Pain models were constructed using rats in group B through injection of 5％formaldehyde solution 0.10 ml at the right foot at the 11th minute during PET collection.The imaging quality of 18F-FDG PET/CT in group A was observed,and CT gray values of the olfactory bulb covered by helmet and soft tissue area posterior occipital region without helmet coverage in group A were compared.The quality of PET images before and after pain induction in group B were analyzed to evaluate the fixation effect of helmet.Based on PET images,the changes of 18F-FDG standard uptake value ratio(SUVR)in primary somatosensory cortex hindlimb region(S1HL)in group B after pain induction were observed.Results PET and CT images in group A were clear,with no obvious foreign body artifacts.CT gray values of olfactory bulb and soft tissue in posterior occipital region in group A was 257.0±50.7 and 194.4±55.4,respectively,being not significantly different(P=0.054).PET images before and after pain induction in group B showed no obvious artifacts,and the continuity between covered area of helmet and non-covered area was good.After pain induction,S1HL on the contralateral side of pain induction in group B significantly activated.The ratio of SUVRafter pain induction/SUVRbefore pain induction in S1HL on the contralateral side of pain induction was 1.19±0.07,and SUVRafter pain induction was higher than SUVRbefore pain induction(P=0.001).Conclusion Self-made self-coagulation denture powder helmet could effectively fix head of adult rat during PET/CT scanning.

Objective To observe the value of self-made self-coagulating denture power helmet for PET/CT scanning of adult rats.Methods Eleven adult healthy male SD rats with body weight of 290-300 g were selected.Taken 1 rat's head as a reference,a self-made helmet with a thickness of 2 mm was obtained using self-coagulating denture powder to fix the rat's head.Then the other 10 rats were randomly divided into group A and group B(each n=5).The heads of rats were fixed with helmets,and 18F-FDG PET(scanning time 20 min)and CT images were acquired.Pain models were constructed using rats in group B through injection of 5％formaldehyde solution 0.10 ml at the right foot at the 11th minute during PET collection.The imaging quality of 18F-FDG PET/CT in group A was observed,and CT gray values of the olfactory bulb covered by helmet and soft tissue area posterior occipital region without helmet coverage in group A were compared.The quality of PET images before and after pain induction in group B were analyzed to evaluate the fixation effect of helmet.Based on PET images,the changes of 18F-FDG standard uptake value ratio(SUVR)in primary somatosensory cortex hindlimb region(S1HL)in group B after pain induction were observed.Results PET and CT images in group A were clear,with no obvious foreign body artifacts.CT gray values of olfactory bulb and soft tissue in posterior occipital region in group A was 257.0±50.7 and 194.4±55.4,respectively,being not significantly different(P=0.054).PET images before and after pain induction in group B showed no obvious artifacts,and the continuity between covered area of helmet and non-covered area was good.After pain induction,S1HL on the contralateral side of pain induction in group B significantly activated.The ratio of SUVRafter pain induction/SUVRbefore pain induction in S1HL on the contralateral side of pain induction was 1.19±0.07,and SUVRafter pain induction was higher than SUVRbefore pain induction(P=0.001).Conclusion Self-made self-coagulation denture powder helmet could effectively fix head of adult rat during PET/CT scanning.

Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

This study intends to establish a colorectal cancer(CRC)organoid model,expand and isolate CRC-reactive tumor-infiltrating lymphocytes(TILs),screen tumor-specific T cell receptors(TCRs)and perform functional verification,in order to provide a technological platform and research foundation for the clinical transformation of individualized adoptive T-cell immunotherapy for colorectal cancer.An organoid model derived from colon cancer patient tissues was constructed using in vitro 3D culture techniques,which then subjected to HE staining and immunohistochemistry for detecting morphological characteristics and representative molecular expression.Subsequently,CRC organoids were co-cultured with TILs for sorting reactive TILs using flow cytometry,and the characteristics of reactive TCR clones was analyzed through single T cell receptor gene cloning technology.Furthermore,the function of TCRs was verified through cytotoxicity experiments.Morphological analysis and representative molecules(CK20 and CDX2)expression indicated that there is high similarity between colorectal cancer organoids and patient tumors.In the in vitro expanded and cultured TILs,colorectal cancer-reactive T cells with upregulated CD137 expression and increased IFN-γ secretion were screened out successfully,among which TCR2-T cells demonstrated superior tumor reactivity and in vitro tumor killing function.In conclusion,a platform for screening and function validation of reactive TCRs based on CRC-Org has been established,providing a technological platform for the translational application of individualized T-cell therapy for colorectal cancer.

Objective:This study aimed to compare the efficacy and safety between high-dose intravenous iron and oral iron in treating iron deficiency anemia (IDA) .Methods:This prospective randomized controlled study (1∶1) enrolled 338 patients with IDA at The First Affiliated Hospital of Soochow University, Suzhou Hongci Hematology Hospital, and Huai’an Second People’s Hospital from June 1, 2022, to January 19, 2024. Of all the patients, 169 received high-dose intravenous iron therapy and 169 received oral iron treatment for 12 weeks of observation. Focus on the hemoglobin (HGB) change from baseline to week 4, secondary focus was on the HGB and iron metabolism parameters (serum iron [SI], transferrin saturation [TSAT], total iron binding force [TIBC], serum ferritin [SF]), and changes in the fatigue score, efficacy, and treatment-related adverse effects were monitored throughout in the two treatment groups.Results:The HGB levels were improved in both treatments, but the HGB improved faster in the intravenous group compared with the oral group. HGB increased from (76.8±15.0) g/L to (118.0±13.3) g/L in the intravenous group and from (77.9±11.6) g/L to (104.3±15.0) g/L in the oral group after 4 weeks of treatment. The increase from baseline in the intravenous group (40.7±17.3) g/L was significantly higher than that in the oral group (27.2±17.5) g/L ( P<0.001). The intravenous group demonstrated a more significant early effect than the oral group in terms of iron metabolism parameter improvement. SI, TSAT, TBIC, and SF increased better from baseline at 4 weeks in the intravenous group than in the oral group ( P<0.001). Additionally, the intravenous group exhibited better fatigue scores for early improvement than the oral group ( P<0.001). The incidence of total adverse effects was similar in the intravenous group as compared to the oral group (3.5% [6/169] vs 5.9% [10/169], P=0.442) . Conclusion:High doses of intravenous iron quickly boost HGB early, causing rapid improvement in SI, TSAT, TBIC, SF, and patient fatigue scores. The patient was well tolerated.

Objective:This study aimed to compare the efficacy and safety between high-dose intravenous iron and oral iron in treating iron deficiency anemia (IDA) .Methods:This prospective randomized controlled study (1∶1) enrolled 338 patients with IDA at The First Affiliated Hospital of Soochow University, Suzhou Hongci Hematology Hospital, and Huai’an Second People’s Hospital from June 1, 2022, to January 19, 2024. Of all the patients, 169 received high-dose intravenous iron therapy and 169 received oral iron treatment for 12 weeks of observation. Focus on the hemoglobin (HGB) change from baseline to week 4, secondary focus was on the HGB and iron metabolism parameters (serum iron [SI], transferrin saturation [TSAT], total iron binding force [TIBC], serum ferritin [SF]), and changes in the fatigue score, efficacy, and treatment-related adverse effects were monitored throughout in the two treatment groups.Results:The HGB levels were improved in both treatments, but the HGB improved faster in the intravenous group compared with the oral group. HGB increased from (76.8±15.0) g/L to (118.0±13.3) g/L in the intravenous group and from (77.9±11.6) g/L to (104.3±15.0) g/L in the oral group after 4 weeks of treatment. The increase from baseline in the intravenous group (40.7±17.3) g/L was significantly higher than that in the oral group (27.2±17.5) g/L ( P<0.001). The intravenous group demonstrated a more significant early effect than the oral group in terms of iron metabolism parameter improvement. SI, TSAT, TBIC, and SF increased better from baseline at 4 weeks in the intravenous group than in the oral group ( P<0.001). Additionally, the intravenous group exhibited better fatigue scores for early improvement than the oral group ( P<0.001). The incidence of total adverse effects was similar in the intravenous group as compared to the oral group (3.5% [6/169] vs 5.9% [10/169], P=0.442) . Conclusion:High doses of intravenous iron quickly boost HGB early, causing rapid improvement in SI, TSAT, TBIC, SF, and patient fatigue scores. The patient was well tolerated.