OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective:To investigate the association of the interaction and combined effect of renal function and body mass index (BMI) with the risk for all-cause death in patients with type 2 diabetes mellitus (T2DM) in communities of Jiangsu Province.Methods:The study subjects were from the Comprehensive Research Project of Diabetes Prevention and Control conducted in Jiangsu from December 2013 to January 2014, and follow up was conducted for them until September 30, 2023. A total of 20 025 subjects were included in the study. Cox proportional hazards regression model was used to analyze the association of renal function with risk for death in T2DM patients, and the association of interaction between renal function and BMI and their combined effect with all-cause death risk in T2DM patients.Results:In the follow up for 198 370 person-years, a total of 4 459 deaths were recorded. Cox proportional hazards regression model analysis showed that renal dysfunction was associated with 71% risk of all-cause mortality in all T2DM patients [hazard ratio ( HR) =1.71, 95% CI: 1.59-1.84], as well as in all BMI subgroups. Likelihood ratio test indicated an interaction between renal function and BMI (interaction for P=0.030). Compared with patients with normal renal function and normal BMI, those with normal renal function and over weight or obesity had a lower risk of all-cause mortality, and those with renal dysfunction and low weight had the highest risk for death ( HR=2.78, 95% CI: 1.87-4.14). Conclusions:There is association of interaction between renal function and BMI with all-cause mortality in T2DM patients. T2DM patients with renal dysfunction and low body weight had significant higher risk for death.

Objective:To investigate the association of the interaction and combined effect of renal function and body mass index (BMI) with the risk for all-cause death in patients with type 2 diabetes mellitus (T2DM) in communities of Jiangsu Province.Methods:The study subjects were from the Comprehensive Research Project of Diabetes Prevention and Control conducted in Jiangsu from December 2013 to January 2014, and follow up was conducted for them until September 30, 2023. A total of 20 025 subjects were included in the study. Cox proportional hazards regression model was used to analyze the association of renal function with risk for death in T2DM patients, and the association of interaction between renal function and BMI and their combined effect with all-cause death risk in T2DM patients.Results:In the follow up for 198 370 person-years, a total of 4 459 deaths were recorded. Cox proportional hazards regression model analysis showed that renal dysfunction was associated with 71% risk of all-cause mortality in all T2DM patients [hazard ratio ( HR) =1.71, 95% CI: 1.59-1.84], as well as in all BMI subgroups. Likelihood ratio test indicated an interaction between renal function and BMI (interaction for P=0.030). Compared with patients with normal renal function and normal BMI, those with normal renal function and over weight or obesity had a lower risk of all-cause mortality, and those with renal dysfunction and low weight had the highest risk for death ( HR=2.78, 95% CI: 1.87-4.14). Conclusions:There is association of interaction between renal function and BMI with all-cause mortality in T2DM patients. T2DM patients with renal dysfunction and low body weight had significant higher risk for death.

Objective:To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients.Methods:The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio ( HR) and 95% CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results:During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke ( HR=0.95, 95% CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke ( HR=1.05, 95% CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase: HR=1.17, 95% CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion:The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.

To investigate the associations of serum gamma-glutamyl transferase (GGT) levels with the risk of cardiovascular disease (CVD) and its subtypes in patients with type 2 diabetes mellitus (T2DM) in Jiangsu Province.Methods:The participants were enrolled in the Comprehensive Research project regarding 'Prevention and Control of Diabetes' in Jiangsu Province. The baseline survey was conducted from 2013 to 2014, and follow-up until December 31, 2021. After excluding the participants who self-reported with chronic liver disease/stroke/coronary heart disease at baseline survey and those with incomplete information on GGT, a total of 16 147 T2DM patients were included in the final analysis. Cox proportional hazard regression models were used to calculate the hazard ratio ( HR) and their 95% CI of GGT for CVD, myocardial infarction, and stroke. Restricted cubic spline models were applied to analyze the dose-response relationship between GGT and the risk of CVD and its subtypes. Results:During the median follow-up time of 8.02 years, 2 860 CVD cases were registered, including 196 cases of myocardial infarction and 2 730 cases of stroke. Multivariate Cox proportional risk regression model indicated that compared to the lowest serum GGT level group, the highest GGT level group had a 24% increased risk of CVD ( HR=1.24, 95% CI: 1.09-1.41) and a 23% increased risk of stroke ( HR=1.23, 95% CI: 1.08-1.40). The restricted cubic spline model showed a nonlinear dose-response relationship between GGT and the risk of CVD, myocardial infarction, and stroke in T2DM patients. Conclusions:High levels of GGT may be associated with an increased risk of cardiovascular disease in T2DM patients, which needs further exploration and validation in future clinical practice.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( ¹⁸F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL. METHODS: A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and ¹⁸F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of ¹⁸F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described. RESULTS: The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively. CONCLUSION ¹⁸F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Fluorodeoxyglucose F18 ; Bone Marrow/pathology* ; Retrospective Studies ; Positron-Emission Tomography/methods* ; Lymphoma, Large B-Cell, Diffuse/pathology*

This article focused on the significant public health issue of comorbidities in the elderly population and highlighted the important role of traditional Chinese medicine(TCM) in the prevention and treatment of comorbidities in the elderly. It suggested that TCM should fully utilize its advantages in holistic perspective, syndrome differentiation and treatment, and preventive medicine in the process of preventing and treating comorbidities in the elderly. At the same time, in response to the significant shift in the disease spectrum of the elderly, the increasingly innovative concepts in diagnosis and treatment, the growing demand for proactive health by the el-derly population, and the current emphasis on patient-centered evaluation standards, it is necessary to further conduct basic theoretical and experimental research on comorbidities in the elderly using TCM, emphasize clinical research on comorbidities in the elderly, explore appropriate efficacy evaluation systems, improve TCM prevention and treatment strategies and comprehensive intervention programs for comorbidities in the elderly, and leverage the unique role of TCM in the rehabilitation of elderly comorbidity patients. By analyzing the potential of TCM in the field of comorbidities in the elderly, this article is expected to provide new insights for future clinical practice and scientific research.
Aged ; Humans ; Medicine, Chinese Traditional ; Public Health ; Comorbidity ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients. METHODS: A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed. RESULTS: The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients. CONCLUSION In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.
Child ; Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Clinical Relevance ; Disease-Free Survival ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prednisone/therapeutic use* ; Prognosis ; Recurrence ; Immunoglobulin Light Chains, Surrogate/genetics*

OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m²·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.
Humans ; Aged ; Azacitidine/therapeutic use* ; Prospective Studies ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols ; Leukemia, Myeloid, Acute/etiology* ; Proto-Oncogene Proteins c-bcl-2