Dioscin alleviates aplastic anemia through regulatory T cells promotion.

Objectives: Aplastic anemia (AA) is one of the immune-mediated bone marrow failure disorders caused by multiple factors, including the inability of CD4 + CD25 + regulatory T cells (Tregs) to negatively regulate cytotoxic T lymphocytes (CTLs). Dioscin is a natural steroid saponin that has a similar structure to steroid hormones. The purpose of this study is to look into the effect of Dioscin on the functions of CD4 + CD25+ Tregs in the AA mouse model and explore its underlying mechanism.Methods: To begin with, bone marrow failure was induced through total body irradiation and allogeneic lymphocyte infusion using male Balb/c mice. After 14 consecutive days of Dioscin orally administrated, the AA mouse model was tested for complete blood counts, HE Staining of the femur, Foxp3, IL-10 and TGF-ß. Then CD4 + CD25+ Tregs were isolated from splenic lymphocytes of the AA mouse model, Tregs and the biomarkers and cytokines of Tregs were measured after 24 h of Dioscin intervention treatment in vitro.Results: Dioscin promotes the expression of Foxp3, IL-10, IL-35 and TGF-ß, indicating its Tregs-promoting properties. Mechanistically, the administration of Dioscin resulted in the alteration of CD152, CD357, Perforin and CD73 on the surface of Tregs, and restored the expression of Foxp3.Conclusion: Dioscin markedly attenuated bone marrow failure, and promoted Tregs differentiation, suggesting the maintenance of theimmune balance effect of Dioscin. Dioscin attenuates pancytopenia and bone marrow failure via its Tregs promotion properties.

Association Between Neutrophil-to-Lymphocyte Ratio and Benign Prostatic Hyperplasia: Results from the TCLSIH Cohort Study.

Purpose: The prevalence of benign prostatic hyperplasia (BPH) in the general Chinese adult male population has risen sharply over the past few decades. Increasing evidence suggests that inflammation plays an important role in the pathogenesis of BPH. To better understand the role of inflammation in the pathogenesis of BPH, we can use the neutrophil-to-lymphocyte ratio (NLR) because it is a simple and effective marker of inflammation and immunity. This study aims to prospectively investigate the association between NLR levels and the prevalence of BPH in a general Chinese adult male population. Patients and Methods: This study included a total of 15,783 male participants free from BPH at baseline. NLR was measured according to the complete blood count. BPH was defined as total prostate volume (TPV) ≥30 mL, and TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels. Results: During a median follow-up of 2.7 years, 5078 BPH cases were documented. After adjusting for age, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, and inflammation markers, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.08 (95% CIs 0.99, 1.17), 1.10 (95% CIs1.02, 1.19), and 1.12 (95% CIs1.03, 1.21), respectively, for participants with NLR in the first, second, third, and fourth quartiles (P for trend <0.01). Conclusion: Higher NLR levels were associated with a higher risk of BPH in Chinese adult male population. Our findings support the notion that NLR levels may be an important target for BPH prevention and intervention.

Association Between Mean Platelet Volume and Benign Prostatic Hyperplasia: A Population Study from the TCLSIH Cohort Study.

Purpose: This study aimed to prospectively investigate the association between mean platelet volume (MPV) levels and risk of benign prostatic hyperplasia (BPH) in a general Chinese adult male population, and assessed this association in metabolic syndrome (MetS) patients. Patients and methods: This study included a total of 14,923 male participants free from BPH at baseline. MPV was measured by the method of laser-based flow cytometric impedance according to the complete blood sample. BPH was defined as total prostate volume (TPV) ≥ 30 mL, TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels. Results: During a median follow-up of 2.7 years, 4848 BPH cases were documented in total male participants, and 1787 BPH cases were documented in MetS participants. After adjusting for age, body mass index, smoking, alcohol and personal and family history of disease, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.96, 1.11), 1.00 (95% CIs 0.92, 1.08) and 0.98 (95% CIs 0.90, 1.06), respectively, for participants with MPV in the 1st, 2nd, 3rd and 4th quartiles (P for trend = 0.47). In MetS patients, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.90, 1.16), 0.99 (95% CIs 0.87, 1.14) and 1.01 (95% CIs 0.89, 1.15) (P for trend= 0.98), respectively. Conclusion: A non-significant association was observed between MPV levels and risk of BPH, and no association in this association in MetS patients. Our findings support the notion that MPV levels may not be a target for BPH prevention and intervention.

Near-real-time daily estimates of fossil fuel CO2 emissions from major high-emission cities in China.

Cities in China are on the frontline of low-carbon transition which requires monitoring city-level emissions with low-latency to support timely climate actions. Most existing CO2 emission inventories lag reality by more than one year and only provide annual totals. To improve the timeliness and temporal resolution of city-level emission inventories, we present Carbon Monitor Cities-China (CMCC), a near-real-time dataset of daily CO2 emissions from fossil fuel and cement production for 48 major high-emission cities in China. This dataset provides territory-based emission estimates from 2020-01-01 to 2021-12-31 for five sectors: power generation, residential (buildings and services), industry, ground transportation, and aviation. CMCC is developed based on an innovative framework that integrates bottom-up inventory construction and daily emission estimates from sectoral activities and models. Annual emissions show reasonable agreement with other datasets, and uncertainty ranges are estimated for each city and sector. CMCC provides valuable daily emission estimates that enable low-latency mitigation monitoring for cities in China.

Dioscin Regulating Bone Marrow Apoptosis in Aplastic Anemia.

Background: Aplastic anemia (AA), a disease of bone marrow failure, is caused by CD8+T mediated apoptosis of hematopoietic cells. However, traditional immunosuppressive therapy (IST) has severe liver and kidney toxicity and even cannot achieve the expected therapeutic effect in some patients. Purpose: Our study is aimed to investigate the effect and mechanism of dioscin (DNS) for treating AA. Methods: Briefly, we established and evaluated the AA mouse model, DNS and positive control drugs were used for intervention treatment. After 14 days of intervention, femoral bone marrow pathology, bone marrow mononuclear cells (BMMCs) apoptosis rate, bone marrow CD34+ cell surface Fas (CD95) expression and Fas signaling pathway key proteins were detected. Results: After the establishment of the AA mouse model, the number of peripheral blood cells including granulocytes, erythrocytes, hemoglobin, platelets and reticulocytes in the AA group model was significantly decreased compared with the group control (P < 0.01). The degree of bone marrow hyperplasia in the sternum and femur is extremely low. After different drug interventions, compared with the group model, the number of peripheral blood cells in the AA mice rebounded significantly in group DNS (P < 0.01). Not only that the apoptosis rate of BM-MCs decreased (P < 0.01), meanwhile, the CD95 molecule expressed on the CD34+ bone marrow cells had a significant decline (P < 0.01), and the expression level of the key proteins of Fas signaling pathway was also significantly decreased (P < 0.01). Conclusion: DNS recovered the peripheral pancytopenia and bone marrow failure in AA mice. DNS reduced the key protein of Fas signaling pathway level to inhibit apoptosis of bone marrow cells to treat AA.

A mouse model of irradiation and spleen-thymus lymphocyte infusion induced aplastic anemia.

OBJECTIVES: The immune-induced aplastic anemia (AA) mouse model has been used for the study of AA. However, there were no uniform conditions for establishing a model and no assessment of immunological homeostasis. Our study aimed to identify the conditions of establishing a model and assess the AA model in immunology and pathology. METHODS: We induced an AA mouse model by the combination between sublethal irradiation and spleen-thymus lymphocyte infusion. The success of establishing the AA model was identified by blood routine tests and pathology of bone marrow. The frequency of Th17 and Treg cells was measured by flow cytometry. The frequency of CD34+ and CD41+ cells was detected by immunohistochemical technique.IL-6, IL-8, IL-17, TNF-α and IFN-γ were evaluated by ELISA. RESULTS: The 137Cs sublethal irradiation (5 Gy) and spleen-thymus lymphocyte infusion (5 × 106) induced the AA mouse model successfully. The AA mice had a long lifetime and manifested pancytopenia and bone marrow failure. The percentage of Th17 cells increased and the percentage of Treg cells decreased distinctly in AA mice. The area of hematopoietic tissues and count of CD34+ cells and CD41+ cells were significantly reduced in AA mice.The level of cytokines, IL-6, IL-8, IL-17, TNF-α and IFN-γ, was increased significantly in peripheral blood and bone marrow. CONCLUSION: Our data suggest that the improved AA mouse model conforms to the diagnosis standard of AA and simulates the immune internal environment of human AA. The AA mouse model has a longer lifetime and unbalances of Th17/Treg cells caused the destruction of CD34+ cells and CD41+ cells, which was immune-mediated pathogenesis to adapt to long-term research.

Machine Learning-Based MRI LAVA Dynamic Enhanced Scanning for the Diagnosis of Hilar Lesions.

OBJECTIVE: To explore the value of machine learning-based magnetic resonance imaging (MRI) liver acceleration volume acquisition (LAVA) dynamic enhanced scanning for diagnosing hilar lesions. METHODS: A total of 90 patients with hilar lesions and 130 patients without hilar lesions who underwent multiphase dynamic enhanced MRI LAVA were retrospectively selected as the study subjects. The 10-fold crossover method was used to establish the data set, 7/10 (154 cases) data were used to establish the training set, and 3/10 (66 cases) data were used to establish the validation set to verify the model. The region of interest was extracted from MRI images using radiomics, and the hilar lesion model was constructed based on a convolutional neural network. RESULTS: There were significant differences in respiration and pulse frequency between patients with hilar lesions and without hilar lesions (P <0.05). The subjective scores of the images in the first three phases of dynamic enhanced scanning in the training set were higher than those in the validation set (P < 0.05). There was no significant difference between the training and validation set in the last three phases of dynamic enhanced scanning. CONCLUSION: Machine learn-based MRI LAVA dynamic enhanced scanning for diagnosing hilar lesions has high diagnostic efficiency and can be used as an auxiliary diagnostic method.